bluuebunny/crossref_metadata_2025_split huggingface dataset:
How squirrels protect their caches: Location, conspicuousness during caching, and proximity to kin influence cache lifespan
Authors: Delgado Mikel M. , Jacobs Lucia F. 
Published: August 2019

AbstractScatter-hoarding animals cannot physically protect individual caches, and instead utilize several behavioral strategies that are hypothesized to offer protection for caches. We validated the use of physically altered, cacheable food items, and determined that intraspecific pilfering among free-ranging fox squirrels (N = 23) could be assessed in the field. In this study we were able to identify specific individual squirrels who pilfered or moved caches that had been stored by a conspecific. We identified a high level of pilfering (25%) among this population. In a subsequent study, we assessed the fate of squirrel-made caches. Nineteen fox squirrels cached 294 hazelnuts with passive integrated transponder tags implanted in them. Variables collected included assessment and cache investment and protection behaviors; cache location, substrate, and conspicuousness of each cache; how long each cache remained in its original location, and the location where the cache was finally consumed. We also examined whether assessment or cache protection behaviors were related to the outcomes of buried nuts. Finally, we measured the population dynamics and heterogeneity of squirrels in this study, testing the hypothesis that cache proximity and pilferage tolerance could serve as a form of kin selection. Polymer chain reaction (PCR) was used to analyze hair samples and determine relatedness among 15 squirrels, and the potential impact of relatedness on caching behavior. Results suggested that cache protection behaviors and the lifespan of a cache were dependent on the conspicuousness of a cache. Squirrels may mitigate some of the costs of pilfering by caching closer to the caches of related squirrels than to those of non-related squirrels.
Penetrance of Parkinson’s disease in LRRK2 p.G2019S carriers is modified by a polygenic risk score
Authors: Iwaki Hirotaka , Blauwendraat Cornelis , Makarious Mary B. , Bandrés-Ciga Sara , Leonard Hampton L. , Gibbs J. Raphael , Hernandez Dena G. , Scholz Sonia W. , Faghri Faraz ,   International Parkinson’s Disease Genomics Consortium (IPDGC), Nalls Mike A. , Singleton Andrew B. 
Published: August 2019

AbstractBackgroundWhile the LRRK2 p.G2019S mutation has been demonstrated to be a strong risk factor for Parkinson’s Disease (PD), factors that contribute to penetrance among carriers, other than aging, have not been well identified.ObjectivesTo evaluate whether a cumulative genetic risk identified in the recent genome-wide study is associated with penetrance of PD among p.G2019S mutation carriers.MethodsWe included p.G2019S heterozygote carriers with European ancestry in three genetic cohorts in which the mutation carriers with and without PD were selectively recruited. We also included the carriers from two datasets: one from a case-control setting without selection of mutation carriers, and the other from a population sampling. The associations between PRS constructed from 89 variants reported in Nalls et al. and PD were tested and meta-analyzed. We also explored the interaction of age and PRS.ResultsAfter excluding 8 homozygotes, 833 p.G2019S heterozygote carriers (439 PD and 394 unaffected) were analyzed. PRS was associated with a higher penetrance of PD (OR 1.34, 95% C.I. [1.09, 1.64] per +1 SD, P = 0.005). In addition, associations with PRS and penetrance were stronger in the younger participants (main effect: OR 1.28 [1.04, 1.58] per +1 SD, P = 0.022; interaction effect: OR 0.78 [0.64, 0.94] per +1 SD and +10 years of age, P = 0.008).ConclusionsOur results suggest that there is a genetic contribution for penetrance of PD among p.G2019S carriers. These results have important etiologic consequences and potential impact on the selection of subjects for clinical trials.
S. pombeDNA translocases Rrp1 and Rrp2 have distinct roles at centromeres and telomeres that ensure genome stability
Authors: Barg-Wojas Anna , Schirmeisen Kamila , Muraszko Jakub , Kramarz Karol , Baranowska Gabriela , Carr Antony M. , Dziadkowiec Dorota 
Published: August 2019

ABSTRACTHomologous recombination (HR) is a DNA repair mechanism that ensures, together with heterochromatin machinery, the proper replication, structure and function of telomeres and centromeres that is essential for the maintenance of genome integrity.Schizosaccharomyces pombeRrp1 and Rrp2 participate in HR and are orthologues ofSaccharomyces cerevisiaeUls1, a SWI2/SNF2 DNA translocase and SUMO-Targeted Ubiquitin Ligase. We show that Rrp1 or Rrp2 upregulation leads to chromosome instability and growth defects. These phenotypes depend on putative DNA translocase activities of Rrp1 and Rrp2. Either Rrp1 or Rrp2 overproduction results in a reduction in global histone levels, suggesting that Rrp1 and Rrp2 may modulate nucleosome dynamics. In addition we show that Rrp2, but not Rrp1, acts at telomeres. We propose that this role depends on the previously described interaction between Rrp2 and Top2. We conclude that Rrp1 and Rrp2 have important roles for centromere and telomere function and maintenance, contributing to the preservation of genome stability during vegetative cell growth.SUMMARY STATEMENTSchizosaccharomyces pombeDNA translocases Rrp1 and Rrp2 modulate centromere and telomere maintenance pathways and dysregulation of their activity leads to genome instability.
Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15
Authors: Faust Tyler , Yoon Hojong , Nowak Radosław P. , Donovan Katherine A. , Li Zhengnian , Cai Quan , Eleuteri Nicholas A. , Zhang Tinghu , Gray Nathanael S. , Fischer Eric S. 
Published: August 2019

AbstractThe investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the activity critically depends on the Cullin RING ligase substrate receptor DCAF15, the molecular details remain elusive. Here we present the cryo-EM structure of the DDB1-DCAF15-DDA1 core ligase complex bound to RBM39 and E7820 at 4.4 Å resolution, together with crystal structures of engineered subcomplexes. We show that DCAF15 adopts a novel fold stabilized by DDA1, and that extensive protein-protein contacts between the ligase and substrate mitigate low affinity interactions between aryl-sulfonamides and DCAF15. Our data demonstrates how aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high affinity ligand, which has broad implications for the de novo discovery of molecular glue degraders.
Ecotone formation through ecological niche construction: the role of biodiversity and species interactions
Authors: Liautaud Kevin , Barbier Matthieu , Loreau Michel 
Published: August 2019

AbstractRapid changes in species composition, also known as ecotones, can result from various causes including rapid changes in environmental conditions, or physiological thresholds. The possibility that ecotones arise from ecological niche construction by ecosystem engineers has received little attention. In this study, we investigate how the diversity of ecosystem engineers, and their interactions, can give rise to ecotones. We build a spatially explicit dynamical model that couples a multispecies community and its abiotic environment. We use numerical simulations and analytical techniques to determine the biotic and abiotic conditions under which ecotone emergence is expected to occur, and the role of biodiversity therein. We show that the diversity of ecosystem engineers can lead to indirect interactions through the modification of their shared environment. These interactions, which can be either competitive or mutualistic, can lead to the emergence of discrete communities in space, separated by sharp ecotones where a high species turnover is observed. Considering biodiversity is thus critical when studying the influence of species-environment interactions on the emergence of ecotones. This is especially true for the wide range of species that have small to moderate effects on their environment. Our work highlights new mechanisms by which biodiversity loss could cause significant changes in spatial community patterns in changing environments.
Linking microbial communities to ecosystem functions: what we can learn from genotype-phenotype mapping in organisms
Authors: Morris Andrew H. , Meyer Kyle M. , Bohannan Brendan J. M. 
Published: August 2019

AbstractMicroorganisms mediate many important ecosystem functions, yet it remains unclear to what extent microbial diversity or community composition is important for determining the rates of ecosystem-scale functions. This uncertainty limits our ability to predict and manage crucial microbially-mediated processes, such as nutrient loss and greenhouse gas emissions. Our lack of understanding stems from the relatively large diversity of microorganisms, the difficulty in directly identifying functional groups, and our limited ability to manipulate microbial community attributes. For this reason, we propose that integrating traditional biodiversity-ecosystem function research with ideas from genotype-phenotype mapping could provide the new perspective our discipline needs. We identify three insights from genotype-phenotype mapping that could be useful for microbial biodiversity-ecosystem function studies: the concept of “agnostic” mapping, the use of more powerful ways to account for multiple comparisons, and the incorporation of covariates into models of ecosystem function. We illustrate the potential for these approaches to elucidate microbial biodiversity-ecosystem function relationships by analyzing a subset of published data measuring methane oxidation rates from incubations of tropical soil. We assert that combining the approaches of traditional biodiversity-ecosystem function research with ideas from genotype-phenotype mapping will not only generate novel hypotheses about how complex microbial communities drive ecosystem function, but also help scientists predict and manage changes to ecosystem functions resulting from human activities.
Gene set inference from single-cell sequencing data using a hybrid of matrix factorization and variational autoencoders
Authors: Lukassen Soeren , Ten Foo Wei , Eils Roland , Conrad Christian 
Published: August 2019

AbstractRecent advances in single-cell RNA sequencing (scRNA-Seq) have driven the simultaneous measurement of the expression of 1,000s of genes in 1,000s of single cells. These growing data sets allow us to model gene sets in biological networks at an unprecedented level of detail, in spite of heterogenous cell populations. Here, we propose an unsupervised deep neural network model that is a hybrid of matrix factorization and conditional variational autoencoders (CVA), which utilizes weights as matrix factorizations to obtain gene sets, while class-specific inputs to the latent variable space facilitate a plausible identification of cell types. This artificial neural network model seamlessly integrates functional gene set inference, experimental batch effect correction, and static gene identification, which we conceptually prove here for three single-cell RNA-Seq datasets and suggest for future single-cell-gene analytics.
Skeletal muscles that actuate sexual displays are specialized forde novoandrogen synthesis
Authors: Schuppe Eric R. , Goller Franz , Fuxjager Matthew J. 
Published: August 2019

AbstractThe gonads (testes) act as the primary organ where androgenic hormones are made to regulate reproductive behavior in male vertebrates. Yet many endocrinologists have also long suspected that other tissues in the body can autonomously synthesize their own androgens to support behavioral output. We examine this idea here by studying whether avian skeletal muscles that actuate elaborate socio-sexual displays are specialized to maintain the molecular machinery otherwise needed for de novo androgen synthesis. Our results show that the vocal organ, or syrinx (SYR), of two songbirds species does in fact express all transporters and enzymes necessary to create androgenic hormones from scratch. This includes genes that encode proteins to mediate rate-limiting steps of steroidogenesis, which are seldom found outside of the gonads. We also show that expression levels of these genes are far greater in the SYR than non-display muscles, matching expression levels found in another extra-gonadal site of steroidogenesis—the brain. Furthermore, we uncover a nearly identical gene expression signature in a woodpecker neck muscle, thelongus colli ventralis(LC). This tissue actuates the bird’s social drum display, which serves the same functions as song. This same study also demonstrates that the elevated expression of steroidogenic genes persists in this neck muscle year-round, suggesting that the LC’s capacity to make androgens is a constitutive trait. Altogether, our findings suggest that muscles involved in sexual display is uniquely specialized to locally make steroid hormones, likely supporting their own role in behavioral production.
Human plasma-like medium improves T lymphocyte activation
Authors: Leney-Greene Michael A. , Boddapati Arun K. , Su Helen C. , Cantor Jason , Lenardo Michael J. 
Published: August 2019

SUMMARYT lymphocytes are critical for effective immunity and the ability to study their behavior in synthetic mediain vitrofacilitates major discoveries in their development, function, and fate. However, the composition of human plasma differs from synthetic media and we hypothesized that these differences could have important effects on cell physiology. We therefore compared T lymphocyte activation in human plasma-like medium (HPLM) to RPMI supplemented with dialyzed FBS (RPMIdFBS) and found that it entrained markedly different transcriptional responses. We also found that the concentration of calcium in RPMIdFBSis six-fold lower than HPLM causing altered T cell activation which could be reversed by calcium addition. Thus, investigators should be cognizant of differences between commonly used media formulations and HPLM which is based on thein vivoplasma environment as these could profoundly affect their experimental results. Physiologic media may be a valuable new way to study immune cells in culture.
SNP-based quantitative deconvolution of biological mixtures: application to the detection of cows with subclinical mastitis by whole genome sequencing of tank milk
Authors: Coppieters Wouter , Karim Latifa , Georges Michel 
Published: August 2019

AbstractBiological products of importance in food (f.i. milk) and medical (f.i. donor blood derived products) sciences often correspond to mixtures of samples contributed by multiple individuals. Identifying which individuals contributed to the mixture and in what proportions may be of interest in several circumstances. We herein present a method that allows to do this by shallow whole genome sequencing of the DNA in mixed samples from hundreds of donors. We demonstrate the efficacy of the approach for the detection of cows with subclinical mastitis by analysis of farms’ tank mixtures containing milk from as many as 500 cows.
Effect of Testosterone on Antler Growth in Male Sambar Deer (Rusaunicolor unicolor) in Horton Plains National Park, Sri Lanka
Authors: Weerasekera D. S. , Rathnasekara N. L. , Nanayakkara D.K.K. , Herath H.M.S.S. , Perera S.J. , Ranawana K.B. 
Published: August 2019

ABSTRACTThis study establishes the relationship between testosterone concentration with the different antler phases in male sambar deer (Rusa unicolor) inhabiting the Horton plains National Park, Sri Lanka (HPNP). Antler growth of sambar was categorized into seven phases; Cast (C), Growing single spike (GS), Growing into a Y as first tine appears (GIY), Growing Velvet begins to harden as third appears(GVT), Growth completed - velvet shedding begins (VS), Hard antler (HA), Casting (CT) based on phenotypic observations. The fecal samples were collected from 10 male sambar deer in each different phases of the antler growth cycle. Fecal testosterone level was estimated using radioimmunoassay (RIA). The results disclose that the dry feces of sambar deer in hard antler phase have a highest mean testosterone concentration of 18.52± 01.87 ng g−1. In the GVT phase the mean testosterone concentration was 09.50±2.01ng g −1, while in the VS phase the mean testosterone concentration increased to 14 ± 01.89 ng g−1. The study also reveals a declination of the testosterone concentration (06.80± 01.20 ng g-1) in CS phase. The C phase had a mean testosterone concentration of 05.52± 0.84 ng g−1. The fecal testosterone levels of the male sambar deer in HPNP changes according to the phase of the antler cycle.SUMMARY STATEMENTTestosterone concentration in fecal pellets of antler phases of male sambar deer in Horton plains National park, Sri Lanka evaluated by Radioimmunoassay kit. The results obtained in this study were agreement with identical research work carried out in other deer species with temperate ancestry.
GABAA receptors are selectively expressed in NG2 glia of the cerebellar white matter
Authors: Emmanuel Labrada-Moncada , Ataulfo Martínez-Torres , Daniel Reyes-Haro 
Published: August 2019

AbstractThe cerebellum is involved in the coordination of movement. Its cellular composition is dominated by GABAergic neuronal types, and glial cells are known to express functional receptors. GABAergic signaling regulates cell proliferation, differentiation, and migration during neurodevelopment. However, little is known about the functional expression of GABA receptors in the cerebellar white matter (WM). Thus, the aim of this study was to test whether glial cells express functional GABA receptors during postnatal development (P7-P9) of cerebellar WM. Immunofluorescence studies showed that half of the astrocytes express GAD67, suggesting that GABA is synthetized by glial cells. Calcium imaging in cerebellar slices revealed that GABA and the GABAA agonist muscimol evoked calcium transients in sulforhodamine B (SRB) negative cells, whereas the GABAB agonist baclofen failed to evoke responses in cerebellar WM. Whole-cell patch-clamp recordings of GFAP+ cells showed dye coupling and a passive current-voltage relation typical of astrocytes. Surprisingly, these cells did not respond to muscimol. Two additional populations were identified as GFAP− cells. The first population showed dye coupling, slow decaying inward and outward currents with no voltage dependence and did not respond to GABAA agonists. The second population showed an outward-rectifying current-voltage relationship and responded to muscimol, but dye coupling was absent. These cells received synaptic input and were NG2+, but evoked calcium waves failed to modulate the frequency of sPSCs or signal directly to NG2 glia. We conclude that GABAA receptor-mediated signaling is selective for NG2 glia in the WM of the cerebellum.
Synergic Combination of Stimulated Emission Depletion Microscopy with Image Scanning Microscopy to Reduce Light Dosage
Authors: Tortarolo Giorgio , Castello Marco , Koho Sami , Vicidomini Giuseppe 
Published: August 2019

AbstractStimulated emission depletion (STED) microscopy is one of the most influential nanoscopy techniques; by increasing the STED beam intensity, it theoretically improves the spatial resolution to any desired value. However, the higher is the dose of stimulating photons, the stronger are the photo-bleaching and photo-toxicity effects, which potentially compromise live-cell and long-term imaging. For this reason the scientific community is looking for strategies to reduce the STED beam intensity needed to achieve a target resolution. Here, we show how the combination of STED microscopy with image scanning microscopy (ISM) meets this request. In particular, we introduce a new STED-ISM architecture – based on our recent single-photon-avalanche-diode (SPAD) detector array – which allows covering the near-diffraction limit resolution range with reduced STED beam intensity. We demonstrate this ability both with simulated data and in live-cell experiments. Because of (i) the minimal changes in the optical architecture of the typical point-scanning STED microscope; (ii) the parameter-free, robust and real-time pixel-reassignment method to obtain the STED-ISM image; (iii) the compatibility with all the recent progresses in STED microscopy, we envisage a natural and rapid upgrade of any STED microscope to the proposed STED-ISM architecture.
Resident microbial communities inhibit growth and antibiotic resistance evolution of Escherichia coli in human gut microbiome samples
Authors: Baumgartner Michael , Bayer Florian , Pfrunder-Cardozo Katia R. , Buckling Angus , Hall Alex R. 
Published: August 2019

AbstractCountering the rise of antibiotic resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g. via resource competition), but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonization by focal E. coli, they also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic resistance evolution of individual species.
Embryonic and foetal expression patterns of the ciliopathy geneCEP164
Authors: Devlin LA , Ramsbottom SA , Overman LM , Lisgo SN , Clowry G , Molinari E , Miles CG , Sayer JA 
Published: August 2019

AbstractNephronophthisis-related ciliopathies (NPHP-RC) are a group of inherited genetic disorders that share a defect in the formation, maintenance or functioning of the primary cilium complex, causing progressive kidney failure and other clinical manifestations. Mutations in centrosomal protein 164 kDa (CEP164), also known asNPHP15, have been identified as a cause of NPHP-RC. Here we have utilised the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) to perform immunohistochemistry studies on human embryonic and foetal tissues to determine the expression patterns ofCEP164during development. Notably expression is widespread, yet defined, in multiple organs including the kidney, retina and cerebellum. Murine studies demonstrated an almost identicalCep164expression pattern. Taken together, this data supports conserved roles forCEP164throughout the development of numerous organs, which we suggest accounts for the multi-system disease phenotype ofCEP164mediated NPHP-RC.