bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rewiring of gene expression in circulating white blood cells is associated with pregnancy outcome in heifers (Bos taurus)
Authors: Moorey Sarah E. , Walker Bailey N. , Elmore Michelle F. , Elmore Joshua B. , Rodning Soren P. , Biase Fernando H. 
Published: March 2020

ABSTRACTInfertility is a challenging phenomenon in cattle that reduces the sustainability of beef production worldwide. Here, we tested the hypothesis that gene expression profiles of protein-coding genes expressed in peripheral white blood cells (PWBCs), and circulating micro RNAs in plasma, are associated with female fertility, measured by pregnancy outcome. We drew blood samples from 17 heifers on the day of artificial insemination and analyzed transcript abundance for 10496 genes in PWBCs and 290 circulating micro RNAs. The females were later classified as pregnant to artificial insemination, pregnant to natural breeding or not pregnant. We identified 1860 genes producing significant differential coexpression (eFDR<0.002) based on pregnancy outcome. Additionally, 237 micro RNAs and 2274 genes in PWBCs presented differential coexpression based on pregnancy outcome. Furthermore, using a machine learning prediction algorithm we detected a subset of genes whose abundance could be used for blind categorization of pregnancy outcome. Our results provide strong evidence that transcript abundance in circulating white blood cells is associated with fertility in heifers.
Regulatory Sharing Between Estrogen Receptor α Bound Enhancers
Authors: Carleton Julia B. , Ginley-Hidinger Matthew , Berrett Kristofer C. , Layer Ryan M. , Quinlan Aaron R. , Gertz Jason 
Published: March 2020

AbstractThe human genome encodes an order of magnitude more gene expression enhancers than promoters, suggesting that most genes are regulated by the combined action of multiple enhancers. We have previously shown that neighboring estrogen-responsive enhancers, which are approximately 5,000 basepairs apart, exhibit complex synergistic contributions to the production of an estrogenic transcriptional response. Here we sought to determine the molecular underpinnings of the observed enhancer cooperativity. We generated genetic deletions of individual estrogen receptor α (ER) bound enhancers and found that enhancers containing full estrogen response element (ERE) motifs control ER binding at neighboring sites, while enhancers with pre-existing histone acetylation/accessibility confer a permissible chromatin environment to the neighboring enhancers. Genome engineering revealed that a cluster of two enhancers with half EREs could not compensate for the lack of a full ERE site within the cluster. In contrast, two enhancers with full EREs produced a transcriptional response greater than the wild-type locus. By swapping genomic sequences between enhancers, we found that the genomic location in which a full ERE resides strongly influences enhancer activity. Our results lead to a model in which a full ERE is required for ER recruitment, but the presence of a pre-existing active chromatin environment within an enhancer cluster is also needed in order for estrogen-driven gene regulation to occur.
The impact of compound library size on the performance of scoring functions for structure-based virtual screening
Authors: Fresnais Louison , Ballester Pedro J. 
Published: March 2020

AbstractLarger training datasets have been shown to improve the accuracy of Machine Learning (ML)-based Scoring functions (SFs) for Structure-Based Virtual Screening (SBVS). In addition, massive test sets for SBVS, known as ultra-large compound libraries, have been demonstrated to enable the fast discovery of selective drug leads with at least nanomolar potency. This proof-of-concept was carried out on two targets using a single docking tool along with its SF. It is thus unclear whether this high level of performance would generalise to other targets, docking tools and SFs.We found that screening a larger compound library results in more potent actives being identified in all six additional targets using a different docking tool along with its classical SF. Furthermore, we established that a way to improve the potency of the retrieved molecules further is to rank them with more accurate ML-based SFs (we found this to be true in four of the six targets, the difference was not significant in the remaining two targets). A three-fold increase in average hit rate across targets was also achieved by the ML-based SFs. Lastly, we observed that classical and ML-based SFs often find different actives, which supports using both types of SFs on those targets.Contactpedro.ballester@inserm.frSupplementary informationan online-only supplementary results file is enclosed.Biographical NoteL. Fresnais carried out a master research project directly supervised by P.J Ballester and he will soon be starting a PhD.P.J Ballester has been working on virtual screening for over 15 years now. He is group leader and research scientist at cancer research centre of INSERM, the French National Institute of Health & Medical Research.
A Graphic User Interface (GUI) to build a cost-effective customizable 3D printed Prosthetic Hand
Authors: Lázaro-Guevara J. , Gondokaryono R. , González L. , Garrido K. , Sujumnong N. , Wee A. , Miscione J. 
Published: March 2020

AbstractThis project aims to create a tool that allows medical staff to use an intuitive graphical user interface (GUI) based application to generate STL models of a customizable prosthetic hand, that can be 3d printed to fit a specific patient’s hand size. Since the whole process of adjust and adapt the prosthetics devices could consume most of the resources of small medical attention centers. And the necessity to adapt the prosthetic devices is highly relevant when these are intended to be used by the pediatric population. This software creates a customizable parametric 3d model for a trans-radial prosthetic hand and all its necessary components for 3d print and assemble it. The software is intended to be operated by non-trained staff, reducing the costs of remodeling or adapting the original model to fit the necessity of a patient, allowing to produce personalized prosthetic devices in a cost-effective manner with an effortless customization approach. This will allow that medical practitioners with a lack of technical background to get involved in spreading 3D-prosthetics. Also, using open-source parametric 3D-models could lead to existing 3D-prosthetic projects that will adopt this method of customization, allowing the expansion of 3D-printed prosthetics at developing-countries reaching all needing patients. Ultimately, this tool will allow the medical staff to focus on adjusting or replacing the prosthetic devices more often than previously, due to be considered too expensive..
Phylogenomics of the leaf-footed bug subfamily Coreinae (Hemiptera: Coreidae): applicability of ultraconserved elements at shallower depths
Authors: Forthman Michael , Miller Christine W. , Kimball Rebecca T. 
Published: March 2020

AbstractBaits targeting invertebrate ultraconserved elements (UCEs) are becoming more common for phylogenetic studies. Recent studies have shown that invertebrate UCEs typically encode proteins — and thus, are functionally different from more conserved vertebrate UCEs —can resolve deep divergences (e.g., superorder to family ranks). However, the ability of the invertebrate UCE baits to robustly resolve relationships at shallower phylogenetic scales (i.e., tribes and congeners) has been generally limited to Coleoptera and Hymenoptera. Here, we assessed the ability of a recently designed Hemiptera UCE bait set to reconstruct more recent phylogenetic relationships in the largest leaf-footed bug subfamily, the Coreinae (Hemiptera: Coreidae), using a taxon-rich sample representing 21 of the 32 coreine tribes. Many well-supported, novel relationships were congruent in maximum likelihood and summary coalescent analyses. We also found evidence for the para- and polyphyly of several tribes and genera of Coreinae, as well as the subfamilies Coreinae and Meropachyinae. Our study, along with other recent UCE studies, provides evidence that UCEs can produce robust and novel phylogenetic hypotheses at various scales in invertebrates. Additionally, we used different DNA extraction and target enrichment protocols and recovered more UCE data using a touch-down hybridization approach.
Genomics of sex allocation in the parasitoid waspNasonia vitripennis
Authors: Pannebakker Bart A. , Cook Nicola , van den Heuvel Joost , van de Zande Louis , Shuker David M. 
Published: March 2020

AbstractBackgroundWhilst adaptive facultative sex allocation has been widely studied at the phenotypic level across a broad range of organisms, we still know remarkably little about its genetic architecture. Here, we explore the genome-wide basis of sex ratio variation in the parasitoid waspNasonia vitripennis, perhaps the best studied organism in terms of sex allocation, and well known for its response to local mate competition (LMC).ResultsWe performed a genome-wide association study (GWAS) for single foundress sex ratios using iso-female lines derived from the recently developed outbredN. vitripennislaboratory strain HVRx. The iso-female lines capture a sample of the genetic variation in HVRx and we present them as the first iteration of theNasonia vitripennisGenome Reference Panel (NVGRP 1.0). This panel provides an assessment of the standing genetic variation for sex ratio in the study population. Using the NVGRP, we discovered a cluster of 18 linked SNPs, encompassing 9 annotated loci associated with sex ratio variation. Furthermore, we found evidence that sex ratio has a shared genetic basis with clutch size on three different chromosomes.ConclusionsOur approach provides a thorough description of the quantitative genetic basis of sex ratio variation inNasoniaat the genome level and reveals a number of inter-related candidate loci underlying sex allocation regulation.
Uveal melanoma cells use ameboid and mesenchymal mechanisms of cell motility crossing the endothelium
Authors: Onken Michael D. , Cooper John A. 
Published: March 2020

SUMMARYUveal melanomas (UM) are malignant cancers arising from the pigmented layers of the eye. UM cells spread through the bloodstream, and circulating UM cells are detectable in patients before metastases appear. Extravasation of UM cells, notably transendothelial migration (TEM), is a key step in formation of metastases. UM cells execute TEM via a stepwise process of intercalation into the endothelial monolayer involving the actin-based processes of ameboid blebbing and mesenchymal lamellipodial protrusion. UM cancers are driven by oncogenic mutations in Gαq/11, which activate TRIO, a guanine nucleotide exchange factor (GEF) for RhoA and Rac1. Pharmacologic inhibition of Gαq/11 in UM cells reduced TEM. Inhibition of the RhoA pathway blocked amoeboid motility but led to enhanced TEM; in contrast, inhibition of the Rac1 pathway decreased mesenchymal motility and reduced TEM. Inhibition of Arp2/3 also inhibited mesenchymal motility, but invasion was less affected; in this case, the amoeboid blebbing behavior of the cells led to transmigration without intercalation, a direct mechanism similar to that of immune cells. BAP1-deficient (+/−) UM subclones displayed motility behavior and increased levels of TEM, similar to effects of RhoA inhibitors. We conclude that RhoA and Rac1 signaling pathways, downstream of oncogenic Gαq/11, combine with pathways regulated by BAP1 to control the motility and transmigration of UM cells.
Streamlined freshwater bacterioplanktonNanopelagicales(acI) and “Ca. Fonsibacter” (LD12) thrive in functional cohorts
Authors: Mondav Rhiannon , Bertilsson Stefan , Buck Moritz , Langenheder Silke , Lindström Eva S. , Garcia Sarahi L 
Published: March 2020

ABSTRACTWhile fastidious microbes can be abundant and ubiquitous in their natural communities, many fail to grow axenically in laboratories due to auxotrophies or other dependencies. To overcome auxotrophies these microbes rely on their surrounding cohort. A cohort may consist of kin (ecotypes) or more distantly related organisms (community) with the cooperation being reciprocal or non-reciprocal, and expensive (Black Queen hypothesis) or costless (byproduct). These metabolic partnerships (whether at single species population or community level) enable dominance by and coexistence of these lineages in nature. Here we examine the relevance of these cooperation models to explain the abundance and ubiquity of the dominant fastidious bacterioplankton of a dimictic mesotrophic freshwater lake. Using both culture dependent (minimalist mixed cultures) and culture independent (SSU rRNA gene time series and environmental metagenomics) methods we independently identified the primary cohorts ofActinobacterialgenera “Ca. Planktophila” (acI-A) and “Ca. Nanopelagicus” (acI-B), and theProteobacterialgenus “Ca. Fonsibacter” (LD12). While “Ca. Planktophila” and “Ca. Fonsibacter” had no correlation in their natural habitat, they have the potential to be complementary in laboratory settings. We also investigated the bi-functional catalase-peroxidase enzyme KatG (a common good which “Ca. Planktophila” is dependent upon) and its most likely providers in the lake. Further we found that while ecotype and community cooperation combined may explain “Ca. Planktophila” population abundance, the success of “Ca. Nanopelagicus” and “Ca. Fonsibacter” is better explained as a community byproduct. Ecotype differentiation of “Ca. Fonsibacter” as a means of escaping predation was supported but not for overcoming auxotrophies.IMPORTANCEThis study examines evolutionary and ecological relationships of three of the most ubiquitous and abundant freshwater bacterial genera: “Ca. Planktophila” (acI-A), “Ca. Nanopelagicus” (acI-B), and “Ca. Fonsibacter” (LD12). Due to high abundance, these genera might have a significant influence on nutrient cycling in freshwaters worldwide and this study adds a layer of understanding to how seemingly competing clades of bacteria can co-exist by having different cooperation strategies. Our synthesis ties together network and ecological theory with empirical evidence and lays out a framework for how the functioning of populations within complex microbial communities can be studied.
Faithful Scanning Electron Microscopic (SEM) visualization of 3D printed alginate-based scaffolds
Authors: Koch Marcus , Włodarczyk-Biegun Małgorzata K. 
Published: March 2020

AbstractThe morphological characterization of 3D printed hydrogel-based scaffolds is essential for monitoring their size, shape, surface texture and internal structure. Among other microscopic techniques, Scanning Electron Microscopy (SEM) is capable of visualizing nearly all kinds of materials at different length scales, with exceptional precision, if investigation under vacuum is possible. However, due to the high water content of hydrogel-based scaffolds and the connected volume change after drying, special preparation techniques are necessary to stabilize the 3D architecture when imaged by SEM. Here we present a straightforward cryo-SEM technique to visualize 3D printed hydrogel-based alginate scaffolds. By use of a homemade cryo-SEM holder and plunge-freezing in liquid ethane, scaffolds are visualized from the top and cross-sectional view at different magnifications. The proposed method is compared with SEM imaging in different modes (cyro-SEM, conventional SEM, ESEM) following other commonly used sample preparation techniques, such as plunging in liquid nitrogen, air-drying, freeze-drying and plunging in liquid ethane after graded dehydration. These approaches, except ESEM, lead to shrinkage, deformation, distortion or disintegration of the scaffolds and consequently give rise to artifacts in imaging. The presented results indicate that cryo-SEM after plunging in liquid ethane allows for the most faithful and time-efficient visualization of 3D printed alginate scaffolds.
Characterization of a Large Pericentric Inversion in Plateau Fence Lizards (Sceloporus tristichus): Evidence from Chromosome-scale Genomes
Authors: Bedoya Ana M. , Leaché Adam D. 
Published: March 2020

AbstractSpiny lizards in the genusSceloporusare a model system among squamate reptiles for studies of chromosomal evolution. While most pleurodont iguanians retain an ancestral karyotype formula of 2n=36 chromosomes,Sceloporusexhibits substantial karyotype variation ranging from 2n=22 to 2n=46 chromosomes. In this study, we present two annotated chromosome-scale genome assemblies for the Plateau Fence Lizard (Sceloporus tristichus) in order to facilitate research on the role of pericentric inversion polymorphisms on adaptation and speciation. Based on previous karyotype work using conventional staining, theS. tristichusgenome is characterized as 2n=22 with 6 pairs of macrochromosomes and 5 pairs of microchromosomes with a large pericentric inversion polymorphism on chromosome seven that is geographically variable. We provide annotated, chromosome-scale genomes for two lizards located at opposite ends of a dynamic hybrid zone that are each fixed for different inversion polymorphisms. The assembled genomes are 1.84 to 1.87 Gb (1.72 Gb for scaffolds mapping to chromosomes) with a scaffold N50 of 267.5 Mb. Functional annotation of the genomes resulted in 65,417 annotated genes, 16,426 of which were deduced to have a function. We confirmed the presence of a 4.62 Mb pericentric inversion on chromosome seven, which contains 59 annotated coding genes with known functions. These new genomic resources provide opportunities to perform genomic scans and investigate the formation and spread of pericentric inversions in a naturally occurring hybrid zone.
Improving the accessibility and transferability of machine learning algorithms for identification of animals in camera trap images: MLWIC2
Authors: Tabak Michael A. , Norouzzadeh Mohammad S. , Wolfson David W. , Newton Erica J. , Boughton Raoul K. , Ivan Jacob S. , Odell Eric A. , Newkirk Eric S. , Conrey Reesa Y. , Stenglein Jennifer L. , Iannarilli Fabiola , Erb John , Brook Ryan K. , Davis Amy J. , Lewis Jesse S. , Walsh Daniel P. , Beasley James C. , VerCauteren Kurt C. , Clune Jeff , Miller Ryan S. 
Published: March 2020

AbstractMotion-activated wildlife cameras (or “camera traps”) are frequently used to remotely and non-invasively observe animals. The vast number of images collected from camera trap projects have prompted some biologists to employ machine learning algorithms to automatically recognize species in these images, or at least filter-out images that do not contain animals. These approaches are often limited by model transferability, as a model trained to recognize species from one location might not work as well for the same species in different locations. Furthermore, these methods often require advanced computational skills, making them inaccessible to many biologists.We used 3 million camera trap images from 18 studies in 10 states across the United States of America to train two deep neural networks, one that recognizes 58 species, the “species model,” and one that determines if an image is empty or if it contains an animal, the “empty-animal model.”Our species model and empty-animal model had accuracies of 96.8% and 97.3%, respectively. Furthermore, the models performed well on some out-of-sample datasets, as the species model had 91% accuracy on species from Canada (accuracy range 36-91% across all out-of-sample datasets) and the empty-animal model achieved an accuracy of 91-94% on out-of-sample datasets from different continents.Our software addresses some of the limitations of using machine learning to classify images from camera traps. By including many species from several locations, our species model is potentially applicable to many camera trap studies in North America. We also found that our empty-animal model can facilitate removal of images without animals globally. We provide the trained models in an R package (mlwic2: Machine Learning for Wildlife Image Classification in R), which contains Shiny Applications that allow scientists with minimal programming experience to use trained models and train new models in six neural network architectures with varying depths.
Phenotypic parallelism during experimental adaptation of a free-living bacterium to the zebrafish gut
Authors: Lebov Jarrett F. , Schlomann Brandon H. , Robinson Catherine D. , Bohannan Brendan J. M. 
Published: March 2020

AbstractDespite the fact that animals encounter a plethora of bacterial species throughout their lives, only a subset are capable of colonizing vertebrate digestive tracts, and these bacteria can profoundly influence the health and development of their animal hosts. However, it is still unknown how bacteria evolve symbioses with animal hosts, and this process is central to both the assembly and function of gut bacterial communities. Therefore, we used experimental evolution to study a free-living bacterium as it adapts to a novel vertebrate host. We serially passaged replicate populations ofShewanella oneidensis, through the digestive tracts of larval zebrafish (Danio rerio). After only 20 passages, representing approximately 200 bacterial generations, isolates from replicate evolved populations displayed an improved ability to colonize larval zebrafish digestive tracts during competition against their unpassaged ancestor. Upon sequencing the genomes of these evolved isolates, we discovered that the two isolates with the highest mean competitive fitness accumulated unique sets of mutations. We characterized the swimming motility and aggregation behavior of these isolates, as these phenotypes have previously been shown to alter host-microbe interactions. Despite exhibiting different biofilm characteristics, both isolates evolved augmented swimming motility. These enhancements are consistent with expectations based on the behavior of a closely relatedShewanellastrain previously isolated from the zebrafish digestive tract and suggest that our evolved isolates are pursuing a convergent adaptive trajectory with this zebrafish isolate. In addition, parallel enhancements in swimming motility among isolates from independently adapted populations implicates increased dispersal as an important factor in facilitating the onset of host association. Our results demonstrate that free-living bacteria can rapidly improve their associations with vertebrate hosts.