TY - BOOK TI - Molecular and Biochemical Toxicology DA - 2018/// PY - 2018/// ET - 5th PB - J. Wiley and Sons ER - TY - BOOK TI - Molecular and Biochemical Toxicology A3 - Smart, R.C. A3 - Hodgson, E. DA - 2018/// PY - 2018/// ET - 5th PB - J. Wiley and Sons ER - TY - CHAP TI - Carcinogenesis AU - Smart, R.C. AU - Hall, J.R. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - CHAP TI - Molecular Techniques in the Study of Gene Function AU - Tsuji, Y. AU - Smart, R.C. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - CHAP TI - Molecular and Biochemical Toxicology: Definition and Scope AU - Smart, R.C. AU - Hodgson, E. T2 - Molecular and Biochemical Toxicology A2 - Smart, R.C. A2 - Hodgson, E. PY - 2018/// ET - 5th PB - J Wiley and Sons ER - TY - JOUR TI - The road less traveled: from genotype to phenotype in flies and humans AU - Anholt, Robert R. H. AU - Mackay, Trudy F. C. T2 - Mammalian Genome DA - 2018/2// PY - 2018/2// DO - 10.1007/S00335-017-9722-7 VL - 29 IS - 1-2 SP - 5–23 SN - 0938-8990 1432-1777 UR - http://dx.doi.org/10.1007/S00335-017-9722-7 ER - TY - CHAP TI - Cassava viruses – host jumps, virus recombination, spread in plant material AU - Mbewe, W. AU - Hanley-Bowdoin, L. AU - Ndunguru, J. AU - Duffy, S. T2 - Emerging Plant Diseases and Global Food Security A2 - Records, A. A2 - Ristaino, J. PY - 2018/// PB - APS Press ER - TY - JOUR TI - Role of the vacuolar ATPase in the Alphavirus replication cycle AU - Schuchman, Ryan M. AU - Vancini, Ricardo AU - Piper, Amanda AU - Breuer, Denitra AU - Ribeiro, Mariana AU - Ferreira, Davis AU - Magliocca, Joseph AU - Emmerich, Veronica AU - Hernandez, Raquel AU - Brown, Dennis T. T2 - Heliyon AB - We have shown that Alphaviruses can enter cells by direct penetration at the plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J Virol, 87:4352-4359, 2013). Direct penetration removes the requirement for receptor-mediated endocytosis exposure to low pH and membrane fusion in the process of RNA entry. Endosomal pH as well as the pH of the cell cytoplasm is maintained by the activity of the vacuolar ATPase (V-ATPase). Bafilomycin is a specific inhibitor of V-ATPase. To characterize the roll of the V-ATPase in viral replication we generated a Bafilomycin A1(BAF) resistant mutant of Sindbis virus (BRSV). BRSV produced mature virus and virus RNA in greater amounts than parent virus in BAF-treated cells. Sequence analysis revealed mutations in the E2 glycoprotein, T15I/Y18H, were responsible for the phenotype. These results show that a functional V-ATPase is required for efficient virus RNA synthesis and virus maturation in Alphavirus infection. DA - 2018/7// PY - 2018/7// DO - 10.1016/J.HELIYON.2018.E00701 VL - 4 IS - 7 SP - e00701 J2 - Heliyon LA - en OP - SN - 2405-8440 UR - http://dx.doi.org/10.1016/J.HELIYON.2018.E00701 DB - Crossref KW - Virology KW - Cell biology ER - TY - JOUR TI - A comprehensive genomic history of extinct and living elephants AU - Palkopoulou, Eleftheria AU - Lipson, Mark AU - Mallick, Swapan AU - Nielsen, Svend AU - Rohland, Nadin AU - Baleka, Sina AU - Karpinski, Emil AU - Ivancevic, Atma M. AU - To, Thu-Hien AU - Kortschak, R. Daniel AU - Raison, Joy M. AU - Qu, Zhipeng AU - Chin, Tat-Jun AU - Alt, Kurt W. AU - Claesson, Stefan AU - Dalén, Love AU - MacPhee, Ross D. E. AU - Meller, Harald AU - Roca, Alfred L. AU - Ryder, Oliver A. AU - Heiman, David AU - Young, Sarah AU - Breen, Matthew AU - Williams, Christina AU - Aken, Bronwen L. AU - Ruffier, Magali AU - Karlsson, Elinor AU - Johnson, Jeremy AU - Di Palma, Federica AU - Alfoldi, Jessica AU - Adelson, David L. AU - Mailund, Thomas AU - Munch, Kasper AU - Lindblad-Toh, Kerstin AU - Hofreiter, Michael AU - Poinar, Hendrik AU - Reich, David T2 - Proceedings of the National Academy of Sciences AB - Elephantids are the world's most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an ∼120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant's ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for ∼500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species. DA - 2018/2/26/ PY - 2018/2/26/ DO - 10.1073/PNAS.1720554115 VL - 115 IS - 11 SP - E2566-E2574 J2 - Proc Natl Acad Sci USA LA - en OP - SN - 0027-8424 1091-6490 UR - http://dx.doi.org/10.1073/PNAS.1720554115 DB - Crossref KW - paleogenomics KW - elephantid evolution KW - mammoth KW - admixture KW - species divergence ER - TY - JOUR TI - Growth kinetics of endosymbiont Wolbachia in the common bed bug, Cimex lectularius AU - Fisher, Michael L. AU - Watson, David W. AU - Osborne, Jason A. AU - Mochizuki, Hiroyuki AU - Breen, Matthew AU - Schal, Coby T2 - Scientific Reports AB - The common bed bug, Cimex lectularius harbors the endosymbiotic microorganism, Wolbachia (wCle), in a gonad-associated bacteriome as an obligate nutritional mutualist. The obligatory nature of this association suggests that all individuals in C. lectularius populations would be infected with wCle. However, studies spanning the past several decades have reported variation in both infection frequency and relative abundance of wCle in field-collected samples of bed bugs. Since the growth kinetics of wCle is poorly understood, the objective of this study was to quantify wCle over the life cycle of two strains of C. lectularius. Our results highlight that wCle is dynamic during bed bug development, changing relative to life stage, intermolt stage, and blood-fed status. These results suggest new hypotheses about the coordination of Wolbachia growth and regression with its host's physiology and endocrine events. The observed quantitative modulation of wCle during the bed bug life cycle and during periods of starvation may explain the disparities in wCle infections reported in field-collected C. lectularius. DA - 2018/7/30/ PY - 2018/7/30/ DO - 10.1038/S41598-018-29682-2 VL - 8 IS - 1 J2 - Sci Rep LA - en OP - SN - 2045-2322 UR - http://dx.doi.org/10.1038/S41598-018-29682-2 DB - Crossref ER - TY - JOUR TI - C/EBPβ deletion in oncogenic Ras skin tumors is a synthetic lethal event AU - Messenger, Zachary J. AU - Hall, Jonathan R. AU - Jima, Dereje D. AU - House, John S. AU - Tam, Hann W. AU - Tokarz, Debra A. AU - Smart, Robert C. T2 - Cell Death & Disease AB - Therapeutic targeting of specific genetic changes in cancer has proven to be an effective therapy and the concept of synthetic lethality has emerged. CCAAT/enhancer-binding protein-β (C/EBPβ), a basic leucine zipper transcription factor, has important roles in cellular processes including differentiation, inflammation, survival, and energy metabolism. Using a genetically engineered mouse model, we report that the deletion C/EBPβ in pre-existing oncogenic Ha-Ras mouse skin tumors in vivo resulted in rapid tumor regression. Regressing tumors exhibited elevated levels of apoptosis and p53 protein/activity, while adjacent C/EBPβ-deleted skin did not. These results indicate that the deletion of C/EBPβ de-represses p53 in oncogenic Ras tumors but not in normal wild-type Ras keratinocytes, and that C/EBPβ is essential for survival of oncogenic Ras tumors. Co-deletion of C/EBPβ and p53 in oncogenic Ras tumors showed p53 is required for tumor regression and elevated apoptosis. In tumors, loss of a pathway that confers adaptability to a stress phenotype of cancer/tumorigenesis, such as DNA damage, could result in selective tumor cell killing. Our results show that oncogenic Ras tumors display a significant DNA damage/replicative stress phenotype and these tumors have acquired a dependence on C/EBPβ for their survival. RNAseq data analysis of regressing tumors deleted of C/EBPβ indicates a novel interface between p53, type-1 interferon response, and death receptor pathways, which function in concert to produce activation of extrinsic apoptosis pathways. In summary, the deletion of C/EBPβ in oncogenic Ras skin tumors is a synthetic lethal event, making it a promising target for future potential anticancer therapies. DA - 2018/10/15/ PY - 2018/10/15/ DO - 10.1038/S41419-018-1103-Y VL - 9 IS - 11 J2 - Cell Death Dis LA - en OP - SN - 2041-4889 UR - http://dx.doi.org/10.1038/S41419-018-1103-Y DB - Crossref ER - TY - JOUR TI - Late blight of potato and tomato AU - Schumann, G. L. AU - D'Arcy, C. J. T2 - The Plant Health Instructor DA - 2018/// PY - 2018/// DO - 10.1094/PHI-I-2000-0724-01 SN - 1935-9411 UR - http://dx.doi.org/10.1094/PHI-I-2000-0724-01 ER - TY - JOUR TI - Cotton Leaf Curl Multan virus C4 protein suppresses both transcriptional and post-transcriptional gene silencing by interacting with SAM synthetase AU - Ismayil, Asigul AU - Haxim, Yakupjan AU - Wang, Yunjing AU - Li, Huangai AU - Qian, Lichao AU - Han, Ting AU - Chen, Tianyuan AU - Jia, Qi AU - Yihao Liu, Alexander AU - Zhu, Songbiao AU - Deng, Haiteng AU - Gorovits, Rena AU - Hong, Yiguo AU - Hanley-Bowdoin, Linda AU - Liu, Yule T2 - PLOS Pathogens AB - Gene silencing is a natural antiviral defense mechanism in plants. For effective infection, plant viruses encode viral silencing suppressors to counter this plant antiviral response. The geminivirus-encoded C4 protein has been identified as a gene silencing suppressor, but the underlying mechanism of action has not been characterized. Here, we report that Cotton Leaf Curl Multan virus (CLCuMuV) C4 protein interacts with S-adenosyl methionine synthetase (SAMS), a core enzyme in the methyl cycle, and inhibits SAMS enzymatic activity. By contrast, an R13A mutation in C4 abolished its capacity to interact with SAMS and to suppress SAMS enzymatic activity. Overexpression of wild-type C4, but not mutant C4R13A, suppresses both transcriptional gene silencing (TGS) and post-transcriptional gene silencing (PTGS). Plants infected with CLCuMuV carrying C4R13A show decreased levels of symptoms and viral DNA accumulation associated with enhanced viral DNA methylation. Furthermore, silencing of NbSAMS2 reduces both TGS and PTGS, but enhanced plant susceptibility to two geminiviruses CLCuMuV and Tomato yellow leaf curl China virus. These data suggest that CLCuMuV C4 suppresses both TGS and PTGS by inhibiting SAMS activity to enhance CLCuMuV infection in plants. DA - 2018/8/29/ PY - 2018/8/29/ DO - 10.1371/journal.ppat.1007282 VL - 14 IS - 8 SP - e1007282 J2 - PLoS Pathog LA - en OP - SN - 1553-7374 UR - http://dx.doi.org/10.1371/journal.ppat.1007282 DB - Crossref ER - TY - CONF TI - Track emerging late blight in the US and South America using a disease alert and surveillance systems and population genomics AU - Ristaino, JB AU - Restrepo, S T2 - AMER PHYTOPATHOLOGICAL SOC 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA C2 - 2018/// C3 - PHYTOPATHOLOGY DA - 2018/// VL - 108 M1 - 10 ER - TY - CONF TI - Archival Data and Text Analytics to Track 19th Century Late Blight AU - Ristaino, J AU - Yang, YP AU - Saville, AC AU - Guenter, R AU - Tateosian, L T2 - AMER PHYTOPATHOLOGICAL SOC 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA C2 - 2018/// C3 - PHYTOPATHOLOGY DA - 2018/// VL - 108 M1 - 10 ER - TY - JOUR TI - Molecular and Serological Prevalence of Anaplasma phagocytophilum, A. platys, Ehrlichia canis, E. chaffeenses, E. ewingii, Borrelia burgdorferi, Babesia canis, B. gibsoni and B. vogeli among Clinically Healthy Outdoor Dogs in Serbia AU - Kovačević Filipović, Milica M. AU - Beletić, Anđelo D. AU - Ilić Božović, Anja V. AU - Milanović, Zorana AU - Tyrrell, Phyllis AU - Buch, Jesse AU - Breitschwerdt, Edward B. AU - Birkenheuer, Adam J. AU - Chandrashekar, Ramaswamy T2 - Veterinary Parasitology: Regional Studies and Reports AB - Data concerning combined molecular and serological prevalence of emerging canine tick-borne pathogens in Serbia are lacking. A large population of outdoor living dogs in Belgrade, Serbia's' capital, present an excellent population for epidemiology study. Blood samples were collected from 111 dogs, including 46 shelter, 31 free roaming, and 34 hunting dogs. Species-specific real-time polymerase chain reaction (PCR) (IDEXX Laboratories, Inc., Westbrook Maine, USA) was applied for the molecular detection of Anaplasma phagocytophilum, A. platys, Ehrlichia canis, Babesia canis, B. gibsoni and B. vogeli. A research based SNAP assay (SNAP® M-A, IDEXX Laboratories, Inc., Westbrook Maine, USA) that uses genus and species-specific peptides was used to asses Anaplasma spp., A. phagocytophilum, A. platys, Ehrlichia spp., E. canis, E. chaffeensis, E. ewingii and Borrelia burgdorferi antibody status. B. canis, B. gibsoni and B. vogeli antibody status was assessed with an indirect immunofluorescence test (MegaCor Diagnostic, Horbranz, Austria). Anaplasma spp. and Ehrlichia spp. DNA was not amplified. One quarter of the dogs were A. phagocytophilum, one dog was A. platys, one was E. ewingii and two dogs were B. burgdorferi seroreactive with the SNAP® M-A. Babesia canis or B. gibsoni DNA was amplified by PCR from 16.2% of dogs, whereas 67.6% were seroreactive to one or more Babesia spp. Babesia vogeli was not PCR amplified. We conclude that outdoor dogs in this territory are reservoirs for B. canis and B. gibsoni and are frequently co-exposed to combinations of Anaplasma and Babesia spp. DA - 2018/12// PY - 2018/12// DO - 10.1016/j.vprsr.2018.10.001 VL - 14 SP - 117-122 J2 - Veterinary Parasitology: Regional Studies and Reports LA - en OP - SN - 2405-9390 UR - http://dx.doi.org/10.1016/j.vprsr.2018.10.001 DB - Crossref KW - Molecular prevalence KW - seroprevalence KW - Tick-borne pathogens KW - Dogs KW - Serbia ER - TY - JOUR TI - Bartonella spp. as a Possible Cause or Cofactor of Feline Endomyocarditis–Left Ventricular Endocardial Fibrosis Complex AU - Donovan, T.A. AU - Balakrishnan, N. AU - Carvalho Barbosa, I. AU - McCoy, T. AU - Breitschwerdt, E.B. AU - Fox, P.R. T2 - Journal of Comparative Pathology AB - Endomyocarditis is a commonly detected post-mortem finding in domestic cats presenting for sudden onset cardiovascular death, yet the aetiology remains unresolved. Cats are documented reservoir hosts for Bartonella henselae, the infectious cause of cat scratch disease in man. Various Bartonella spp. have been associated with culture-negative endocarditis, myocarditis and sudden death in man and animals. We hypothesized that Bartonella spp. DNA could be amplified more often from the hearts of cats with feline endomyocarditis-left ventricular endocardial fibrosis (FEMC-LVEF) complex compared with cats with hypertrophic cardiomyopathy (HCM) or cats with grossly and microscopically unremarkable hearts (designated non-cardiac disease controls). Formalin-fixed and paraffin wax-embedded, cardiac tissues from 60 domestic and purebred cats aged 3 months to 18 years were examined, and histological features were recorded. Cardiac tissue sections were tested for Bartonella DNA using multiple 16-23S intergenic transcribed spacer region polymerase chain reaction (PCR) primer sets, including two Bartonella genera, a Bartonella koehlerae species-specific and a Bartonella vinsonii subsp. berkhoffii-specific assay, followed by DNA sequence confirmation of the species or genotype. Special precautions were taken to avoid DNA cross-contamination between tissues. Bartonella spp. DNA was amplified by PCR and sequenced from 18 of 36 cats (50%) with FEMC-LVEF and 1/12 (8.3%) cats with HCM. Bartonella spp. DNA was not amplified from any non-cardiac disease control hearts. Based on PCR/DNA sequencing, one Bartonella spp. was amplified from 10 cats, while the remaining eight were coinfected with more than one Bartonella spp. To our knowledge, this study represents the first documentation of B. vinsonii subsp. berkhoffii genotype I infection in cats (n = 11). Fluorescence in-situ hybridization testing facilitated visualization of Bartonella bacteria within the myocardium of four of seven PCR-positive FEMC-LVEF hearts. Collectively, these findings support the hypothesis that Bartonella spp. may play a primary role or act as a cofactor in the pathogenesis of FEMC-LVEF. Studies involving cats from other geographical regions and definitive demonstration of Bartonella spp. within regions of inflammation are needed to confirm an association between Bartonella spp. and FEMC-LVEF induced morbidity and mortality in cats. DA - 2018/7// PY - 2018/7// DO - 10.1016/j.jcpa.2018.05.002 VL - 162 SP - 29-42 J2 - Journal of Comparative Pathology LA - en OP - SN - 0021-9975 UR - http://dx.doi.org/10.1016/j.jcpa.2018.05.002 DB - Crossref KW - Barlonella KW - cat KW - endocardial fibrosis KW - endomyocarditis ER - TY - JOUR TI - Using co-occurrence information and trait composition to understand individual plant performance in grassland communities AU - Breitschwerdt, Eva AU - Jandt, Ute AU - Bruelheide, Helge T2 - Scientific Reports AB - Depending on the strength of environmental filtering and competitive exclusion, successful colonizers of plant communities show varying degrees of similarity to resident species with respect to functional traits. For the present study, colonizer's performance was assessed in relation to the degree of fit with the resident community, and in addition, in relation to the community's trait profile and the environmental factors at the study locations. The two-year field experiment investigated the relative growth rates of 130 species that had been transplanted into German grassland communities varying in intensities of land-use. The transplanted species were selected in accordance with the following scenarios: species with highly similar or dissimilar traits to residents, species with highest degree of co-occurrence with resident species and species chosen randomly from the local species pool. The performance of transplanted phytometers depended on the scenario according to which the species were selected, on community trait diversity, and in addition, often on the interaction of both and on land use intensity. The total amount of explained variance in performance was low, but increased considerably when species identity was taken into account. In general, individuals in the co-occurrence scenario performed better than those selected based on trait information or those selected randomly. Different predictors were important in different seasons, demonstrating a limited temporal validity of performance models. DA - 2018/6/13/ PY - 2018/6/13/ DO - 10.1038/s41598-018-27017-9 VL - 8 IS - 1 J2 - Sci Rep LA - en OP - SN - 2045-2322 UR - http://dx.doi.org/10.1038/s41598-018-27017-9 DB - Crossref ER - TY - JOUR TI - Bartonella quintana and Bartonella vinsonii subsp. vinsonii bloodstream co-infection in a girl from North Carolina, USA AU - Breitschwerdt, Edward B. AU - Maggi, Ricardo G. T2 - Medical Microbiology and Immunology DA - 2018/9/24/ PY - 2018/9/24/ DO - 10.1007/s00430-018-0563-0 VL - 208 IS - 1 SP - 101-107 J2 - Med Microbiol Immunol LA - en OP - SN - 0300-8584 1432-1831 UR - http://dx.doi.org/10.1007/s00430-018-0563-0 DB - Crossref KW - Bartonella quintana KW - Bartonella vinsonii subsp KW - vinsonii KW - Bacteria KW - Vector KW - Equestrian ER - TY - JOUR TI - Mutational and transcriptomic profiling identify distinct angiogenic and inflammatory subtypes of angiosarcoma AU - Kim, Jong Hyuk AU - Megquier, Kate AU - Sarver, Aaron L. AU - Thomas, Rachael AU - Wang, Chao AU - Elvers, Ingegerd AU - Karlsson, Elinor AU - Breen, Matthew AU - Lindblad-Toh, Kerstin AU - Modiano, Jaime F. T2 - CANCER RESEARCH AB - Abstract Angiosarcoma is an aggressive, albeit rare cancer in humans. The cause of the vast majority of sporadic angiosarcomas is unknown, mortality is high, and no therapeutic targets have been identified to improve outcomes. Hemangiosarcoma (HSA) is a common cancer of dogs, and it shares histopathologic features with human angiosarcoma. In our previous work, canine HSAs were classified into angiogenic, inflammatory, and adipogenic subtypes based on transcriptional profiles. However, the genetic and molecular events that regulate transcriptional subtypes in angiosarcoma are not currently understood. Our goal was to use a comparative genomics approach to apply knowledge from appropriately powered canine studies to inform our research into human sarcomas. In this study, we identified recurrent mutations in RNASeq data from 93 HSAs and 16 nonmalignant controls, based on mutations first identified in exomes from 42 paired tumor and normal samples. In addition to identifying recurrent somatic mutations we also identified translocation fusions, allowing elucidation of oncogenic mechanisms for vascular endothelial growth factor receptors (VEGFR), phosphoinositide-3 kinase (PIK3) signaling pathways, and the p53 DNA damage repair pathway in canine HSA. Significantly, mutational signatures were associated with distinct molecular subtypes of canine hemangiosarcomas, and both the angiogenic and the inflammatory subtypes were apparent in RNASeq data from human angiosarcomas (n=14), suggesting that comparable etiologic mechanisms are operative in the canine and human disease. Our ongoing work seeks to understand how the molecular mechanisms give rise to molecular subtypes of angiosarcoma by defining the association between driver mutations, signaling pathway alterations and transcriptional patterns, which should allow us to identify rational therapeutic targets. Citation Format: Jong Hyuk Kim, Kate Megquier, Aaron L. Sarver, Rachael Thomas, Chao Wang, Ingegerd Elvers, Elinor Karlsson, Matthew Breen, Kerstin Lindblad-Toh, Jaime F. Modiano. Mutational and transcriptomic profiling identify distinct angiogenic and inflammatory subtypes of angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5357. DA - 2018/7// PY - 2018/7// DO - 10.1158/1538-7445.AM2018-5357 VL - 78 IS - 13 SP - SN - 1538-7445 ER - TY - JOUR TI - Comparative genomic analyses of osteosarcoma etiology reveal a chromosomal structural rationale for the increased incidence of osteosarcoma in dogs AU - Sarver, Aaron L. AU - Mills, Lauren AU - Temiz, Nuri AU - Scott, MIlcah AU - Sarver, Anne AU - Spector, Logan AU - Wang, Jinhua AU - Breen, Mathew AU - Subramanian, Subbaya AU - Moriarity, Branden AU - Modiano, Jaime AU - Largaespada, David T2 - CANCER RESEARCH AB - Abstract Risk of osteosarcoma is significantly higher in large and giant breed dogs than in any other animal, including humans. To identify the reason for this observation, we used a comparative genomic approach to identify aberrations responsible for osteosarcoma etiology in a Sleeping Beauty transposon-accelerated mouse model, in human patients, and in naturally occurring canine tumors, using RNA-Seq and exome paired tumor normal analyses. Fusions identified in Sleeping Beauty-mutagenized tumors revealed a role for Cdkn2a disruption in Trp53 signaling, and for numerous genes which cooperate with disrupted TrpP53 signaling, indicating the existence of many diverse routes to osteosarcoma tumor formation. Similarly, human tumors showed TP53 pathway disruption associated with a high level of diversity of additional driver mechanisms, supporting multiple independent routes to tumor formation. However, in the majority of canine tumors, observed TP53 pathway aberrations co-occurred with loss of both copies of the region containing the PTEN tumor suppressor. In human osteosarcoma, only heterozygous PTEN loss was observed, and in both humans and mice, PTEN aberration was observed in a much smaller percentage of the tumor population. We hypothesize that increased osteosarcoma incidence in dogs is partly due to a syntenic rearrangement of the peri-PTEN locus in the canine genome. The PTEN gene is part of a small synteny block that localized in the distal end of canine chromosome 26 (CFA 26) during evolution. We hypothesize that this location change creates a high risk of loss in the context of cytogenetic instability caused by disruption of TP53, thereby providing a structural genetic rational for the higher incidence of osteosarcoma in dogs. Consistent with these results and with the powerful nature of PTEN as a tumor suppressor, canine osteosarcomas with homozygous loss of PTEN are associated with worse outcomes than canine osteosarcomas with intact PTEN. These results suggest that engineering genomes to minimize cancer risk may be a realistic approach to the prevention of cancer. Citation Format: Aaron L. Sarver, Lauren Mills, Nuri Temiz, MIlcah Scott, Anne Sarver, Logan Spector, Jinhua Wang, Mathew Breen, Subbaya Subramanian, Branden Moriarity, Jaime Modiano, David Largaespada. Comparative genomic analyses of osteosarcoma etiology reveal a chromosomal structural rationale for the increased incidence of osteosarcoma in dogs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3399. DA - 2018/7// PY - 2018/7// DO - 10.1158/1538-7445.AM2018-3399 VL - 78 IS - 13 SP - SN - 1538-7445 ER - TY - JOUR TI - Sparse Polynomial Interpolation With Arbitrary Orthogonal Polynomial Bases AU - Imamoglu, Erdal AU - Kaltofen, Erich L. AU - Yang, Zhengfeng T2 - ISSAC'18: PROCEEDINGS OF THE 2018 ACM INTERNATIONAL SYMPOSIUM ON SYMBOLIC AND ALGEBRAIC COMPUTATION AB - An algorithm for interpolating a polynomial f from evaluation points whose running time depends on the sparsity t of the polynomial when it is represented as a sum of t Chebyshev Polynomials of the First Kind with non-zero scalar coefficients is given by Lakshman Y. N. and Saunders [SIAM J. Comput., vol. 24, nr. 2 (1995)]; Kaltofen and Lee [JSC, vol. 36, nr. 3--4 (2003)] analyze a randomized early termination version which computes the sparsity t. Those algorithms mirror Prony's algorithm for the standard power basis to the Chebyshev Basis of the First Kind. An alternate algorithm by Arnold's and Kaltofen's [Proc. ISSAC 2015, Sec. 4] uses Prony's original algorithm for standard power terms. Here we give sparse interpolation algorithms for generalized Chebyshev polynomials, which include the Chebyshev Bases of the Second, Third and Fourth Kind. Our algorithms also reduce to Prony's algorithm. If given on input a bound B >= t for the sparsity, our new algorithms deterministically recover the sparse representation in the First, Second, Third and Fourth Kind Chebyshev representation from exactly t + B evaluations. Finally, we generalize our algorithms to bases whose Chebyshev recurrences have parametric scalars. We also show how to compute those parameter values which optimize the sparsity of the representation in the corresponding basis, similar to computing a sparsest shift. DA - 2018/// PY - 2018/// DO - 10.1145/3208976.3208999 SP - 223-230 ER - TY - JOUR TI - Comparative Evaluation of 2 In-Clinic Assays for Vector-Borne Disease Testing in Dogs AU - Liu, Jiayou AU - Drexel, Jan AU - Andrews, Blaine AU - Eberts, Matt AU - Breitschwerdt, Ed AU - Chandrashekar, Ramaswamy T2 - TOPICS IN COMPANION ANIMAL MEDICINE AB - Vector-borne agents comprise medically important infections affecting dogs throughout much of the world. Sensitive detection of antibodies directed at tick-borne disease-causing organisms in dogs is diagnostically important for veterinarians, pets and their owners, and epidemiologically important for public health surveillance. The SNAP 4Dx Plus Test (IDEXX Laboratories, Inc., Westbrook, ME) identifies antibodies to or infection with multiple tick-borne pathogens and canine heartworm antigen in a single assay. Recently, VetScan FLEX4 Rapid Test (Abaxis, Inc., Union City, CA) was launched as a new assay to detect tick-borne pathogen antibodies and heartworm antigen. In the present study, we evaluated the comparative performance of SNAP 4Dx Plus (SNAP) and FLEX4 Rapid Test (FLEX4) using samples selected based on geographic distributions for canine vector borne diseases, including Borrelia burgdorferi (n = 105), Anaplasma phagocytophilum (160), Anaplasma platys (115), Ehrlichia canis (154), Ehrlichia ewingii (163), Ehrlichia chaffeensis (151) and Dirofilaria immitis (105). Canine vector borne diseases infection status was established for each sample by a combination of reference methods that included necropsy (D. immitis, heartworm disease), Western immunoblotting (B. burgdorferi), immunofluorescence assays (A. phagocytophilum and E. canis) and species-specific ELISAs (A. platys, E. canis, E. ewingii and E. chaffeensis). For comparisons among the 2 assays, samples were evaluated per the manufacturers' instructions for each test kit. By testing each same sample set compared to the defined reference results, sensitivities differed substantially between SNAP and FLEX4, at 95.5 vs. 40.9%, respectively for B. burgdorferi, 97.1% vs. 61.4% for E. canis, 98.2% vs. 59.3% for E. ewingii, 64.3% vs. 35.7% for E. chaffeensis, 84.5% vs. 12.7% for A. phagocytophilum, 83.3% vs. 33.3% for A. platys, and 94.1% vs. 88.2% for D. immitis. Specificities for both rapid assay tests ranged from 98% to 100%. Based upon the comparative results derived from this study, the SNAP test was more sensitive than the FLEX4 test for detection of antibodies to all tick-borne pathogens and heartworm disease (Dirofilaria immitis) antigen in dogs. DA - 2018/12// PY - 2018/12// DO - 10.1053/j.tcam.2018.09.003 VL - 33 IS - 4 SP - 114-118 SN - 1946-9837 KW - SNAP 4Dx plus KW - FLEX4 KW - tick-borne disease KW - heartworm disease KW - in-clinic assays KW - serology ER - TY - JOUR TI - Identification of Cytauxzoon felis antigens via protein microarray and assessment of expression library immunization against cytauxzoonosis AU - Schreeg, Megan E. AU - Marr, Henry S. AU - Tarigo, Jaime L. AU - Sherrill, Meredith K. AU - Outi, Hilton K. AU - Scholl, Elizabeth H. AU - Bird, David M. AU - Vigil, Adam AU - Hung, Chris AU - Nakajima, Rie AU - Liang, Li AU - Trieu, Angela AU - Doolan, Denise L. AU - Thomas, Jennifer E. AU - Levy, Michael G. AU - Reichard, Mason V. AU - Felgner, Philip L. AU - Cohn, Leah A. AU - Birkenheuer, Adam J. T2 - CLINICAL PROTEOMICS AB - Cytauxzoonosis is a disease of felids in North America caused by the tick-transmitted apicomplexan parasite Cytauxzoon felis. Cytauxzoonosis is particularly virulent for domestic cats, but no vaccine currently exists. The parasite cannot be cultivated in vitro, presenting a significant limitation for vaccine development.Recent sequencing of the C. felis genome has identified over 4300 putative protein-encoding genes. From this pool we constructed a protein microarray containing 673 putative C. felis proteins. This microarray was probed with sera from C. felis-infected and naïve cats to identify differentially reactive antigens which were incorporated into two expression library vaccines, one polyvalent and one monovalent. We assessed the efficacy of these vaccines to prevent of infection and/or disease in a tick-challenge model.Probing of the protein microarray resulted in identification of 30 differentially reactive C. felis antigens that were incorporated into the two expression library vaccines. However, expression library immunization failed to prevent infection or disease in cats challenged with C. felis.Protein microarray facilitated high-throughput identification of novel antigens, substantially increasing the pool of characterized C. felis antigens. These antigens should be considered for development of C. felis vaccines, diagnostics, and therapeutics. DA - 2018/12/29/ PY - 2018/12/29/ DO - 10.1186/s12014-018-9218-9 VL - 15 IS - 1 SP - SN - 1559-0275 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85059281263&partnerID=MN8TOARS KW - Cytauxzoonosis KW - Cytauxzoon felis KW - Expression library immunization KW - Protein microarray KW - Piroplasmid KW - Vaccine ER - TY - JOUR TI - Plant Virus-Based Nanoparticles for the Delivery of Agronomic Compounds as a Suspension Concentrate AU - Guenther, Richard H. AU - Lommel, Steven A. AU - Opperman, Charles H. AU - Sit, Tim L. T2 - VIRUS-DERIVED NANOPARTICLES FOR ADVANCED TECHNOLOGIES: METHODS AND PROTOCOLS AB - Nanoparticle formulations of agrichemicals may enhance their performance while simultaneously mitigating any adverse environmental effects. Red clover necrotic mosaic virus (RCNMV) is a soil-transmitted plant virus with many inherent attributes that allow it to function as a plant virus-based nanoparticle (PVN) when loaded with biologically active ingredients. Here we describe how to formulate a PVN loaded with the nematicide abamectin (Abm) beginning with the propagation of the virus through the formulation, deactivation, and characterization of the finished product. DA - 2018/// PY - 2018/// DO - 10.1007/978-1-4939-7808-3_13 VL - 1776 SP - 203-214 SN - 1940-6029 KW - Plant pathogenic nematode KW - Nematicide KW - Agrichemical KW - Plant viral nanoparticle KW - Nanoparticle formulation ER - TY - JOUR TI - Red and near-infrared fluorophores inspired by chlorophylls. Consideration of practical brightness in multicolor flow cytometry and biomedical sciences AU - Taniguchi, Masahiko AU - Hu, Gongfang AU - Liu, Rui AU - Du, Hai AU - Lindsey, Jonathan S. T2 - REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS X AB - Demands in flow cytometry for increased multiplexing (for detection of multiple antigens) and brightness (for detection of rare entities) require new fluorophores (i.e., “colors”) with spectrally distinct fluorescence outside the relatively congested visible spectral region. Flow cytometry fluorophores typically must function in aqueous solution upon bioconjugation and ideally should exhibit a host of photophysical features: (i) strong absorption, (ii) sizable Stokes shift, (iii) modest if not strong fluorescence, and (iv) narrow fluorescence band. Tandem dyes have long been pursued to achieve a large effective Stokes shift, increased brightness, and better control over the excitation and emission wavelengths. Here, the attractive photophysical features of chlorophylls and bacteriochlorophylls – Nature’s chosen photoactive pigments for photosynthesis – are described with regards to use in flow cytometry. A chlorophyll (or bacteriochlorophyll) constitutes an intrinsic tandem dye given the red (or near-infrared) fluorescence upon excitation in the higher energy ultraviolet (UV) or visible absorption bands (due to rapid internal conversion to the lowest energy state). Synthetic (bacterio)chlorins are available with strong absorption (near-UV molar absorption coefficient ε(λexc) ~105 M-1cm-1), modest fluorescence quantum yield (Φf = 0.05–0.30), and narrow fluorescence band (10–25 nm) tunable from 600–900 nm depending on synthetic design. The “relative practical brightness” is given by intrinsic brightness [ε(λexc) x Φf] times ηf, the fraction of the fluorescence band that is captured by an emission filter in a multicolor experiment. The spectroscopic features of (bacterio)chlorins are evaluated quantitatively to illustrate practical brightness for this novel class of fluorophores in a prospective 8-color panel. DA - 2018/// PY - 2018/// DO - 10.1117/12.2302709 VL - 10508 SP - SN - 1996-756X KW - Bacteriochlorophyll KW - Chlorophyll KW - Flow cytometry KW - Fluorophores KW - Multicolor KW - Near infrared KW - Stokes shift KW - Tandem dye ER - TY - JOUR TI - Genome sequence, metabolic properties and cyanobacterial attachment of Porphyrobacter sp. HT-58-2 isolated from a filamentous cyanobacterium–microbial consortium AU - Hughes, Rebecca-Ayme AU - Jin, Xiaohe AU - Zhang, Yunlong AU - Zhang, Ran AU - Tran, Sabrina AU - Williams, Philip G. AU - Lindsey, Jonathan S. AU - Miller, Eric S. T2 - Microbiology AB - Tolyporphins are structurally diverse tetrapyrrole macrocycles produced by the cyanobacterial culture HT-58-2. Although tolyporphins were discovered over 25 years ago, little was known about the microbiology of the culture. The studies reported herein expand the description of the community of predominantly alphaproteobacteria associated with the filamentous HT-58-2 cyanobacterium and isolate a dominant bacterium, Porphyrobacter sp. HT-58-2, for which the complete genome is established and growth properties are examined. Fluorescence in situ hybridization (FISH) analysis of the cyanobacterium–microbial community with a probe targeting the 16S rRNA of Porphyrobacter sp. HT-58-2 showed fluorescence emanating from the cyanobacterial sheath. Although genes for the biosynthesis of bacteriochlorophyll a (BChl a) are present in the Porphyrobacter sp. HT-58-2 genome, the pigment was not detected under the conditions examined, implying the absence of phototrophic growth. Comparative analysis of four Porphyrobacter spp. genomes from worldwide collection sites showed significant collinear gene blocks, with two inversions and three deletion regions. Taken together, the results enrich our understanding of the HT-58-2 cyanobacterium–microbial culture. DA - 2018/10/1/ PY - 2018/10/1/ DO - 10.1099/mic.0.000706 VL - 164 IS - 10 SP - 1229-1239 LA - en OP - SN - 1350-0872 1465-2080 UR - http://dx.doi.org/10.1099/mic.0.000706 DB - Crossref KW - alphaproteobacteria KW - fluorescence in situ hybridization (FISH) KW - tolyporphins KW - bacteriochlorin KW - photosynthetic gene cluster ER - TY - JOUR TI - Evaluation of cell culture-grown Bartonella antigens in immunofluorescent antibody assays for the serological diagnosis of bartonellosis in dogs AU - Neupane, Pradeep AU - Hegarty, Barbara C. AU - Marr, Henry S. AU - Maggi, Ricardo G. AU - Birkenheuer, Adam J. AU - Breitschwerdt, Edward B. T2 - Journal of Veterinary Internal Medicine AB - Background Because of poor sensitivity and questionable specificity of immunofluorescent antibody assays (IFAs), serological diagnosis of Bartonella species infections in dogs remains challenging. Despite limitations, IFA testing is the historical “gold standard” for Bartonella serodiagnosis in animals and humans. Because most diagnostic laboratories test against only 1 or 2 Bartonella spp., testing against a broader panel of Bartonella antigens may enhance diagnostic sensitivity and specificity. Objective To evaluate the sensitivity and specificity of Bartonella IFA using 8 cell culture‐grown Bartonella spp. isolates. Animals Archived serum samples from 34 Bartonella spp. naturally exposed, polymerase chain reaction (PCR)‐positive dogs and from 26 PCR‐negative and IFA‐negative dogs. Methods Bartonella IFA sensitivity and specificity were assessed using cell culture‐grown whole cell antigens derived from 3 Bartonella henselae ( Bh ) strains ( Bh Houston 1, Bh San Antonio Type 2 , Bh California 1), 3 Bartonella vinsonii subsp. berkhoffii genotypes ( Bvb I, II, and III), Bartonella koehlerae ( Bk ), and Bartonella quintana ( Bq ). Results Only 62% of 34 Bartonella spp. PCR‐positive dogs were seroreactive to any of the 8 Bartonella IFA antigens, indicating low IFA sensitivity. PCR‐positive dogs were most often IFA seroreactive to Bq ( n = 15), to Bvb II ( n = 13), or to both ( n = 9) antigens. Of the 26 previously IFA‐negative/PCR‐negative dogs, 4 (15%) were seroreactive using the expanded antigen panel. Conclusion and Clinical Importance Despite IFA testing of dogs against 8 different Bartonella isolates, IFA sensitivity remained poor, and specificity was only 85%. Development of a reliable serological assay is needed to facilitate the diagnosis of Bartonella infection in dogs. DA - 2018/10/11/ PY - 2018/10/11/ DO - 10.1111/jvim.15301 VL - 32 IS - 6 SP - 1958-1964 J2 - J Vet Intern Med LA - en OP - SN - 0891-6640 UR - http://dx.doi.org/10.1111/jvim.15301 DB - Crossref KW - bacteria KW - BAPGM KW - serology KW - vector-borne KW - zoonosis ER - TY - JOUR TI - Babesia gibsoni cytochrome b mutations in canine blood samples submitted to a US veterinary diagnostic laboratory AU - Birkenheuer, Adam J. AU - Marr, Henry S. AU - Wilson, James M. AU - Breitschwerdt, Edward B. AU - Qurollo, Barbara A. T2 - Journal of Veterinary Internal Medicine AB - Background: Babesiosis caused by Babesia gibsoni is recognized throughout the world and can be difficult to treat. Resistance to atovaquone is associated with mutations in the B. gibsoni mitochondrial genome, specifically the M128 position of cytochrome b ( cytb ). The prevalence of cytb mutations in North America has not been reported. Hypothesis/Objectives: The objective of our study was to describe the prevalence of cytb M128 mutations in B. gibsoni in canine blood samples submitted to a US veterinary diagnostic laboratory. A secondary objective was to determine whether or not some dogs had wild‐type cytb in our initial samples then had M128 mutations detected in follow‐up samples. Animals: One‐Hundred seventy‐four dogs that tested positive for the presence of B. gibsoni between 2012 and 2017. Methods: Case series of consecutive samples submitted to a veterinary diagnostic laboratory. Partial B. gibsoni cytb genes were amplified by polymerase chain reaction and screened for the presence of mutations at the M128 position. Results: The overall prevalence of M128 mutants was 3.5% (6/173 dogs) in the initial samples. The incidence of new cytb mutants in dogs that tested positive for B. gibsoni , which then had follow‐up testing, was 12.1% (5/41). Conclusions and Clinic Importance: Our study reaffirms that B. gibsoni infection is widespread and most commonly detected in American Staffordshire Terrier/American Pit Bull Terrier dogs (128/174, 74% of the infected dogs in our study). The prevalence of cytb mutations does not warrant pretreatment genotyping. DA - 2018/10/11/ PY - 2018/10/11/ DO - 10.1111/jvim.15300 VL - 32 IS - 6 SP - 1965-1969 J2 - J Vet Intern Med LA - en OP - SN - 0891-6640 UR - http://dx.doi.org/10.1111/jvim.15300 DB - Crossref KW - atovaquone KW - mitochondrial KW - pharmacogenomics KW - resistance ER - TY - JOUR TI - Genetic Variation in Water-Use Efficiency (WUE) and Growth in Mature Longleaf Pine AU - Castillo, Ana C. AU - Goldfarb, Barry AU - Johnsen, Kurt H. AU - Roberds, James H. AU - Nelson, C. Dana T2 - FORESTS AB - The genetic and physiological quality of seedlings is a critical component for longleaf pine (Pinus palustris Mill.) restoration, because planting genetic material that is adapted to environmental stress is required for long-term restoration success. Planting trees that exhibit high water-use efficiency (WUE) is a practice that could maximize this species’ survival and growth in a changing climate. Our study evaluates genetic variation in WUE and growth, as well as WUE-growth relationships, a key step to determine potential for breeding and planting trees with high WUE. We measured carbon isotope discrimination (∆)—a proxy for WUE—in 106 longleaf pine increment cores extracted from trees belonging to nine full-sib families. Tree diameter and total tree height were also measured at ages 7, 17, 30 and 40 years. Each increment core was divided into segments corresponding to ages 7–17, 18–30 and 31–40, representing early, intermediate and mature growth of the trees. We identified significant genetic variation in DBH and WUE among families that merit further exploration for identifying trees that can potentially withstand drought stress. Mean family growth rates were not associated with mean family values for carbon isotope discrimination. Family variation in both diameter growth and WUE but no relationship between family values for these traits, suggests it is possible to improve longleaf pines in both diameter growth and WUE through appropriate breeding. DA - 2018/11// PY - 2018/11// DO - 10.3390/f9110727 VL - 9 IS - 11 SP - SN - 1999-4907 KW - Pinus palustris KW - carbon isotope discrimination KW - family variation KW - climate change KW - reforestation ER - TY - JOUR TI - Bartonella infections in cats and dogs including zoonotic aspects AU - Álvarez-Fernández, Alejandra AU - Breitschwerdt, Edward B. AU - Solano-Gallego, Laia T2 - Parasites & Vectors AB - Bartonellosis is a vector-borne zoonotic disease with worldwide distribution that can infect humans and a large number of mammals including small companion animals (cats and dogs). In recent years, an increasing number of studies from around the world have reported Bartonella infections, although publications have predominantly focused on the North American perspective. Currently, clinico-pathological data from Europe are more limited, suggesting that bartonellosis may be an infrequent or underdiagnosed infectious disease in cats and dogs. Research is needed to confirm or exclude Bartonella infection as a cause of a spectrum of feline and canine diseases. Bartonella spp. can cause acute or chronic infections in cats, dogs and humans. On a comparative medical basis, different clinical manifestations, such as periods of intermittent fever, granulomatous inflammation involving the heart, liver, lymph nodes and other tissues, endocarditis, bacillary angiomatosis, peliosis hepatis, uveitis and vasoproliferative tumors have been reported in cats, dogs and humans. The purpose of this review is to provide an update and European perspective on Bartonella infections in cats and dogs, including clinical, diagnostic, epidemiological, pathological, treatment and zoonotic aspects. DA - 2018/12// PY - 2018/12// DO - 10.1186/s13071-018-3152-6 VL - 11 IS - 1 SP - J2 - Parasites Vectors LA - en OP - SN - 1756-3305 UR - http://dx.doi.org/10.1186/s13071-018-3152-6 DB - Crossref KW - Bartonella KW - Dog KW - Cat KW - Europe KW - Zoonosis ER - TY - JOUR TI - Chromatin structure profile data from DNS-seq: Differential nuclease sensitivity mapping of four reference tissues of B73 maize (Zea mays L) AU - Turpin, Zachary M. AU - Vera, Daniel L. AU - Savadel, Savannah D. AU - Lung, Pei-Yau AU - Wear, Emily E. AU - Mickelson-Young, Leigh AU - Thompson, William F. AU - Hanley-Bowdoin, Linda AU - Dennis, Jonathan H. AU - Zhang, Jinfeng AU - Bass, Hank W. T2 - DATA IN BRIEF AB - Presented here are data from Next-Generation Sequencing of differential micrococcal nuclease digestions of formaldehyde-crosslinked chromatin in selected tissues of maize (Zea mays) inbred line B73. Supplemental materials include a wet-bench protocol for making DNS-seq libraries, the DNS-seq data processing pipeline for producing genome browser tracks. This report also includes the peak-calling pipeline using the iSeg algorithm to segment positive and negative peaks from the DNS-seq difference profiles. The data repository for the sequence data is the NCBI SRA, BioProject Accession PRJNA445708. DA - 2018/10// PY - 2018/10// DO - 10.1016/j.dib.2018.08.015 VL - 20 SP - 358-363 SN - 2352-3409 ER - TY - JOUR TI - Unusual Stability of a Bacteriochlorin Electrocatalyst under Reductive Conditions. A Case Study on CO2 Conversion to CO AU - Jiang, Jianbing AU - Matula, Adam J. AU - Swierk, John R. AU - Romano, Neyen AU - Wu, Yueshen AU - Batista, Victor S. AU - Crabtree, Robert H. AU - Lindsey, Jonathan S. AU - Wang, Hailiang AU - Brudvig, Gary W. T2 - ACS CATALYSIS AB - Photosynthetic CO2 fixation is mediated by the enzyme RuBisCo, which employs a nonredox-active metal (Mg2+) to bind CO2 adjacent to an organic ligand that provides reducing equivalents for CO2 fixation. Attempts to use porphyrins as ligands in reductive catalysis have typically encountered severe stability issues owing to ligand reduction. Here, a synthetic zinc–bacteriochlorin is reported as an effective and robust electrocatalyst for CO2 reduction to CO with an overpotential of 330 mV, without undergoing porphyrin-like ligand degradation (or demetalation) even after prolonged bulk electrolysis. The reaction has a CO Faradaic efficiency of 92% and sustains a total current density of 2.3 mA/cm2 at −1.9 V vs Ag/AgCl. DFT calculations highlight the molecular origin of the observed stability and provide insights into catalytic steps. This bioinspired study opens avenues for the application of bacteriochlorin compounds for reductive electrocatalysis with extended life beyond that seen with porphyrin counterparts. DA - 2018/11// PY - 2018/11// DO - 10.1021/acscatal.8b02991 VL - 8 IS - 11 SP - 10131-10136 SN - 2155-5435 KW - bacteriochlorin KW - CO2 conversion KW - electrocatalysis KW - hydrogenation KW - porphyrin ER - TY - JOUR TI - Bartonella henselae in a dog with ear tip vasculitis AU - Southern, Brittany L. AU - Neupane, Pradeep AU - Ericson, Marna E. AU - Dencklau, Jamie C. AU - Linder, Keith E. AU - Bradley, Julie M. AU - McKeon, Gabriel P. AU - Long, Charles T. AU - Breitschwerdt, Edward B. T2 - Veterinary Dermatology AB - Background Bartonella henselae, a Gram‐negative, zoonotic, alpha‐proteobacteria has been previously implicated in association with cutaneous vasoproliferative lesions (bacillary angiomatosis), nodular panniculitis and multifocal erythema (erythema multiforme) in dogs. Objective Describe clinical, microbiological and histological lesions in a dog with ear margin vasculitis and B. henselae infection. Animals A 12‐month‐old, specific pathogen‐free intact female beagle dog maintained in a vector‐free laboratory animal resource facility. Methods and materials Bartonella and Rickettsia serological evaluation, Bartonella and Rickettsia PCR, Bartonella alpha‐proteobacteria growth medium (BAPGM) enrichment blood culture/PCR, histopathological investigation and confocal immunohistochemical evaluation. Results Serological investigation (seroreversion) and PCR testing of aural tissue biopsies failed to support Rickettsia rickettsii as a cause of the aural vasculitis; however, B. henselae, genotype San Antonio 2 DNA was amplified and sequenced from both ear tip margins and from normal‐appearing abdominal skin. Seroconversion to B. henselae was documented retrospectively by IFA testing. Bartonella henselae organisms were visualized by confocal immunostaining within all three biopsies. Histopathology revealed small vessel necrotizing vasculitis and dermal necrosis. Bartonella henselae s eroreversion and complete resolution of skin lesions occurred in conjunction with administration of oral doxycycline and enrofloxacin for six weeks. Conclusions and Clinical Importance Bartonella henselae is an emerging zoonotic pathogen that has been associated with leucocytoclastic vasculitis in humans and may have had a contributing or causative role in the development of the cutaneous aural margin vasculitis in this beagle. DA - 2018/10/14/ PY - 2018/10/14/ DO - 10.1111/vde.12695 VL - 29 IS - 6 SP - 537-e180 J2 - Vet Dermatol LA - en OP - SN - 0959-4493 UR - http://dx.doi.org/10.1111/vde.12695 DB - Crossref ER - TY - JOUR TI - A Risk Analysis of Precision Agriculture Technology to Manage Tomato Late Blight AU - Liu, Yangxuan AU - Langemeier, Michael R. AU - Small, Ian M. AU - Joseph, Laura AU - Fry, William E. AU - Ristaino, Jean B. AU - Saville, Amanda AU - Gramig, Benjamin M. AU - Preckel, Paul V. T2 - SUSTAINABILITY AB - Precision agriculture technology can transform farming related data into useful information, which may lead to more efficient usage of agricultural resources and increase sustainability. This paper compares precision agriculture technology with traditional practices in scheduling fungicide application so as to manage late blight disease in tomato production. The following three fungicide scheduling strategies were evaluated: a calendar-based strategy, the BlightPro Decision Support System based strategy (DSS-based strategy), and a strategy that does not involve fungicide application. The data from field trials and computer simulation experiments were used to construct distributions of the net return per acre for the calendar-based and the DSS-based strategies. These distributions were then compared using three standard approaches to ranking risky alternatives, namely: stochastic dominance, stochastic dominance with respect to a function, and stochastic efficiency with respect to a function. Assuming no yield differences between the calendar-based and the DSS-based strategies, the calendar-based strategy was preferred for highly late blight susceptible cultivars, and the DSS-based strategy was preferred for moderately susceptible and moderately resistant cultivars. Assuming no yield differences, the value of the BlightPro Decision Support System ranged from −$28 to $48 per acre. With the yield improvement for the DSS-based strategy included, the DSS-based strategy was preferred for the cultivars in all of the disease-resistance categories with the value ranging from $496 to $1714 per acre. DA - 2018/9// PY - 2018/9// DO - 10.3390/su10093108 VL - 10 IS - 9 SP - SN - 2071-1050 KW - risk analysis KW - tomato KW - precision agriculture KW - stochastic dominance KW - stochastic efficiency with respect to a function KW - disease management KW - late blight KW - decision support system ER - TY - JOUR TI - Diacylglycerol acyltransferase 1 is activated by phosphatidate and inhibited by SnRK1-catalyzed phosphorylation AU - Caldo, Kristian Mark P. AU - Shen, Wei AU - Xu, Yang AU - Hanley-Bowdoin, Linda AU - Chen, Guanqun AU - Weselake, Randall J. AU - Lemieux, M. Joanne T2 - PLANT JOURNAL AB - Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final and committed step in the Kennedy pathway for triacylglycerol (TAG) biosynthesis and, as such, elucidating its mode of regulation is critical to understand the fundamental aspects of carbon metabolism in oleaginous crops. In this study, purified Brassica napus diacylglycerol acyltransferase 1 (BnaDGAT1) in n-dodecyl-β-d-maltopyranoside micelles was lipidated to form mixed micelles and subjected to detailed biochemical analysis. The degree of mixed micelle fluidity appeared to influence acyltransferase activity. BnaDGAT1 exhibited a sigmoidal response and eventual substrate inhibition with respect to increasing concentrations of oleoyl-CoA. Phosphatidate (PA) was identified as a feed-forward activator of BnaDGAT1, enabling the final enzyme in the Kennedy pathway to adjust to the incoming flow of carbon leading to TAG. In the presence of PA, the oleoyl-CoA saturation plot became more hyperbolic and desensitized to substrate inhibition indicating that PA facilitates the transition of the enzyme into the more active state. PA may also relieve possible autoinhibition of BnaDGAT1 brought about by the N-terminal regulatory domain, which was shown to interact with PA. Indeed, PA is a key effector modulating lipid homeostasis, in addition to its well recognized role in lipid signaling. BnaDGAT1 was also shown to be a substrate of the sucrose non-fermenting-1-related kinase 1 (SnRK1), which catalyzed phosphorylation of the enzyme and converted it to a less active form. Thus, this known regulator of carbon metabolism directly influences TAG biosynthesis. DA - 2018/10// PY - 2018/10// DO - 10.1111/tpj.14029 VL - 96 IS - 2 SP - 287-299 SN - 1365-313X KW - triacylglycerol biosynthesis KW - DGAT KW - Brassica napus KW - biochemical regulation KW - allostery ER - TY - JOUR TI - Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles AU - Dumont, Beth L. AU - Williams, Christina L. AU - Ng, Bee Ling AU - Horncastle, Valerie AU - Chambers, Carol L. AU - McGraw, Lisa A. AU - Adams, David AU - Mackay, Trudy F. C. AU - Breen, Matthew T2 - GENETICS AB - In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles (Microtus) to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (Microtus montanus), never (Microtus mogollonensis), and occasionally synapse (Microtus ochrogaster) at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, M. montanus Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles. DA - 2018/9// PY - 2018/9// DO - 10.1534/genetics.118.301182 VL - 210 IS - 1 SP - 83-97 SN - 1943-2631 KW - pseudoautosomal region KW - Microtus heterochromatin KW - telomeric repeats KW - meiotic synapsis ER - TY - JOUR TI - Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis AU - Hendricks, William P. D. AU - Zismann, Victoria AU - Sivaprakasam, Karthigayini AU - Legendre, Christophe AU - Poorman, Kelsey AU - Tembe, Waibhav AU - Perdigones, Nieves AU - Kiefer, Jeffrey AU - Liang, Winnie AU - DeLuca, Valerie AU - Stark, Mitchell AU - Ruhe, Alison AU - Froman, Roe AU - Duesbery, Nicholas S. AU - Washington, Megan AU - Aldrich, Jessica AU - Neff, Mark W. AU - Huentelman, Matthew J. AU - Hayward, Nicholas AU - Brown, Kevin AU - Thamm, Douglas AU - Post, Gerald AU - Khanna, Chand AU - Davis, Barbara AU - Breen, Matthew AU - Sekulic, Alexander AU - Trent, Jeffrey M. T2 - PLOS GENETICS AB - Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species. DA - 2018/9// PY - 2018/9// DO - 10.1371/journal.pgen.1007589 VL - 14 IS - 9 SP - SN - 1553-7404 ER - TY - JOUR TI - Sucrose Nonfermenting 1-Related Protein Kinase 1 Phosphorylates a Geminivirus Rep Protein to Impair Viral Replication and Infection AU - Shen, Wei AU - Bobay, Benjamin G. AU - Greeley, Laura A. AU - Reyes, Maria I. AU - Rajabu, Cyprian A. AU - Blackburn, R. Kevin AU - Dallas, Mary Beth AU - Goshe, Michael B. AU - Ascencio-Ibanez, Jose T. AU - Hanley-Bowdoin, Linda T2 - PLANT PHYSIOLOGY AB - Geminiviruses are single-stranded DNA viruses that infect a wide variety of plants and cause severe crop losses worldwide. The geminivirus replication initiator protein (Rep) binds to the viral replication origin and catalyzes DNA cleavage and ligation to initiate rolling circle replication. In this study, we found that the Tomato golden mosaic virus (TGMV) Rep is phosphorylated at serine-97 by sucrose nonfermenting 1-related protein kinase 1 (SnRK1), a master regulator of plant energy homeostasis and metabolism. Phosphorylation of Rep or the phosphomimic S97D mutation impaired Rep binding to viral DNA. A TGMV DNA-A replicon containing the Rep S97D mutation replicated less efficiently in tobacco (Nicotiana tabacum) protoplasts than in wild-type or Rep phosphorylation-deficient replicons. The TGMV Rep-S97D mutant also was less infectious than the wild-type virus in Nicotiana benthamiana and was unable to infect tomato (Solanum lycopersicum). Nearly all geminivirus Rep proteins have a serine residue at the position equivalent to TGMV Rep serine-97. SnRK1 phosphorylated the equivalent serines in the Rep proteins of Tomato mottle virus and Tomato yellow leaf curl virus and reduced DNA binding, suggesting that SnRK1 plays a key role in combating geminivirus infection. These results established that SnRK1 phosphorylates Rep and interferes with geminivirus replication and infection, underscoring the emerging role for SnRK1 in the host defense response against plant pathogens. DA - 2018/9// PY - 2018/9// DO - 10.1104/pp.18.00268 VL - 178 IS - 1 SP - 372-389 SN - 1532-2548 ER - TY - JOUR TI - Distribution and risk factors associated with Babesia spp. infection in hunting dogs from Southern Italy AU - Veneziano, Vincenzo AU - Piantedosi, Diego AU - Ferrari, Nicola AU - Neola, Benedetto AU - Santoro, Mario AU - Pacifico, Laura AU - Sgroi, Giovanni AU - D'Alessio, Nicola AU - Panico, Tullio AU - Leutenegger, Christian M. AU - Tyrrell, Phyllis AU - Buch, Jesse AU - Breitschwerdt, Edward B. AU - Chandrashekar, Ramaswamy T2 - TICKS AND TICK-BORNE DISEASES AB - Canine babesiosis is caused by haemoprotozoan organisms of the genus Babesia which are transmitted by the bite of a hard tick. The aim of this survey was to determine the prevalence and risk factors associated with Babesia species infections in hunting dogs from Southern Italy. Blood samples were collected from 1311 healthy dogs in the Napoli, Avellino and Salerno provinces of the Campania region of Southern Italy. Serological testing was performed using two enzyme-linked immunosorbent assays (ELISA), with one designed to detect B. canis and B. vogeli antibodies, and the other designed to detect B. gibsoni antibodies. Blood samples were also tested by quantitative real-time polymerase chain reaction (qPCR) assays for amplification of B. canis, B. vogeli and B. gibsoni DNA. The overall seroprevalence for B. canis/B. vogeli was 14.0%, compared to 0.2% for B. gibsoni. B. canis and B. vogeli PCR positive rates were 0.15% and 1.1%, respectively. B. gibsoni DNA was not amplified by qPCR. Male gender (OR 1.85), increased age (OR 1.01), long hair coat (OR 1.61) and living in Salerno province (OR 1.71) represented risk factors for B. canis/B. vogeli seroreactivity. Hunting dogs in Southern Italy are often exposed to B. canis/B. vogeli, however Babesia spp. infection was infrequently detected using qPCR. Further studies are needed to determine the extent to which Babesia spp. cause clinical disease in hunting dogs, and to evaluate the potential epidemiological relationships between hunting dogs and wild animal populations sharing the same area. DA - 2018/9// PY - 2018/9// DO - 10.1016/j.ttbdis.2018.07.005 VL - 9 IS - 6 SP - 1459-1463 SN - 1877-9603 KW - Babesia canis KW - Babesia vogeli KW - Babesia gibsoni KW - Hunting dogs KW - Italy ER - TY - JOUR TI - Origin of Panchromaticity in Multichromophore-Tetrapyrrole Arrays AU - Yuen, Jonathan M. AU - Diers, James R. AU - Alexy, Eric J. AU - Roy, Arpita AU - Mandal, Amit Kumar AU - Kang, Hyun Suk AU - Niedzwiedzki, Dariusz M. AU - Kirmaier, Christine AU - Lindsey, Jonathan S. AU - Bocian, David F. AU - Holten, Dewey T2 - JOURNAL OF PHYSICAL CHEMISTRY A AB - Panchromatic absorbers that have robust photophysical properties enable new designs for molecular-based light-harvesting systems. Herein, we report experimental and theoretical studies of the spectral, redox, and excited-state properties of a series of perylene-monoimide–ethyne–porphyrin arrays wherein the number of perylene-monoimide units is stepped from one to four. In the arrays, a profound shift of absorption intensity from the strong violet-blue (By and Bx) bands of typical porphyrins into the green, red, and near-infrared (Qx and Qy) regions stems from mixing of chromophore and tetrapyrrole molecular orbitals (MOs), which gives multiplets of MOs having electron density spread over the entire array. This reduces the extensive mixing between porphyrin excited-state configurations and the transition-dipole addition and subtraction that normally leads to intense B and weak Q bands. Reduced configurational mixing derives from moderate effects of the ethyne and perylene on the MO energies and a more substantial effect of electron-density delocalization to reduce the configuration-interaction energy. Quantitative oscillator-strength analysis shows that porphyrin intensity is also shifted into the perylene-like green-region absorption and that the ethyne linkers lend absorption intensity. The reduced porphyrin configurational mixing also endows the S1 state with bacteriochlorin-like properties, including a 1–5 ns lifetime. DA - 2018/9/13/ PY - 2018/9/13/ DO - 10.1021/acs.jpca.8b06815 VL - 122 IS - 36 SP - 7181-7201 SN - 1089-5639 ER - TY - JOUR TI - Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins - diverse macrocycles, unrealized opportunities AU - Liu, Yizhou AU - Zhang, Shaofei AU - Lindsey, Jonathan S. T2 - NATURAL PRODUCT REPORTS AB - Quantitative evaluation of reported routes toward bonellin, chlorophylla, and tolyporphin A suggests heuristics for practical syntheses of native hydroporphyrins. DA - 2018/9/1/ PY - 2018/9/1/ DO - 10.1039/c8np00020d VL - 35 IS - 9 SP - 879-901 SN - 1460-4752 ER - TY - JOUR TI - Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals AU - Morgante, Fabio AU - Huang, Wen AU - Maltecca, Christian AU - Mackay, Trudy F. C. T2 - HEREDITY AB - Predicting complex phenotypes from genomic data is a fundamental aim of animal and plant breeding, where we wish to predict genetic merits of selection candidates; and of human genetics, where we wish to predict disease risk. While genomic prediction models work well with populations of related individuals and high linkage disequilibrium (LD) (e.g., livestock), comparable models perform poorly for populations of unrelated individuals and low LD (e.g., humans). We hypothesized that low prediction accuracies in the latter situation may occur when the genetics architecture of the trait departs from the infinitesimal and additive architecture assumed by most prediction models. We used simulated data for 10,000 lines based on sequence data from a population of unrelated, inbred Drosophila melanogaster lines to evaluate this hypothesis. We show that, even in very simplified scenarios meant as a stress test of the commonly used Genomic Best Linear Unbiased Predictor (G-BLUP) method, using all common variants yields low prediction accuracy regardless of the trait genetic architecture. However, prediction accuracy increases when predictions are informed by the genetic architecture inferred from mapping the top variants affecting main effects and interactions in the training data, provided there is sufficient power for mapping. When the true genetic architecture is largely or partially due to epistatic interactions, the additive model may not perform well, while models that account explicitly for interactions generally increase prediction accuracy. Our results indicate that accounting for genetic architecture can improve prediction accuracy for quantitative traits. DA - 2018/6// PY - 2018/6// DO - 10.1038/s41437-017-0043-0 VL - 120 IS - 6 SP - 500-514 SN - 1365-2540 ER - TY - JOUR TI - Characterization of Nicotiana tabacum genotypes possessing deletion mutations that affect potyvirus resistance and the production of trichome exudates AU - Dluge, Kurtis L. AU - Song, Zhongbang AU - Wang, Bingwu AU - Steede, W. Tyler AU - Xiao, Bingguang AU - Liu, Yong AU - Dewey, Ralph E. T2 - BMC GENOMICS AB - Advances in genomics technologies are making it increasingly feasible to characterize breeding lines that carry traits of agronomic interest. Tobacco germplasm lines that carry loci designated VAM and va have been extensively investigated due to their association with potyvirus resistance (both VAM and va) and defects in leaf surface compounds originating from glandular trichomes (VAM only). Molecular studies and classical genetic analyses are consistent with the model that VAM and va represent deletion mutations in the same chromosomal region. In this study, we used RNA-seq analysis, together with emerging tobacco reference genome sequence information to characterize the genomic regions deleted in tobacco lines containing VAM and va. Tobacco genotypes TI 1406 (VAM), K326-va and K326 (wild type) were analyzed using RNA-seq to generate a list of genes differentially expressed in TI 1406 and K326-va, versus the K326 control. Candidate genes were localized onto tobacco genome scaffolds and validated as being absent in only VAM, or missing in both VAM and va, through PCR analysis. These results enabled the construction of a map that predicted the relative extent of the VAM and va mutations on the distal end of chromosome 21. The RNA-seq analyses lead to the discovery that members of the cembratrienol synthase gene family are deleted in TI 1406. Transformation of TI 1406 with a cembratrienol synthase cDNA, however, did not recover the leaf chemistry phenotype. Common to both TI 1406 and K326-va was the absence of a gene encoding a specific isoform of a eukaryotic translation initiation factor (eiF4E1.S). Transformation experiments showed that ectopic expression of eiF4E1.S is sufficient to restore potyvirus susceptibility in plants possessing either the va or VAM mutant loci. We have demonstrated the feasibility of using RNA-seq and emerging whole genome sequence resources in tobacco to characterize the VAM and va deletion mutants. These results lead to the discovery of genes underlying some of the phenotypic traits associated with these historically important loci. Additionally, initial size estimations were made for the deleted regions, and dominant markers were developed that are very close to one of the deletion junctions that defines va. DA - 2018/6/20/ PY - 2018/6/20/ DO - 10.1186/s12864-018-4839-y VL - 19 SP - SN - 1471-2164 KW - Nicotiana tabacum KW - VAM KW - Va KW - Trichome exudate ER - TY - JOUR TI - Pathogenicity of Neonectria fuckeliana on Norway Spruce Clones in Sweden and Potential Management Strategies AU - Pettersson, Martin AU - Talgo, Venche AU - Frampton, John AU - Karlsson, Bo AU - Ronnberg, Jonas T2 - FORESTS AB - The fungus Neonectria fuckeliana has become an increasing problem on Norway spruce (Picea abies) in the Nordic countries during recent years. Canker wounds caused by the pathogen reduce timber quality and top-dieback is a problem for the Christmas tree industry. In this study, four inoculation trials were conducted to examine the ability of N. fuckeliana to cause disease on young Norway spruce plants and determine how different wound types would affect the occurrence and severity of the disease. Symptom development after 8–11 months was mainly mild and lesion lengths under bark were generally minor. However, N. fuckeliana could still be reisolated and/or molecularly detected. Slow disease development is in line with older studies describing N. fuckeliana as a weak pathogen. However, the results do not explain the serious increased damage by N. fuckeliana registered in Nordic forests and Christmas tree plantations. Potential management implications, such as shearing Christmas trees during periods of low inoculum pressure, cleaning secateurs between trees, and removal and burning of diseased branches and trees to avoid inoculum transfer and to keep disease pressure low, are based on experiments presented here and experiences with related pathogens. DA - 2018/3// PY - 2018/3// DO - 10.3390/f9030105 VL - 9 IS - 3 SP - SN - 1999-4907 KW - Picea abies KW - Nordic countries KW - canker KW - microconidia KW - inoculation KW - lesion length KW - infection ER - TY - JOUR TI - Ortet Age and Clonal Effects on Growth and Market Value of Fraser Fir (Abies fraseri) Grafts as Christmas Trees AU - Hinesley, Eric AU - Frampton, John AU - Deal, Buddy AU - Deal, Earl T2 - FORESTS AB - Grafting provides a means to clonally produce Fraser fir (Abies fraseri (Pursh) Poir.) Christmas trees that have desirable traits such as faster growth, greater crown density, increased pest resistance, or more desirable foliage attributes than seedling stock. Grafting Fraser fir to disease resistant rootstocks also provides a means to ameliorate the impact of root rot, predominantly caused by Phytophthora cinnamomi Rands. The influence of ortet age on growth and market value of grafts has not been studied for Fraser fir Christmas tree production. A field trial was established in 2004 near Independence, Virginia (USA), with the objectives of assessing (1) the effect of ortet age (stock plants = 6 to 8, 10 to 12, and 18 to 20 years) and (2) shearing regimes (fixed leader length versus variable leader length) on growth, quality, and market value of Fraser fir Christmas trees. Commercial height, Christmas tree grade (based on U. S. Dept. of Agric. standards), and net present value (US dollars) were assessed at the time of harvest. Cone damage to quality was rated after 8 years in the field. Scions from Fraser fir Christmas trees 2 m or taller produced grafts that expressed maturation, resulting in lower tree quality, heavier cone damage, and decreased market value compared to seedling stock. In contrast, the quality and market value of grafts was similar to that of seedlings when scions were collected from young Fraser fir Christmas trees. For Christmas tree production, scions should be collected from the upper whorls of trees no older than 2 to 3 years in the field (6 to 8 years from seed). The effect of age on Fraser fir clones varies so that pre-screening might identify some older selections suitable for use as scion donors. Fixed versus variable shearing regimes had little effect on tree value, although some individual clones responded better to one regime or the other. DA - 2018/4// PY - 2018/4// DO - 10.3390/f9040182 VL - 9 IS - 4 SP - SN - 1999-4907 KW - grafting KW - ortet KW - ramet KW - vegetative propagation KW - shearing KW - Christmas tree grade KW - cone crop KW - scion material ER - TY - JOUR TI - Molecular surveillance of novel tick-borne organisms in Madagascar's lemurs AU - Qurollo, Barbara A. AU - Larsen, Peter A. AU - Rakotondrainibe, Hajanirina H. AU - Mahefarisoa, Karine AU - Rajaonarivelo, Tsiky AU - Razafindramanana, Josia AU - Breitschwerdt, Edward B. AU - Junge, Randall E. AU - Williams, Cathy V. T2 - TICKS AND TICK-BORNE DISEASES AB - The discovery and characterization of emerging tick-borne organisms are critical for global health initiatives to improve animal and human welfare (One Health). It is possible that unknown tick-borne organisms underlie a subset of undiagnosed illness in wildlife, domesticated species, and humans. Our study lends support to the One Health concept by highlighting the prevalence of three blood-borne organisms in wild lemurs living in close proximity to domesticated species and humans. Previously, our team identified three novel, presumably tick-borne, intravascular organisms, belonging to the genera Babesia, Borrelia, and Neoehrlichia, circulating in two of Madagascar's lemur species. Here, we extend our previous observation by developing a targeted molecular surveillance approach aimed at determining the prevalence of these organisms in lemurs. Using quantitative PCR, we provide Babesia, Borrelia, and Neoehrlichia prevalence data for 76 individuals comprising four lemur species located in eastern Madagascar. Our results indicate a high prevalence (96%) of Babesia across sampled individuals with lower prevalences for Neoehrlichia (36%) and Borrelia (14.5%). In light of our results, we recommend additional studies of these tick-borne organisms to determine pathogenicity and assess zoonotic potency to other animals and humans in Madagascar. DA - 2018/3// PY - 2018/3// DO - 10.1016/j.ttbdis.2018.02.012 VL - 9 IS - 3 SP - 672-677 SN - 1877-9603 KW - Babesia KW - Borrelia KW - Neoehrlichia KW - Lemurs KW - Madagascar KW - One health ER - TY - JOUR TI - Lanai: A small, fast growing tomato variety is an excellent model system for studying geminiviruses AU - Rajabu, C. A. AU - Kennedy, G. G. AU - Ndunguru, J. AU - Ateka, E. M. AU - Tairo, F. AU - Hanley-Bowdoin, L. AU - Ascencio-Ibanez, J. T. T2 - JOURNAL OF VIROLOGICAL METHODS AB - Geminiviruses are devastating single-stranded DNA viruses that infect a wide variety of crops in tropical and subtropical areas of the world. Tomato, which is a host for more than 100 geminiviruses, is one of the most affected crops. Developing plant models to study geminivirus-host interaction is important for the design of virus management strategies. In this study, “Florida Lanai” tomato was broadly characterized using three begomoviruses (Tomato yellow leaf curl virus, TYLCV; Tomato mottle virus, ToMoV; Tomato golden mosaic virus, TGMV) and a curtovirus (Beet curly top virus, BCTV). Infection rates of 100% were achieved by agroinoculation of TYLCV, ToMoV or BCTV. Mechanical inoculation of ToMoV or TGMV using a microsprayer as well as whitefly transmission of TYLCV or ToMoV also resulted in 100% infection frequencies. Symptoms appeared as early as four days post inoculation when agroinoculation or bombardment was used. Symptoms were distinct for each virus and a range of features, including plant height, flower number, fruit number, fruit weight and ploidy, was characterized. Due to its small size, rapid growth, ease of characterization and maintenance, and distinct responses to different geminiviruses, “Florida Lanai” is an excellent choice for comparing geminivirus infection in a common host. DA - 2018/6// PY - 2018/6// DO - 10.1016/j.jviromet.2018.03.002 VL - 256 SP - 89-99 SN - 1879-0984 KW - Florida lanai KW - Tomato KW - Geminiviruses KW - Symptoms KW - qPCR KW - Ploidy KW - Seed transmission ER - TY - JOUR TI - In silico predicted glucose-1-phosphate Uridylyltransferase (GalU) inhibitors block a key pathway required for Listeria virulence AU - Kuenemann, M. A. AU - Spears, P. A. AU - Orndorff, P. E. AU - Fourches, D. T2 - Molecular Informatics DA - 2018/// PY - 2018/// VL - 37 IS - 6-7 ER - TY - JOUR TI - Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis AU - Wang, Jack P. AU - Matthews, Megan L. AU - Williams, Cranos M. AU - Shi, Rui AU - Yang, Chenmin AU - Tunlaya-Anukit, Sermsawat AU - Chen, Hsi-Chuan AU - Li, Quanzi AU - Liu, Jie AU - Lin, Chien-Yuan AU - Naik, Punith AU - Sun, Ying-Hsuan AU - Loziuk, Philip L. AU - Yeh, Ting-Feng AU - Kim, Hoon AU - Gjersing, Erica AU - Shollenberger, Todd AU - Shuford, Christopher M. AU - Song, Jina AU - Miller, Zachary AU - Huang, Yung-Yun AU - Edmunds, Charles W. AU - Liu, Baoguang AU - Sun, Yi AU - Lin, Ying-Chung Jimmy AU - Li, Wei AU - Chen, Hao AU - Peszlen, Ilona AU - Ducoste, Joel J. AU - Ralph, John AU - Chang, Hou-Min AU - Muddiman, David C. AU - Davis, Mark F. AU - Smith, Chris AU - Isik, Fikret AU - Sederoff, Ronald AU - Chiang, Vincent L. T2 - NATURE COMMUNICATIONS AB - A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation. DA - 2018/4/20/ PY - 2018/4/20/ DO - 10.1038/s41467-018-03863-z VL - 9 SP - SN - 2041-1723 ER - TY - JOUR TI - Improvement of Bartonella henselae DNA Detection in Cat Blood Samples by Combining Molecular and Culture Methods AU - Drummond, Marina Rovani AU - Lania, Bruno Grosselli AU - Diniz, Pedro Paulo Vissotto de Paiva AU - Gilioli, Rovilson AU - Demolin, Daniele Masselli Rodrigues AU - Scorpio, Diana Gerardi AU - Breitschwerdt, Edward B. AU - Velho, Paulo Eduardo Neves Ferreira T2 - Journal of Clinical Microbiology AB - ABSTRACT Bartonella spp. are bacteria of worldwide distribution that cause asymptomatic to fatal infections in animals and humans. The most common zoonotic species is Bartonella henselae , for which cats are the major natural reservoir host. To better understand Bartonella sp. diagnostic limitations, we determined the frequency of bloodstream infection in 112 cats by comparing and combining the results of multiple conventional and nested PCRs from blood and liquid culture samples. Using liquid culture conventional PCR, Bartonella sp. DNA was amplified from 27.7% of samples (31/112) compared to 90.2% of samples (101/112) by combining nested PCR from blood and liquid culture, indicating that PCR testing of more than one type of sample provides better sensitivity than a standalone PCR and that bloodstream infection is very frequent among cats in southeastern Brazil. This study reinforces the need for multistep testing for Bartonella sp. infection to prevent false-negative diagnostic results, even in reservoir hosts such as cats that typically maintain higher bacteremia levels. DA - 2018/3/14/ PY - 2018/3/14/ DO - 10.1128/jcm.01732-17 VL - 56 IS - 5 SP - J2 - J Clin Microbiol LA - en OP - SN - 0095-1137 1098-660X UR - http://dx.doi.org/10.1128/JCM.01732-17 DB - Crossref KW - bacteremia KW - Bartonella KW - cats KW - diagnosis KW - PCR ER - TY - JOUR TI - Genetic Variation for Resistance to Phytophthora Root Rot in Eastern White Pine Seedlings AU - Frampton, John AU - Pettersson, Martin AU - Braham, Anne Margaret T2 - FORESTS AB - Deployment of genetically resistant Eastern white pine (Pinus strobus L.) planting stock could reduce economic losses to root rot caused by Phytophthora cinnamomi Rands in Christmas tree and forest plantations. This study aimed to determine the degree of genetic control of resistance to P. cinnamomi in Eastern white pine and secondarily, to compare the aggressiveness of two P. cinnamomi isolates derived from different host species. Phytophthora isolates from Fraser fir (Abies fraseri (Pursh) Poir.) and Eastern white pine were used in a main and supplemental study, respectively, including 83 and 20 open-pollinated families. In each study, two-year-old seedlings were inoculated twice each of two consecutive years and mortality was assessed biweekly for 16 weeks each year. During the first year, mortality increased over time to 18.6% and 40.4% while family variation in mortality ranged from 1.3% to 60.0% and 12.5% to 73.0% in the main and supplemental studies, respectively. At the end of the first year, individual-tree and family-mean heritability estimates were, respectively, 0.44 ± 0.0935 and 0.85 ± 0.180 for the main study, and 0.57 ± 0.216 and 0.90 ± 0.343 for the supplemental study. The P. cinnamomi isolate from Eastern white pine was more aggressive and there was a large interaction between isolates and pine families. Deploying resistant families will be complicated by this interaction but should, nevertheless, reduce economic losses. DA - 2018/4// PY - 2018/4// DO - 10.3390/f9040161 VL - 9 IS - 4 SP - SN - 1999-4907 KW - Pinus strobus L. KW - Phytophthora cinnamomi Rands KW - disease resistance KW - family variation KW - Christmas trees KW - forest genetics ER - TY - JOUR TI - Synthesis of arrays containing porphyrin, chlorin, and perylene-imide constituents for panchromatic light-harvesting and charge separation AU - Hu, Gongfang AU - Kang, Hyun Suk AU - Mandal, Amit Kumar AU - Roy, Arpita AU - Kirmaier, Christine AU - Bocian, David F. AU - Holten, Dewey AU - Lindsey, Jonathan S. T2 - RSC ADVANCES AB - Achieving solar light harvesting followed by efficient charge separation and transport is an essential objective of molecular-based artificial photosynthesis. Architectures that afford strong absorption across the near-UV to near-infrared region, namely panchromatic absorptivity, are critically important given the broad spectral distribution of sunlight. A tetrapyrrole-perylene pentad array was synthesized and investigated as a means to integrate panchromatic light harvesting and intramolecular charge separation. The pentad consists of three moieties: (1) a panchromatically absorbing triad, in which a porphyrin is strongly coupled to two perylene-monoimides via ethyne linkages; (2) a perylene-diimide electron acceptor; and (3) a chlorin hole-trapping unit. Integrating the three components with diphenylethyne linkers generates moderate electronic coupling for intramolecular energy and hole/electron transfer. The construction of the array relies on a stepwise strategy for incorporating modular pigment building blocks. The key building blocks include a trans-A2BC porphyrin, a chlorin, a perylene-monoimide, and a perylene-diimide, each bearing appropriate (halo, ethynyl) synthetic handles for Pd-catalyzed Sonogashira coupling reactions. One target pentad, three tetrads, four triads, and four monomeric benchmark compounds were synthesized from six building blocks (three new, three reported) and 10 new synthetic intermediates. Four of the tetrapyrrole-containing arrays are zinc chelated, and four others are in the free base form. Absorption and fluorescence spectra and fluorescence quantum yields were also measured. Collectively, investigations of the arrays reveal insights into principles for the design of novel reaction centers integrated with a panchromatic antenna for artificial photosynthetic studies. DA - 2018/// PY - 2018/// DO - 10.1039/c8ra04052d VL - 8 IS - 42 SP - 23854-23874 SN - 2046-2069 ER - TY - JOUR TI - Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias AU - Mozayeni, Bobak Robert AU - Maggi, Ricardo Guillermo AU - Bradley, Julie Meredith AU - Breitschwerdt, Edward Bealmear T2 - Medicine AB - Introduction: Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp. Case report: This case report describes infections with Bartonella koehlerae and Bartonella henselae in a female veterinarian whose symptoms were predominantly rheumatologic in nature. Infection was confirmed by serology, polymerase chain reaction (PCR), enrichment blood culture, and DNA sequencing of amplified B koehlerae and B henselae DNA. Long-term medical management with antibiotics was required to achieve elimination of these infections and was accompanied by resolution of the patient's symptoms. Interestingly, the patient experienced substantial improvement in the acquired joint hypermobility mimicking Ehlers–Danlos Syndrome (EDS) type III. Conclusion: To facilitate early and directed medical interventions, systemic bartonellosis should potentially be considered as a differential diagnosis in patients with incalcitrant rheumatological symptoms and frequent arthropod exposures or extensive animal contact. DA - 2018/4// PY - 2018/4// DO - 10.1097/md.0000000000010465 VL - 97 IS - 17 SP - e0465 J2 - Medicine LA - en OP - SN - 0025-7974 UR - http://dx.doi.org/10.1097/MD.0000000000010465 DB - Crossref KW - Bartonella henselae KW - Bartonella koehlerae KW - bartonellosis KW - breast cyst KW - EDS Ehlers-Danlos KW - joint laxity KW - serology ER - TY - JOUR TI - Fusiform Rust Hazard Mapping for Loblolly Pine in the Southeastern United States Using Progeny Test Data AU - Walker, Trevor D. AU - McKeand, Steven E. T2 - JOURNAL OF FORESTRY DA - 2018/3// PY - 2018/3// DO - 10.5849/jof-2017-070 VL - 116 IS - 2 SP - 117-122 SN - 1938-3746 KW - fusiform rust KW - loblolly pine KW - hazard map KW - progeny test KW - genetic gain ER - TY - JOUR TI - Doxycycline treatment efficacy in dogs with naturally occurring Anaplasma phagocytophilum infection AU - Yancey, C. B. AU - Diniz, P. P. V. P. AU - Breitschwerdt, E. B. AU - Hegarty, B. C. AU - Wiesen, C. AU - Qurollo, B. A. T2 - JOURNAL OF SMALL ANIMAL PRACTICE AB - Objectives To evaluate doxycycline treatment efficacy and post‐treatment pathogen persistence in dogs naturally infected with Anaplasma phagocytophilum in endemic regions of the USA. Materials and Methods Symptomatic dogs in four US states (MN, WI, CT and CA) were evaluated before treatment with doxycycline and approximately 30 and 60 days post‐treatment. Clinicopathological parameters, co‐exposures and A. phagocytophilum DNA in whole blood and lymph node samples were compared between A. phagocytophilum infected and uninfected dogs. Results In total, 42 dogs fulfilled the inclusion criteria, with 16 dogs (38%) blood PCR‐positive and 26 dogs (62%) blood PCR‐negative for A. phagocytophilum . At initial evaluation, the proportion of clinicopathological abnormalities was similar between A. phagocytophilum infected and uninfected dogs, although thrombocytopenia and lymphopenia were statistically more prevalent among A. phagocytophilum infected dogs. Treatment with doxycycline resulted in resolution of all clinical abnormalities in infected dogs; four dogs had persistent haematological abnormalities, including mild leukopenia, eosinopenia and lymphopenia. All 16 infected dogs became blood PCR‐negative approximately 30 and 60 days after treatment onset. Additionally, 13/13 (100%) lymph node specimens tested post‐treatment were PCR‐negative. Select clinicopathological abnormalities persisted in uninfected dogs after treatment. Clinical Significance The results of this study support the efficacy of doxycycline therapy for clinical treatment of dogs naturally infected with A. phagocytophilum in the USA. This study did not find clinical, haematological or microbiological indicators that supported the persistence of A. phagocytophilum infection in naturally infected dogs following treatment with doxycycline for 28 days. DA - 2018/5// PY - 2018/5// DO - 10.1111/jsap.12799 VL - 59 IS - 5 SP - 286-293 SN - 1748-5827 ER - TY - JOUR TI - PhotochemCAD 3: Diverse Modules for Photophysical Calculations with Multiple Spectral Databases AU - Taniguchi, Masahiko AU - Du, Hai AU - Lindsey, Jonathan S. T2 - PHOTOCHEMISTRY AND PHOTOBIOLOGY AB - Abstract The Photochem CAD program, developed over 30 years, is described comprehensively with focus on features of the most recent version (Photochem CAD 3). The program is equipped with a streamlined user interface and provisions for handling multiple spectral databases. Eight modules enable calculations to be performed on the basis of the spectra in the databases. The calculational modules provide results concerning properties of individual compounds (oscillator strength, transition dipole moment, natural radiative lifetime), interactions of multiple compounds (Förster energy transfer, Dexter energy transfer, analysis of energy transfer among an array of chromophores) and composition of mixtures (multicomponent analysis). Synthetic spectra (blackbody radiator, Gaussian and Lorentzian curves, delta functions) also can be generated. For comparison and calculation, synthetic and experimental spectra can be shifted along both coordinate axes and combined by addition, subtraction and use of multiplicative factors. The core databases (described in the companion paper) have been expanded to 339 compounds for which absorption spectra (including molar absorption coefficient, ε ), fluorescence spectra (including fluorescence quantum yield, Φ f ) and references to the primary literature have been included where available (552 spectra altogether). A database of 31 solar spectra also is included. Each calculational module is described along with illustrative examples. DA - 2018/// PY - 2018/// DO - 10.1111/php.12862 VL - 94 IS - 2 SP - 277-289 SN - 1751-1097 ER - TY - JOUR TI - Identification of Hemotropic Mycoplasmas in an Eastern Box Turtle (Terrapene carolina carolina) and a Yellow-bellied Slider (Trachemys scripta scripta) from North Carolina, USA AU - Jarred, Jo AU - Lewbart, Gregory A. AU - Stover, Kelsey AU - Thomas, Brittany AU - Maggi, Ricardo AU - Breitschwerdt, Edward B. T2 - Journal of Wildlife Diseases AB - Mycoplasma spp. are known from several chelonian and other reptilian species. We determined if turtles obtained by the Turtle Rescue Team at North Carolina State University are carriers of hemotropic Mycoplasma or Bartonella spp. Spleen samples were collected at necropsy during May through July, 2014 from 53 turtles of seven species. All turtles were dead or were euthanized upon arrival due to severe traumatic injuries, or they died shortly after beginning treatment. We used PCR amplification for both bacterial genera; Bartonella spp. DNA was not amplified. Based upon sequencing of the 16S rRNA subunit, one eastern box turtle ( Terrapene carolina carolina) and one yellow-bellied slider ( Trachemys scripta scripta) were infected with Mycoplasma spp. that have genetic similarities to strains that infect other animals. DA - 2018/4// PY - 2018/4// DO - 10.7589/2017-07-153 VL - 54 IS - 2 SP - 371-374 J2 - Journal of Wildlife Diseases LA - en OP - SN - 0090-3558 UR - http://dx.doi.org/10.7589/2017-07-153 DB - Crossref KW - Chelonian KW - hemoplasma KW - hemotropic mycoplasma KW - PCR KW - wildlife ER - TY - JOUR TI - Genome-Wide Analysis of the Arabidopsis Replication Timing Program AU - Concia, Lorenzo AU - Brooks, Ashley M. AU - Wheeler, Emily AU - Zynda, Gregory J. AU - Wear, Emily E. AU - LeBlanc, Chantal AU - Song, Jawon AU - Lee, Tae-Jin AU - Pascuzzi, Pete E. AU - Martienssen, Robert A. AU - Vaughn, Matthew W. AU - Thompson, William F. AU - Hanley-Bowdoin, Linda T2 - PLANT PHYSIOLOGY AB - Eukaryotes use a temporally regulated process, known as the replication timing program, to ensure that their genomes are fully and accurately duplicated during S phase. Replication timing programs are predictive of genomic features and activity and are considered to be functional readouts of chromatin organization. Although replication timing programs have been described for yeast and animal systems, much less is known about the temporal regulation of plant DNA replication or its relationship to genome sequence and chromatin structure. We used the thymidine analog, 5-ethynyl-2′-deoxyuridine, in combination with flow sorting and Repli-Seq to describe, at high-resolution, the genome-wide replication timing program for Arabidopsis (Arabidopsis thaliana) Col-0 suspension cells. We identified genomic regions that replicate predominantly during early, mid, and late S phase, and correlated these regions with genomic features and with data for chromatin state, accessibility, and long-distance interaction. Arabidopsis chromosome arms tend to replicate early while pericentromeric regions replicate late. Early and mid-replicating regions are gene-rich and predominantly euchromatic, while late regions are rich in transposable elements and primarily heterochromatic. However, the distribution of chromatin states across the different times is complex, with each replication time corresponding to a mixture of states. Early and mid-replicating sequences interact with each other and not with late sequences, but early regions are more accessible than mid regions. The replication timing program in Arabidopsis reflects a bipartite genomic organization with early/mid-replicating regions and late regions forming separate, noninteracting compartments. The temporal order of DNA replication within the early/mid compartment may be modulated largely by chromatin accessibility. DA - 2018/3// PY - 2018/3// DO - 10.1104/pp.17.01537 VL - 176 IS - 3 SP - 2166-2185 SN - 1532-2548 UR - http://europepmc.org/abstract/med/29301956 ER - TY - JOUR TI - Database of Absorption and Fluorescence Spectra of > 300 Common Compounds for use in PhotochemCAD AU - Taniguchi, Masahiko AU - Lindsey, Jonathan S. T2 - PHOTOCHEMISTRY AND PHOTOBIOLOGY AB - The design of new molecules for photochemical studies typically requires knowledge of spectral features of pertinent chromophores beginning with the absorption spectrum (λabs ) and accompanying molar absorption coefficient (ε, m-1 cm-1 ) and often extending to the fluorescence spectrum (λem ) and fluorescence quantum yield (Φf ), where the fluorescence properties may be of direct relevance or useful as proxies to gain insight into the nature of the first excited singlet state. PhotochemCAD databases, developed over a period of 30 years, are described here. The previous databases for 150 compounds have been expanded to encompass 339 compounds for which absorption spectra (including ε values), fluorescence spectra (including Φf values) and references to the primary literature have been included where available (552 spectra altogether). The compounds exhibit spectra in the ultraviolet, visible and/or near-infrared spectral regions. The compound classes and number of members include acridines (21), aromatic hydrocarbons (41), arylmethane dyes (11), azo dyes (18), biomolecules (18), chlorins/bacteriochlorins (16), coumarins (14), cyanine dyes (19), dipyrrins (7), heterocycles (26), miscellaneous dyes (13), oligophenylenes (13), oligopyrroles (6), perylenes (5), phthalocyanines (11), polycyclic aromatic hydrocarbons (16), polyenes/polyynes (10), porphyrins (34), quinones (24) and xanthenes (15). A database of 31 solar spectra also is included. DA - 2018/// PY - 2018/// DO - 10.1111/php.12860 VL - 94 IS - 2 SP - 290-327 SN - 1751-1097 ER - TY - PCOMM TI - Potentially Same Novel Ehrlichia Species in Horses in Nicaragua and Brazil AU - Vieira, Thallitha S. W. J. AU - Qurollo, Barbara A. AU - Mongruel, Anna C. B. AU - Baggio, Rafael A. AU - Vidotto, Odilon AU - Breitschwerdt, Edward B. AU - Vieira, Rafael F. C. DA - 2018/5// PY - 2018/5// DO - 10.3201/eid2405.172076 SP - 953-953 ER - TY - JOUR TI - Population structure and migration of the Tobacco Blue Mold Pathogen,Peronospora tabacina,into North America and Europe AU - Blanco-Meneses, Monica AU - Carbone, Ignazio AU - Ristaino, Jean B. T2 - Molecular Ecology AB - Abstract Tobacco blue mold, caused by Peronospora tabacina , is an oomycete plant pathogen that causes yearly epidemics in tobacco ( Nicotiana tabacum ) in the United States and Europe. The genetic structure of P. tabacina was examined to understand genetic diversity, population structure and patterns of migration. Two nuclear loci, Igs2 and Ypt1, and one mitochondrial locus, cox 2, were amplified, cloned and sequenced from fifty‐four isolates of P. tabacina from the United States, Central America–Caribbean–Mexico ( CCAM ), Europe and the Middle East ( EULE ). Cloned sequences from the three genes showed high genetic variability across all populations. Nucleotide diversity and the population mean mutation parameter per site (Watterson's theta) were higher in EULE and CCAM and lower in U.S. populations. Neutrality tests were significant and the equilibrium model of neutral evolution was rejected, indicating an excess of recent mutations or rare alleles. Hudson's S nn tests were performed to examine population subdivision and gene flow among populations. An isolation‐with‐migration analysis ( IM ) supported the hypothesis of long‐distance migration of P. tabacina from the Caribbean region, Florida and Texas into other states in the United States. Within the European populations, the model documented migration from North Central Europe into western Europe and Lebanon, and migration from western Europe into Lebanon. The migration patterns observed support historical observations about the first disease introductions and movement in Europe. The models developed are applicable to other aerial dispersed emerging pathogens and document that high‐evolutionary‐risk plant pathogens can move over long distances to cause disease due to their large effective population size, population expansion and dispersal. DA - 2018/1/26/ PY - 2018/1/26/ DO - 10.1111/mec.14453 VL - 27 IS - 3 SP - 737-751 J2 - Mol Ecol LA - en OP - SN - 0962-1083 UR - http://dx.doi.org/10.1111/mec.14453 DB - Crossref KW - genetic structure KW - Peronospora tabacina KW - population genetics KW - tobacco ER - TY - JOUR TI - Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration AU - Meurs, K. M. AU - Friedenberg, S. G. AU - Williams, B. AU - Keene, B. W. AU - Atkins, C. E. AU - Adin, D. AU - Aona, B. AU - DeFrancesco, T. AU - Tou, S. AU - Mackay, T. T2 - VETERINARY JOURNAL AB - Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here. DA - 2018/2// PY - 2018/2// DO - 10.1016/j.tvjl.2017.12.002 VL - 232 SP - 16-19 SN - 1532-2971 KW - Canine KW - Cavalier King Charles spaniel KW - Dachshund KW - Genetic KW - Mitral valve KW - Myxomatous valve ER - TY - JOUR TI - Bartonella henselae in small Indian mongooses (Herpestes auropunctatus) from Grenada, West Indies AU - Jaffe, David A. AU - Chomel, Bruno B. AU - Kasten, Rickie W. AU - Breitschwerdt, Edward B. AU - Maggi, Ricardo G. AU - McLeish, Ashleigh AU - Zieger, Ulrike T2 - VETERINARY MICROBIOLOGY AB - Many mammals are established hosts for the vector borne bacterial genus, Bartonella. Small Indian mongooses (Herpestes auropunctatus) have only been reported as a possible host for Bartonella henselae in southern Japan. Confirming Bartonella presence in mongooses from other regions in the world may support their role as potential reservoirs of this human pathogen. Specifically, documenting Bartonella in Caribbean mongooses would identify a potential source of zoonotic risk with mongoose-human contact in the New World. Using serological and molecular techniques, we investigated B. henselae DNA and specific antibody prevalence in 171 mongooses from all six parishes in Grenada, West Indies. Almost a third (32.3%, 54/167) of the tested mongooses were B. henselae seropositive and extracted DNA from 18/51 (35.3%) blood pellets were PCR positive for the citrate synthase (gltA) and/or the β subunit of RNA polymerase (rpoB) genes. All sequences were identical to B. henselae genotype I, as previously reported from Japan. This study confirms the role of small Indian mongooses as a natural reservoir of B. henselae in the New World. DA - 2018/3// PY - 2018/3// DO - 10.1016/j.vetmic.2018.02.009 VL - 216 SP - 119-122 SN - 1873-2542 KW - Bartonella henselae KW - Herpestes auropunctatus KW - Small Indian mongoose KW - Grenada Island ER - TY - JOUR TI - Bartonella henselae infection in a dog with recalcitrant ineffective erythropoiesis AU - Randell, Martin G. AU - Balakrishnan, Nandhakumar AU - Gunn-Christie, Rebekah AU - Mackin, Andrew AU - Breitschwerdt, Edward B. T2 - Veterinary Clinical Pathology AB - Abstract Ineffective erythropoiesis was diagnosed in an 8‐year‐old male castrated Labrador Retriever. Despite treatment with immunosuppressive therapy for suspected immune‐mediated erythrocyte maturation arrest, resolution of the nonregenerative anemia was not achieved. Following documentation of Bartonella henselae bacteremia by Bartonella alpha proteobacteria growth medium ( BAPGM ) enrichment blood culture, immunosuppressive therapy was discontinued, and the anemia resolved following prolonged antibiotic therapy. Bartonella immunofluorescent antibody testing was negative, whereas B henselae western blot was consistently positive. The contribution of B henselae bacteremia to ineffective erythropoiesis remains unknown; however, the potential role of B henselae in the pathophysiology of bone marrow dyscrasias warrants additional investigation. DA - 2018/2/2/ PY - 2018/2/2/ DO - 10.1111/vcp.12575 VL - 47 IS - 1 SP - 45-50 J2 - Vet Clin Pathol LA - en OP - SN - 0275-6382 UR - http://dx.doi.org/10.1111/vcp.12575 DB - Crossref KW - Bartonella henselae KW - bone marrow dyscrasia KW - immunosuppression KW - ineffective erythropoiesis ER - TY - JOUR TI - Large sub-clonal variation in Phytophthora infestans from recent severe late blight epidemics in India AU - Dey, Tanmoy AU - Saville, Amanda AU - Myers, Kevin AU - Tewari, Susanta AU - Cooke, David E. L. AU - Tripathy, Sucheta AU - Fry, William E. AU - Ristaino, Jean B. AU - Guha Roy, Sanjoy T2 - Scientific Reports AB - The population structure of the Phytophthora infestans populations that caused the recent 2013-14 late blight epidemic in eastern India (EI) and northeastern India (NEI) was examined. The data provide new baseline information for populations of P. infestans in India. A migrant European 13_A2 genotype was responsible for the 2013-14 epidemic, replacing the existing populations. Mutations have generated substantial sub-clonal variation with 24 multi-locus genotypes (MLGs) found, of which 19 were unique variants not yet reported elsewhere globally. Samples from West Bengal were the most diverse and grouped alongside MLGs found in Europe, the UK and from neighbouring Bangladesh but were not linked directly to most samples from south India. The pathogen population was broadly more aggressive on potato than on tomato and resistant to the fungicide metalaxyl. Pathogen population diversity was higher in regions around the international borders with Bangladesh and Nepal. Overall, the multiple shared MLGs suggested genetic contributions from UK and Europe in addition to a sub-structure based on the geographical location within India. Our data indicate the need for improved phytosanitary procedures and continuous surveillance to prevent the further introduction of aggressive lineages of P. infestans into the country. DA - 2018/3/13/ PY - 2018/3/13/ DO - 10.1038/s41598-018-22192-1 VL - 8 IS - 1 SP - J2 - Sci Rep LA - en OP - SN - 2045-2322 UR - http://dx.doi.org/10.1038/s41598-018-22192-1 DB - Crossref ER - TY - JOUR TI - Expanding Covalent Attachment Sites of Nonnative Chromophores to Encompass the C-Terminal Hydrophilic Domain in Biohybrid Light-Harvesting Architectures AU - Hood, Don AU - Sahin, Tuba AU - Parkes-Loach, Pamela S. AU - Jiao, Jieying AU - Harris, Michelle A. AU - Dilbeck, Preston AU - Niedzwiedzki, Dariusz M. AU - Kirmaier, Christine AU - Loach, Paul A. AU - Bocian, David F. AU - Lindsey, Jonathan S. AU - Holten, Dewey T2 - CHEMPHOTOCHEM AB - Abstract Increasing the solar spectral coverage of native photosynthetic antennas can be achieved using biohybrid light‐harvesting (LH) structures comprised of native‐like bacterial photosynthetic peptides and synthetic bacteriochlorins with strong near‐infrared absorption. Four such biohybrids have been prepared wherein synthetic maleimido‐bearing bacteriochlorin BC1‐mal is covalently attached to a Cys residue substituted at either the +1, +5 or +11 position (relative to His‐0) of the 48‐residue β‐peptide of Rb. sphaeroides LH1. In addition, a β‐peptide with Phe substituted for Tyr at the +4 position along with +1Cys was used to examine possible quenching of the excited BC1 by the Tyr. The β‐peptide analogs, as well as their peptide‐ BC1 conjugates when combined with native α‐peptide, and bacteriochlorophyll a ( BChl a ) self‐assemble to form αβ‐dyads and therefrom LH1‐type cyclic (αβ) n oligomers. Static and time‐resolved optical studies show that all of the oligomeric assemblies transfer excitation energy from the appended BC1 to the BChl a array ( B875 ) with an average efficiency of 85 %. DA - 2018/3// PY - 2018/3// DO - 10.1002/cptc.201700182 VL - 2 IS - 3 SP - 300-313 SN - 2367-0932 KW - bacteriochlorin KW - bacteriochlorophyll KW - energy transfer KW - photosynthetic antennae KW - self-assembly ER - TY - JOUR TI - Chlorophyll-inspired red-region fluorophores: Building block synthesis and studies in aqueous media AU - Liu, R. AU - Liu, M. R. AU - Hood, D. AU - Chen, C. Y. AU - MacNevin, C. J. AU - Holten, D. AU - Lindsey, J. S. T2 - Molecules DA - 2018/// PY - 2018/// VL - 23 IS - 1 ER - TY - JOUR TI - Assessing the impact of the 4CL enzyme complex on the robustness of monolignol biosynthesis using metabolic pathway analysis AU - Naik, Punith AU - Wang, Jack P. AU - Sederoff, Ronald AU - Chiang, Vincent AU - Williams, Cranos AU - Ducoste, Joel J. T2 - PLOS ONE AB - Lignin is a polymer present in the secondary cell walls of all vascular plants. It is a known barrier to pulping and the extraction of high-energy sugars from cellulosic biomass. The challenge faced with predicting outcomes of transgenic plants with reduced lignin is due in part to the presence of unique protein-protein interactions that influence the regulation and metabolic flux in the pathway. Yet, it is unclear why certain plants have evolved to create these protein complexes. In this study, we use mathematical models to investigate the role that the protein complex, formed specifically between Ptr4CL3 and Ptr4CL5 enzymes, have on the monolignol biosynthesis pathway. The role of this Ptr4CL3-Ptr4CL5 enzyme complex on the steady state flux distribution was quantified by performing Monte Carlo simulations. The effect of this complex on the robustness and the homeostatic properties of the pathway were identified by performing sensitivity and stability analyses, respectively. Results from these robustness and stability analyses suggest that the monolignol biosynthetic pathway is resilient to mild perturbations in the presence of the Ptr4CL3-Ptr4CL5 complex. Specifically, the presence of Ptr4CL3-Ptr4CL5 complex increased the stability of the pathway by 22%. The robustness in the pathway is maintained due to the presence of multiple enzyme isoforms as well as the presence of alternative pathways resulting from the presence of the Ptr4CL3-Ptr4CL5 complex. DA - 2018/3/6/ PY - 2018/3/6/ DO - 10.1371/journal.pone.0193896 VL - 13 IS - 3 SP - SN - 1932-6203 ER - TY - JOUR TI - Sensitivity and specificity levels of two rapid assays for antibodies to Anaplasma spp. in dogs AU - Liu, Jiayou AU - Eberts, Matthew AU - Bewsey, Hannah AU - Thomas P. O'Connor, AU - Chandrashekar, Ramaswamy AU - Breitschwerdt, Edward B. T2 - JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION AB - Canine anaplasmosis is a tick-borne disease of dogs that results following infection with Anaplasma phagocytophilum or Anaplasma platys. The SNAP 4Dx Plus test (IDEXX Laboratories) and the VetScan Canine Anaplasma Rapid test (Abaxis) are commercial in-house rapid tests for the detection of antibody to these 2 antigenically related Anaplasma species. We evaluated 2 tests using serum and whole blood samples obtained from reference laboratories and veterinary hospitals. Samples were obtained from regions of the country known to be habitats of the primary tick vectors. The A. phagocytophilum sample set comprised 236 dog sera from the northeastern and midwestern United States; the A. platys sample set comprised 179 sera from dogs living in the southwestern United States. An indirect immunofluorescent antibody (IFA) test and an A. platys species-specific ELISA were used as reference assays for the A. phagocytophilum and A. platys samples, respectively. The SNAP test demonstrated significantly higher sensitivity (84.7% for A. phagocytophilum and 83.1% for A. platys), compared to the VetScan test (39.0% for A. phagocytophilum and 57.6% for A. platys). The specificity of the SNAP test (95.8% for A. phagocytophilum and 99.2% for A. platys) was significantly greater than the VetScan test (85.6% for A. phagocytophilum and 82.5% for A. platys). In a separate clinic study, conducted within an A. phagocytophilum–endemic state (Minnesota) using 154 whole blood samples from client-owned dogs, the VetScan test was negative for 22 of 39 SNAP and IFA seropositive samples. DA - 2018/3// PY - 2018/3// DO - 10.1177/1040638717745932 VL - 30 IS - 2 SP - 290-293 SN - 1943-4936 KW - Anaplasma phagocytophilum KW - dogs KW - tick-borne diseases ER - TY - JOUR TI - Quantitation of Tolyporphins, Diverse Tetrapyrrole Secondary Metabolites with Chlorophyll-Like Absorption, from a Filamentous Cyanobacterium-Microbial Community AU - Zhang, Yunlong AU - Zhang, Ran AU - Hughes, Rebecca-Ayme AU - Dai, Jingqiu AU - Gurr, Joshua R. AU - Williams, Philip G. AU - Miller, Eric S. AU - Lindsey, Jonathan S. T2 - PHYTOCHEMICAL ANALYSIS AB - Abstract Introduction Tolyporphins are unusual tetrapyrrole macrocycles produced by a non‐axenic filamentous cyanobacterium (HT‐58‐2). Tolyporphins A–J, L, and M share a common dioxobacteriochlorin core, differ in peripheral substituents, and exhibit absorption spectra that overlap that of the dominant cyanobacterial pigment, chlorophyll a . Identification and accurate quantitation of the various tolyporphins in these chlorophyll‐rich samples presents challenges. Objective To develop methods for the quantitative determination of tolyporphins produced under various growth conditions relative to that of chlorophyll a . Methodology Chromatographic fractionation of large‐scale (440 L) cultures afforded isolated individual tolyporphins. Lipophilic extraction of small‐scale (25 mL) cultures, HPLC separation with an internal standard, and absorption detection enabled quantitation of tolyporphin A and chlorophyll a , and by inference the amounts of tolyporphins A–M. Absorption spectroscopy with multicomponent analysis of lipophilic extracts (2 mL cultures) afforded the ratio of all tolyporphins to chlorophyll a . The reported absorption spectral data for the various tolyporphins required re‐evaluation for quantitative purposes. Results and Discussion The amount of tolyporphin A after 50 days of illumination ranged from 0.13 nmol/mg dry cells (media containing nitrate) to 1.12 nmol/mg (without nitrate), with maximum 0.23 times that of chlorophyll a . Under soluble‐nitrogen deprivation after 35–50 days, tolyporphin A represents 1/3–1/2 of the total tolyporphins, and the total amount of tolyporphins is up to 1.8‐fold that of chlorophyll a . Conclusions The quantitative methods developed herein should facilitate investigation of the biosynthesis of tolyporphins (and other tetrapyrroles) as well as examination of other strains for production of tolyporphins. Copyright © 2017 John Wiley & Sons, Ltd. DA - 2018/// PY - 2018/// DO - 10.1002/pca.2735 VL - 29 IS - 2 SP - 205-216 SN - 1099-1565 KW - HPLC KW - mass spectrometry KW - absorption spectroscopy with multicomponent analysis KW - nitrogen deprivation KW - growth curve ER - TY - JOUR TI - Datamonkey 2.0: A Modern Web Application for Characterizing Selective and Other Evolutionary Processes AU - Weaver, Steven AU - Shank, Stephen D. AU - Spielman, Stephanie J. AU - Li, Michael AU - Muse, Spencer V. AU - Pond, Sergei L. Kosakovsky T2 - MOLECULAR BIOLOGY AND EVOLUTION AB - Inference of how evolutionary forces have shaped extant genetic diversity is a cornerstone of modern comparative sequence analysis. Advances in sequence generation and increased statistical sophistication of relevant methods now allow researchers to extract ever more evolutionary signal from the data, albeit at an increased computational cost. Here, we announce the release of Datamonkey 2.0, a completely re-engineered version of the Datamonkey web-server for analyzing evolutionary signatures in sequence data. For this endeavor, we leveraged recent developments in open-source libraries that facilitate interactive, robust, and scalable web application development. Datamonkey 2.0 provides a carefully curated collection of methods for interrogating coding-sequence alignments for imprints of natural selection, packaged as a responsive (i.e. can be viewed on tablet and mobile devices), fully interactive, and API-enabled web application. To complement Datamonkey 2.0, we additionally release HyPhy Vision, an accompanying JavaScript application for visualizing analysis results. HyPhy Vision can also be used separately from Datamonkey 2.0 to visualize locally executed HyPhy analyses. Together, Datamonkey 2.0 and HyPhy Vision showcase how scientific software development can benefit from general-purpose open-source frameworks. Datamonkey 2.0 is freely and publicly available at http://www.datamonkey.org, and the underlying codebase is available from https://github.com/veg/datamonkey-js. DA - 2018/3// PY - 2018/3// DO - 10.1093/molbev/msx335 VL - 35 IS - 3 SP - 773-777 SN - 1537-1719 KW - natural selection KW - statistical methods KW - web application KW - recombination KW - evolutionary inference ER - TY - JOUR TI - Bartonella Seroepidemiology in Dogs from North America, 2008-2014 AU - Lashnits, E. AU - Correa, M. AU - Hegarty, B. C. AU - Birkenheuer, A. AU - Breitschwerdt, E. B. T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE AB - Improved understanding of Bartonella species seroepidemiology in dogs may aid clinical decision making and enhance current understanding of naturally occurring arthropod vector transmission of this pathogen.To identify demographic groups in which Bartonella exposure may be more likely, describe spatiotemporal variations in Bartonella seroreactivity, and examine co-exposures to other canine vector-borne diseases (CVBD).A total of 15,451 serology specimens from dogs in North America were submitted to the North Carolina State University, College of Veterinary Medicine Vector Borne Disease Diagnostic Laboratory between January 1, 2008, and December 31, 2014.Bartonella henselae, Bartonella koehlerae, and Bartonella vinsonii subspecies berkhoffii indirect fluorescent antibody (IFA) serology results, as well as results from a commercial assay kit screening for Dirofilaria immitis antigen and Ehrlichia species, Anaplasma phagocytophilum, and Borrelia burgdorferi antibodies, and Ehrlichia canis, Babesia canis, Babesia gibsoni, and Rickettsia species IFA results were reviewed retrospectively.Overall, 3.26% of dogs were Bartonella spp. seroreactive; B. henselae (2.13%) and B. koehlerae (2.39%) were detected more frequently than B. vinsonii subsp. berkhoffii (1.42%, P < 0.0001). Intact males had higher seroreactivity (5.04%) than neutered males (2.87%, P < 0.0001) or intact or spayed females (3.22%, P = 0.0003). Mixed breed dogs had higher seroreactivity (4.45%) than purebred dogs (3.02%, P = 0.0002). There was no trend in seasonal seroreactivity; geographic patterns supported broad distribution of exposure, and co-exposure with other CVBD was common.Bartonella spp. exposure was documented throughout North America and at any time of year. Male intact dogs, mixed breed dogs, and dogs exposed to other CVBD have higher seroreactivity to multiple Bartonella species. DA - 2018/// PY - 2018/// DO - 10.1111/jvim.14890 VL - 32 IS - 1 SP - 222-231 SN - 1939-1676 UR - https://doi.org/10.1111/jvim.14890 KW - Canine KW - Seroreactivity KW - Zoonoses ER - TY - JOUR TI - Estimating Realized Heritability in Panmictic Populations AU - Lstiburek, Milan AU - Bittner, Vaclav AU - Hodge, Gary R. AU - Picek, Jan AU - Mackay, Trudy F. C. T2 - GENETICS AB - Abstract Narrow sense heritability (h2) is a key concept in quantitative genetics, as it expresses the proportion of the observed phenotypic variation that is transmissible from parents to offspring. h2 determines the resemblance among relatives, and the rate of response to artificial and natural selection. Classical methods for estimating h2 use random samples of individuals with known relatedness, as well as response to artificial selection, when it is called realized heritability. Here, we present a method for estimating realized h2 based on a simple assessment of a random-mating population with no artificial manipulation of the population structure, and derive SE of the estimates. This method can be applied to arbitrary phenotypic segments of the population (for example, the top-ranking p parents and offspring), rather than random samples. It can thus be applied to nonpedigreed random mating populations, where relatedness is determined from molecular markers in the p selected parents and offspring, thus substantially saving on genotyping costs. Further, we assessed the method by stochastic simulations, and, as expected from the mathematical derivation, it provides unbiased estimates of h2. We compared our approach to the regression and maximum-likelihood approaches utilizing Galton’s dataset on human heights, and all three methods provided identical results. DA - 2018/1// PY - 2018/1// DO - 10.1534/genetics.117.300508 VL - 208 IS - 1 SP - 89-95 SN - 1943-2631 KW - quantitative genetics KW - Hardy-Weinberg equilibrium KW - panmictic population ER -