Isolated populations with novel phenotypes present an exciting opportunity to uncover the genetic basis of ecologically significant adaptation, and genomic scans have often, but not always, led to candidate genes directly related to an adaptive phenotype. However, in many cases these populations were established by a severe bottleneck, which can make identifying targets of selection problematic. Here, we simulate severe bottlenecks and subsequent selection on standing variation, mimicking adaptation after establishment of a new small...

Seed germination is a key life history transition for annual plants and partly determines lifetime performance and fitness. Germination speed, the elapsed time for a nondormant seed to germinate, is a poorly understood trait important for plants’ competitiveness and fitness in fluctuating environments. Germination speed varied by 30% among 18 Arabidopsis thaliana populations measured, and exhibited weak negative correlation with flowering time and seed weight, with significant genotype effect (P < 0.005). To dissect the...

Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified miR-126 as a target...

The San Andreas Fault (SAF) in California is a mature plate boundary fault capable of great (magnitude 8 or greater) earthquakes. The southern section of the SAF has not produced a major event in historic times (over the last 300 years), and is currently believed to pose the largest seismic risk in California (Weldon et al., 2005; Field et al., 2014). While much progress was made toward understanding seismic potential of the Southern San Andreas...

Objective: To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer’s disease (AD) using a community-dwelling cohort of women (aged 71-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). Methods: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas...

Settlement and metamorphosis mark a critical transition in the life cycle of marine invertebrates, during which substantial mortality occurs in both field and laboratory settings. Previous pair-crossing experiments with the Pacific oyster Crassostrea gigas have revealed significant selective or genotype-dependent mortality around the metamorphic transition, but the fine-scale nature and timing of this mortality is not known, particularly whether it occurs before, during or after metamorphosis. In this laboratory study, microsatellite marker segregation ratios were...

Domesticated species are impacted in unintended ways during domestication and breeding. Changes in the nature and intensity of selection impart genetic drift, reduce diversity, and increase the frequency of deleterious alleles. Such outcomes constrain our ability to expand the cultivation of crops into environments that differ from those under which domestication occurred. We address this need in chickpea, an important pulse legume, by harnessing the diversity of wild crop relatives. We document an extreme domestication-related...

Existing research demonstrates that financial constraints are widespread and influence consumer attention, preference, choice, and consumption in a variety of ways. Despite the growing knowledge of how financial constraints affect the consumer decision making process, less is known about its impact on post-purchase behavior. This work examines whether financial constraints impact an important post-purchase behavior—word-of-mouth—and in what direction. Seven studies show that financial constraints reduce purchase-related word-of-mouth. This effect emerges across consumers’ reported frequencies of...

Purpose: The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency status (dMMR), and programmed cell death-ligand 1 (PD-L1) expression. Herein, we attempt to quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Experimental Design: A total of 4125 tumors from 14 different gastrointestinal cancer sites were studied. Next-generation sequencing was performed on genomic...

LA-PTH is a long-acting parathyroid hormone (PTH) peptide analog in pre-clinical development for hypoparathyroidism (HP). Like native PTH, LA-PTH contains a methionine at position 8 that is predicted to be critical for function. We assessed the impact of methionine oxidation on the functional properties of LA-PTH and control PTH ligands. Oxidation of PTH(1-34) resulted in marked (~20-fold) reductions in binding affinity on the PTH receptor-1 (PTHR1) in cell membranes, similarly diminished potency for cAMP signaling...

Intraspecific trait variation within natural populations (i.e. intra‐population trait variation, IPTV) is the basic source for selection and can have significant ecological consequences. Higher IPTV may increase a population's niche breath and benefit interspecies competition under a resource‐limited environment, thus affecting the ability of a species to move into novel habitats. However, the reciprocal influences of variation in environmental conditions and phenotypic trait expression in spreading plant populations are not clearly defined. We propose that...

Background: Lung nodules are a diagnostic challenge, with an estimated yearly incidence of 1.6 million in the United States. This study evaluated the accuracy of an integrated proteomic classifier in identifying benign nodules in patients with a pretest probability of cancer (pCA) ≤ 50%. Methods: A prospective, multicenter observational trial of 685 patients with 8- to 30-mm lung nodules was conducted. Multiple reaction monitoring mass spectrometry was used to measure the relative abundance of two...

Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size...

Food insecurity has been associated with adverse effects on physical health and well-being in both high and low-income countries, but effects on brain health are not clear. The purpose of this systematic review was to determine the relationship between food insecurity and important brain health outcomes in adults including depression, stroke, cognitive impairment and dementia. Electronic databases were searched to find studies which investigated relations between food insecurity and predefined brain health outcomes. Thirty studies...

Exposure to metals increases risk for pregnancy complications. Extracellular vesicle (EV) miRNA contribute to maternal-foetal communication and are dysregulated in pregnancy complications. However, metal impacts on maternal circulating EV miRNA during pregnancy are unknown. Our objective was to investigate the impact of multiple metal exposures on EV miRNA in maternal circulation during pregnancy in the MADRES Study. Associations between urinary concentrations of nine metals and 106 EV miRNA in maternal plasma during pregnancy were investigated...

The Santa Rosa fossil locality in eastern Perú produced the first Paleogene vertebrate fauna from the Amazon Basin, including the oldest known monkeys from South America. This diverse paleofauna was originally assigned an Eocene age, based largely on the stage of evolution of the site’s caviomorph rodents and marsupials. Here we present new detrital zircon dates that indicate that the maximum composite age of Santa Rosa is 29.6±0.8 Ma (Lower Oligocene), although several zircons from...

Neogene and Pleistocene African suids displayed convergent evolutionary trends in the third molar (M3) morphology, with increasingly elongated and higher crowns through time. While these features can prevent premature loss of masticatory functionality and potentially increase long-term reproductive success, changes in dental occlusal traits such as enamel complexity and thickness can also improve chewing efficiency and increase short-term energetic return. While both long-term and short-term benefits can contribute to the thriving of a lineage, the...

We examine temporal and spatial variation in morphology of the ammonoid cephalopod Discoscaphites iris using a large dataset from multiple localities in the Late Cretaceous (Maastrichtian) of the United States Gulf and Atlantic Coastal Plains, spanning a distance of 2000 km along the paleoshoreline. Our results suggest that the fossil record of D. iris is consistent with no within species net accumulation of phyletic evolutionary change across morphological traits or the lifetime of this species....

This study aimed to explore the modulatory effects of menopause hormone therapy (MHT) on mood disorders among postmenopausal women. A cross-sectional study was conducted to recruit postmenopausal women, including patients (arranged MHT for over 3 years as the medication group) and non-MHT controls. All participants were asked to respond to the Center for Epidemiological Studies Depression Scale (CES-D) and Generalized Anxiety Disorder Screener (GAD-7) questionnaires to assess their depression and anxiety status. A total of...

Additional file 1. Table S1: Patient demography.

Additional file 4: Table S3. NRAS overexpression induces basal-like features in a human luminal DCIS model SUM225 cells.

Additional file 1: Table S1. Pathological, Biomarker and Demographic Characteristics of the patients in the TMAs.

Additional file 9: Table S2: Acetylated proteins and acetylated peptides identified in this study.

Additional file 1: Table S1. Clinical information of study cases. Table S2. Expression of proteins from the PDAC tumors and NATs

Candida albicans is an opportunistic human fungal pathogen that exists in normal flora but can cause infection in immunocompromised individuals. The transition to pathogenic C. albicans requires a change of various gene expressions. Because histone-modifying enzymes can regulate gene expression, they are thought to control the virulence of C. albicans. Indeed, the absence of H3 lysine 4 (H3K4) methyltransferase Set1 has been shown to reduce the virulence of C. albicans; however, Set1-regulated genes responsible for...