Blantonbergmann4123

We demonstrate our method on a small group of dendrobatid frogs and show that it can make inferences given species with restricted ranges and little occurrence data. We also use simulations to show that our method can reliably reconstruct the niche of a known ancestor in both geographic and environmental space. Our method brings together fields as disparate as ecological niche modeling, phylogenetics, and ancestral range estimation in a user-friendly package.Cichlid fishes exhibit rapid, extensive, and replicative adaptive radiation in feeding morphology. Plasticity of the cichlid jaw has also been well documented, and this combination of iterative evolution and developmental plasticity has led to the proposition that the cichlid feeding apparatus represents a morphological "flexible stem". Under this scenario, the fixation of environmentally sensitive genetic variation drives evolutionary divergence along a phenotypic axis established by the initial plastic response. Thus, if plasticity is predictable then so too should be the evolutionary response. We set out to explore these ideas at the molecular level by identifying genes that underlie both the evolution and plasticity of the cichlid jaw. As a first step, we fine-mapped an environment-specific QTL for lower jaw shape in cichlids, and identified a non-synonymous mutation in the ciliary rootlet coiled-coil 2 (crocc2), which encodes a major structural component of the primary cilium. Given that primary cilia play key roles in skeletal mechanosensing, we reasoned that this gene may confer its effects by regulating the sensitivity of bone to respond to mechanical input. Using both cichlids and zebrafish, we confirmed this prediction through a series of experiments targeting multiple levels of biological organization. Taken together, our results implicate crocc2 as a novel mediator of bone formation, plasticity and evolution.The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor in the Per-Arnt-Sim superfamily of environmental sensors that is linked to several metabolic diseases, including nonalcoholic fatty liver disease. Much remains unknown regarding the impact of genetic variation in AHR-driven disease, as past studies have focused on a small number of inbred strains. Recently, the presence of a wide range of interindividual variability amongst humans was reported in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical ligand of the AHR. In this study, a panel of 14 diverse mouse strains was exposed to TCDD for 10 days to characterize the AHR-mediated response across genetic backgrounds. Responses to TCDD are heavily dependent on genetic background. Although mice carry 1 of 4 Ahr alleles known to impact the affinity to AHR-ligands, we observed significant intra-allelic variability suggesting the presence of novel genetic modifiers of AHR signaling. A regression-based approach was used to scan for genes regulated by the AHR and/or associated with TCDD-induced phenotypes. The approach identified 7 genes, 2 of which are novel, that are likely regulated by the AHR based on association with hepatic TCDD burden (p ≤ .05). Finally, we identified 1 gene, Dio1, which was associated with change in percent body fat across the diverse set of strains (p ≤ .05). Overall, the results in this study exemplify the power of genetics-based approaches in identifying novel genes that are putatively regulated by the AHR.This review describes how Twitter is currently used by laboratory professionals for education, research, and networking. This platform has a global audience. It enables users to post information publicly, easily, rapidly, and free of charge. The absence of hierarchies enables interactions that may not be feasible offline. Laboratory professionals teach thousands of people using text, images, polls, and videos. Academic discussion flourishes without paywalls. Published research is shared faster than ever before, articles are discussed in online journal clubs, and research collaborations are facilitated. Pathologists network globally and make new friends within and beyond their specialty. Pathology departments and residency programs showcase trainees and faculty and celebrate graduations. As users in one time zone go to bed, others who are just waking up begin to read and tweet, creating a 24/7/365 live global online conference. DRB18 research buy We encourage others to plug into the power of Twitter, the network that never sleeps.

Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at ten or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail.

Frailty was measured at study entry and five years later. Logistic regression tested the associations of several factors with having frailty at five years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates.

Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were age 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0%-7.5%) to 13.6% (95% CI = 11.9%-15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation ≥20 Gy (odds ratio [OR] = 1.98, 95% CI = 1.29-3.05), cardiac (Ocluding lack of strength training and sedentary lifestyle may decrease risk of adverse health events and improve longevity in survivors.

Parabens are used as preservatives in consumer products but are suspected of having endocrine-disrupting properties. A recent study reported an association between in utero exposure to butyl paraben and overweight in childhood, with a stronger trend in girls.

We therefore studied the association between parabens in maternal urine in third trimester and fat percentage in children aged 7 years.

We used data from the Odense Child Cohort, a mother-child cohort with enrollment from 2010 to 2012, in which the children are followed. Paraben concentration was assessed in maternal urine at median gestational week 28.7 and body composition measured as total, gynoid, and android fat percentages assessed by dual X-ray absorptiometry in their children at age 7 years.

Total, gynoid, and android fat percentages and z-score for body mass index.

None.

Paraben exposure was low. In multivariate linear regressions, detection of butylparaben in maternal urine was associated with an increase of 17% [95% confidence intervals (CI) 3.0%, 32%] in total body fat percentage and an increase of 23% (95% CI 5.1%, 43%) in android fat percentage in boys, compared to boys whose mother had no detectable butylparaben in urine. No significant associations between in utero exposure to methyl-, ethyl- or propyl parabens and body composition were found, and no significant associations were seen in girls.

Our findings suggest that parabens, which are believed to have low toxicity, may affect obesity development at vulnerable time periods during development.

Our findings suggest that parabens, which are believed to have low toxicity, may affect obesity development at vulnerable time periods during development.Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.The Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline on Chronic Kidney Disease (1) recommends calculating estimated glomerular filtration rate (eGFR) using equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for adults ≥18 years (2) and by the Chronic Kidney Disease in Children (CKiD) for ages less then 18 years (3). These equations were recommended because they used readily available information, serum/plasma/blood creatinine, plus age, sex, and race for adults, and height for children; and have been validated in large and diverse cohorts of people who had measured glomerular filtration rate (mGFR) as a basis for establishing accuracy.Acute myeloid leukemia (AML) cells have an atypical metabolic phenotype characterized by increased mitochondrial mass, as well as a greater reliance on oxidative phosphorylation and fatty acid oxidation (FAO) for survival. To exploit this altered metabolism, we assessed publicly available databases to identify FAO enzyme overexpression. Very long chain acyl-CoA dehydrogenase (VLCAD; ACADVL) was found to be overexpressed and critical to leukemia cell mitochondrial metabolism. Genetic attenuation or pharmacological inhibition of VLCAD hindered mitochondrial respiration and FAO contribution to the tricarboxylic acid cycle, resulting in decreased viability, proliferation, clonogenic growth, and AML cell engraftment. Suppression of FAO at VLCAD triggered an increase in pyruvate dehydrogenase activity that was insufficient to increase glycolysis but resulted in adenosine triphosphate depletion and AML cell death, with no effect on normal hematopoietic cells. Together, these results demonstrate the importance of VLCAD in AML cell biology and highlight a novel metabolic vulnerability for this devastating disease.Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GVL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the Experimental Therapeutics Clinical Trials Network 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T-cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T-cell populations and increased expression of markers of T-cell activation and costimulation such as PD-1, HLA-DR, and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T-cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab.