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Sanger sequencing confirmed the stallion was heterozygous for the MITF deletion. No SNPs or structural variants were identified in PAX3 or any of the other candidate genes that were unique to the stallion or predicted to affect protein function. Genotyping five of the stallion's splashed white offspring, including one all white foal, found that they were also heterozygous for the deletion. Given the role of MITF in producing white pattern phenotypes, and the predicted deleterious effect of this mutation, this 8.7 kb deletion is the likely causal variant for SW6. © The American Genetic Association 2020.This report describes the phenotypic characteristics of a novel Penicillium species, Penicillium labradorum, isolated from a 3-year-old male, castrated, Labrador retriever with disseminated fungal disease. The dog's presenting clinical signs included lethargy, lymphadenopathy, tachypnea, moderate pitting edema, and nonweight bearing lameness associated with the right hind limb. Fine-needle aspirate biopsies from the sublumbar and prescapular lymph nodes were initially examined. The cytologic findings were consistent with pyogranulomatous inflammation with abundant extracellular and phagocytized fungal fragments and hyphae. Based on the morphology of the organisms and lack of endogenous pigment, hyalohyphomycosis was considered most likely, with Fusarium, Penicillium, and Paecilomyces species being considerations. Fungal isolates were obtained via culture of samples from the lymph nodes, and molecular identification testing originally identified an undescribed Penicillium species belonging to the Penicillium section Exilicaulis. BLAST searches and phylogenetic analyses performed approximately 1 year and 9 months after the isolation date revealed an isolate within the Penicillium parvum clade in the Penicillium section Exilicaulis but phylogenetically distant from the other species in the section, thus representing a new species, Penicillium labradorum. Antifungal susceptibility testing was also performed on the isolate and low minimum inhibitory concentrations were observed with terbinafine, voriconazole, and posaconazole, while in vitro resistance was observed with fluconazole. The dog had been previously treated with fluconazole, itraconazole, amphotericin B lipid complex, voriconazole, and terbinafine. Approximately 587 days after the initial diagnosis, the dog was euthanized due to worsening of clinical signs and concerns for quality of life. © The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.The genus Malassezia comprises a heterogeneous group of species that cause similar pathologies. Malassezia yeasts were considered as the most abundant skin eukaryotes of the total skin mycobiome. The ability of this fungus to colonize or infect is determined by complex interactions between the fungal cell and its virulence factors. This study aims to evaluate in vitro the hydrophobicity levels, the adherence capacity on a polystyrene surface and the ability to form biofilm of 19 isolates, including M. sympodialis, M. globosa, and M. slooffiae, from healthy subjects and from dermatological disorders. Cellular surface hydrophobicity levels were determined by two-phase system. The biofilm formation was determined by tetrazolium salt (XTT) reduction assay and by Scanning Electron Microscopy (SEM). Strain dependence was observed in all virulence factors studied. All isolates of M. sympodialis, M. globosa, and M. slooffiae demonstrated their ability to form biofilm at variable capacities. [https://www.selleckchem.com/products/cepharanthine.html learn more] SEM observations confirmed a variable extracellular matrix after 48&nbsp;hours of biofilm formation. All isolates of M. globosa were highly adherent and/or hydrophobic as well as biofilm producers. In contrast, M. slooffiae was the least biofilm producer. No significant differences between virulence factors were demonstrated for M. sympodialis, either as clinical isolate or as inhabitant of human microbiota. Results of this work together with the previous M. furfur research confirm that the most frequently Malassezia species isolated from normal subject's skin and patients with dermatosis, form biofilm with different capacities. The study of these virulence factors is important to highlight differences between Malassezia species and to determine their involvement in pathological processes. © The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.Zika virus (ZIKV) was discovered over 70 years ago in East Africa but little is known about its circulation and pathogenesis there. We screened 327 plasma samples collected 2-12 months after febrile illness in Western and coastal Kenya (1993-2016) for binding and neutralizing antibodies to distinguish ZIKV and Dengue virus (DENV) responses, which we found were common in coastal Kenya. Two cases had durable ZIKV-specific antibodies and two cases had ZIKV antibodies at similar levels as DENV antibodies. This suggests low-level ZIKV circulation in Kenya over two decades and sets a baseline for future surveillance efforts in East Africa. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Obesity is a serious chronic disease whose prevalence has grown to epidemic proportions over the past five decades and is a major contributor to the global burden of most common cancers, heart disease, Type 2 diabetes, liver disease, and sleep apnea. Primary care clinicians, including physicians, nurse practitioners, and physician assistants, are often the first health care professionals to identify obesity or overweight during routine long-term care and have the opportunity to intervene to prevent and treat disease. However, they often lack the training and skills needed to deliver scientifically validated, behavior-based treatments. These gaps must be addressed in order to treat the obesity epidemic. The Society of Behavioral Medicine strongly urges health professional educators and accrediting agencies to include obesity and overweight management education for primary care clinicians. Additionally, we support promoting referrals and reimbursement for psychologists, dieticians, and other health care professionals as critical members of the care team and improving reimbursement levels for behavioral obesity and overweight management treatment. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.Nek7 is a serine/threonine protein kinase required for proper spindle formation and cytokinesis. Elevated Nek7 levels have been observed in several cancers, and inhibition of Nek7 might provide a route to the development of cancer therapeutics. To date no selective and potent Nek7 inhibitors have been identified. Nek7 crystal structures exhibit an improperly formed Regulatory-spine (R-spine), characteristic of an inactive kinase. We reasoned that the preference of Nek7 to crystallize in this inactive conformation might hinder attempts to capture Nek7 in complex with Type I inhibitors. Here we have introduced aromatic residues into the R-spine of Nek7 with the aim to stabilize the active conformation of the kinase through R-spine stacking. The strong R-spine mutant Nek7SRSretained catalytic activity and was crystallized in complex with compound 51, an ATP-competitive inhibitor of Nek2 and Nek7. Subsequently, we obtained the same crystal form for wild-type Nek7WTin apo form and bound to compound 51. The R-spines of the three well-ordered Nek7WTmolecules exhibit variable conformations while the R-spines of the Nek7SRSmolecules all have the same, partially stacked configuration. Compound 51 bound to Nek2 and Nek7 in similar modes, but differences in the precise orientation of a substituent highlights features that could be exploited in designing inhibitors that are selective for particular Nek family members. Although the SRS mutations are not required to obtain a Nek7-inhibitor structure, we conclude that it is a useful strategy for restraining the conformation of a kinase in order to promote crystallogenesis. Copyright 2020 The Author(s).Clostridioides difficileis a spore-forming bacterial pathogen that is the leading cause of hospital-acquired gastroenteritis. C. difficileinfections begin when its spore form germinates in the gut upon sensing bile acids. These germinants induce a proteolytic signaling cascade controlled by three members of the subtilisin-like serine protease family, CspA, CspB, and CspC. Notably, even though CspC and CspA are both pseudoproteases, they are nevertheless required to sense germinants and activate the protease, CspB. Thus, CspC and CspA are part of a growing list of pseudoenzymes that play important roles in regulating cellular processes. However, despite their importance, the structural properties of pseudoenzymes that allow them to function as regulators remain poorly understood. Our recently solved crystal structure of CspC revealed that its pseudoactive site residues align closely with the catalytic triad of CspB, suggesting that it might be possible to "resurrect" the ancestral protease activity of the CspC and CspA pseudoproteases. Here, we demonstrate that restoring the catalytic triad to these pseudoproteases fails to resurrect their protease activity. We further show that the pseudoactive site substitutions differentially affect the stability and function of the CspC and CspA pseudoproteases the substitutions destabilized CspC and impaired spore germination without affecting CspA stability or function. Thus, our results surprisingly reveal that the presence of a catalytic triad does not necessarily predict protease activity. Since homologs of C. difficile CspA occasionally carry an intact catalytic triad, our results indicate that bioinformatic predictions of enzyme activity may underestimate pseudoenzymes in rare cases. Copyright 2020 The Author(s).Cadmium is ovarian toxic in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle stimulating hormone concentrations (≥10 IU/L), in women ages 35-49 (unweighted n=1,681). Using data from the Third National Health and Nutrition Examination Survey, 1988-94, we conducted Poisson regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CI). Because the best approach to correct for urinary dilution in spot samples with creatinine remains controversial, we employed three approaches standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest vs. lowest quartile RR 1.3, 95% CI 0.8, 1.9; Ptrend=0.06) and covariate-adjusted standardization (highest vs. lowest quartile RR 1.3, 95% CI 0.9, 1.9; Ptrend=0.05), and a stronger association with covariate adjustment (highest vs. lowest quartile RR 1.8, 95% CI 1.2, 2.9; Ptrend=0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine-adjustment approach is needed to minimize bias. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020.