bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE4is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population
Authors: Garcia Angela R , Finch Caleb E , Gatz Margaret , Kraft Thomas S , Cummings Daniel , Charifson Mia , Rodriguez Daniel Eid , Buetow Kenneth , Beheim Bret , Allayee Hooman , Thomas Gregory S , Stieglitz Jonathan , Gurven Michael , Kaplan Hillard , Trumble Benjamin C 
Published: March 2021

AbstractIn post-industrial settings,APOE4is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, theAPOE4allele confers benefits by reducing baseline innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N=1266),APOE4is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized-LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized-LDL and inflammation which were limited to obese adults. Further,APOE4carriers maintain higher levels of total and LDL cholesterol at low BMIs. These results suggest the relationship betweenAPOE4and lipids is likely beneficial for pathogen-driven immune responses, and unlikely to increase cardiovascular risk in an active subsistence population.
Bumblebees can detect floral humidity
Authors: Harrap Michael J. M. , de Ibarra Natalie Hempel , Knowles Henry D. , Whitney Heather M. , Rands Sean A. 
Published: March 2021

AbstractFloral humidity, a region of elevated humidity proximal to the flower, occurs in many plant species and may add to their multimodal floral displays. So far, the ability to detect and respond to floral humidity cues has been only established for hawkmoths when they locate and extract nectar while hovering in front of some moth-pollinated flowers. To test whether floral humidity can be used by other more widespread generalist pollinators, we designed artificial flowers that presented biologically-relevant levels of humidity similar to those shown by flowering plants. Bumblebees showed a spontaneous preference for flowers which produced higher floral humidity. Furthermore, learning experiments showed that bumblebees are able to use differences in floral humidity to distinguish between rewarding and nonrewarding flowers. Our results indicate that bumblebees are sensitive to different levels of floral humidity. In this way floral humidity can add to the information provided by flowers and could impact pollinator behaviour more significantly than previously thought.Summary statementWe demonstrate for the first time that bumblebees show a preference to elevated floral humidity and can learn to distinguish flowers that differ in floral humidity levels.
Representation learning of RNA velocity reveals robust cell transitions
Authors: Qiao Chen , Huang Yuanhua 
Published: March 2021

AbstractRNA velocity is a promising technique to reveal transient cellular dynamics among a heterogeneous cell population and quantify their transitions from single-cell transcriptome experiments. However, the cell transitions estimated from high dimensional RNA velocity are often unstable or inaccurate, partly due to the high technical noise and less informative projection. Here, we present VeloAE, a tailored representation learning method to learn a low-dimensional representation of RNA velocity on which cell transitions can be robustly estimated. From various experimental datasets, we show that VeloAE can both accurately identify stimulation dynamics in time-series designs and effectively capture the expected cellular differentiation in different biological systems. VeloAE therefore enhances the usefulness of RNA velocity for studying a wide range of biological processes.
Deciphering Bedaquiline and Clofazimine Resistance in Tuberculosis: An Evolutionary Medicine Approach
Authors: Sonnenkalb Lindsay , Carter Joshua , Spitaleri Andrea , Iqbal Zamin , Hunt Martin , Malone Kerri , Utpatel Christian , Cirillo Daniela Maria , Rodrigues Camilla , Nilgiriwala Kayzad S. ,   the CRyPTIC Consortium, Fowler Philip W. , Merker Matthias , Niemann Stefan 
Published: March 2021

AbstractBedaquiline (BDQ) and clofazimine (CFZ) are core drugs for treatment of multidrug resistant tuberculosis (MDR-TB), however, our understanding of the resistance mechanisms for these drugs is sparse which is hampering rapid molecular diagnostics. To address this, we employed a unique approach using experimental evolution, protein modelling, genome sequencing, and minimum inhibitory concentration data combined with genomes from a global strain collection of over 14,151Mycobacterium tuberculosiscomplex isolates and an extensive literature review. Overall, 230 genomic variants causing elevated BDQ and/or CFZ MICs could be discerned, with 201 (87.4%) variants affecting the transcriptional repressor (Rv0678) of an efflux system (mmpS5-mmpL5). Structural modelling of Rv0678 suggests four major mechanisms that confer resistance: impairment of DNA binding, reduction in protein stability, disruption of protein dimerization, and alteration in affinity for its fatty acid ligand. These modelling and experimental techniques will improve personalized medicine in an impending drug resistant era.
Seqpac: A New Framework for small RNA analysis in R using Sequence-Based Counts
Authors: Skog Signe , Örkenby Lovisa , Kugelberg Unn , Tariq Kanwal , Farrants Ann-Kristin Östlund , Öst Anita , Nätt Daniel 
Published: March 2021

ABSTRACTSmall RNA sequencing (sRNA-seq) has become important for studying regulatory mechanisms in many cellular processes. Data analysis remains challenging, mainly because each class of sRNA—such as miRNA, piRNA, tRNA- and rRNA-derived fragments (tRFs/rRFs)—needs special considerations. Analysis therefore involves complex workflows across multiple programming languages, which can produce research bottlenecks and transparency issues. To make analysis of sRNA more accessible and transparent we present seqpac: a tool for advanced group-based analysis of sRNA completely integrated in R. This opens advanced sRNA analysis for Windows users—from adaptor trimming to visualization. Seqpac provides a framework of functions for analyzing a PAC object, which contains 3 standardized tables: sample phenotypic information (P), sequence annotations (A), and a counts table with unique sequences across the experiment (C). By applying a sequence-based counting strategy that maintains the integrity of the fastq sequence, seqpac increases flexibility and transparency compared to other workflows. It also contains an innovative targeting system allowing sequence counts to be summarized and visualized across sample groups and sequence classifications. Reanalyzing published data, we show that seqpac’s fastq trimming performs equal to standard software outside R and demonstrate how sequence-based counting detects previously unreported bias. Applying seqpac to new experimental data, we discovered a novel rRF that was down-regulated by RNA pol I inhibition (anticancer treatment), and up-regulated in previously published data from tumor positive patients. Seqpac is available on github (https://github.com/Danis102/seqpac), runs on multiple platforms (Windows/Linux/Mac), and is provided with a step-by-step vignette on how to analyze sRNA-seq data.
Molecular basis for recognition of the Group A Carbohydrate backbone by the PlyC streptococcal bacteriophage endolysin
Authors: King Harley , Castro Sowmya Ajay , Pohane Amol Arunrao , Scholte Cynthia M. , Fischetti Vincent A. , Korotkova Natalia , Nelson Daniel C. , Dorfmueller Helge C. 
Published: March 2021

AbstractEndolysins are peptidoglycan (PG) hydrolases that function as part of the bacteriophage (phage) lytic system to release progeny phage at the end of a replication cycle. Notably, endolysins alone can produce lysis without phage infection, which offers an attractive alternative to traditional antibiotics. Endolysins from phage that infect Gram-positive bacterial hosts contain at least one enzymatically active domain (EAD) responsible for hydrolysis of PG bonds and a cell wall binding domain (CBD) that binds a cell wall epitope, such as a surface carbohydrate, providing some degree of specificity for the endolysin. Whilst the EADs typically cluster into conserved mechanistic classes with well-defined active sites, relatively little is known about the nature of the CBDs and only a few binding epitopes for CBDs have been elucidated. The major cell wall components of many streptococci are the polysaccharides that contain the polyrhamnose (pRha) backbone modified with species-specific and serotype-specific glycosyl side chains. In this report, using molecular genetics, microscopy, flow cytometry and lytic activity assays, we demonstrate the interaction of PlyCB, the CBD subunit of the streptococcal PlyC endolysin, with the pRha backbone of the cell wall polysaccharides, Group A Carbohydrate (GAC) and serotypec-specific carbohydrate (SCC) expressed by the Group A Streptococcus andStreptococcus mutans, respectively.
Optimal Transport improves cell-cell similarity inference in single-cell omics data
Authors: Huizing Geert-Jan , Peyré Gabriel , Cantini Laura 
Published: March 2021

AbstractThe recent advent of high-throughput single-cell molecular profiling is revolutionizing biology and medicine by unveiling the diversity of cell types and states contributing to development and disease. The identification and characterization of cellular heterogeneity is typically achieved through unsupervised clustering, which crucially relies on a similarity metric.We here propose the use of Optimal Transport (OT) as a cell-cell similarity metric for single-cell omics data. OT defines distances to compare, in a geometrically faithful way, high-dimensional data represented as probability distributions. It is thus expected to better capture complex relationships between features and produce a performance improvement over state-of-the-art metrics. To speed up computations and cope with the high-dimensionality of single-cell data, we consider the entropic regularization of the classical OT distance. We then extensively benchmark OT against state-of-the-art metrics over thirteen independent datasets, including simulated, scRNA-seq, scATAC-seq and single-cell DNA methylation data. First, we test the ability of the metrics to detect the similarity between cells belonging to the same groups (e.g. cell types, cell lines of origin). Then, we apply unsupervised clustering and test the quality of the resulting clusters.In our in-depth evaluation, OT is found to improve cell-cell similarity inference and cell clustering in all simulated and real scRNA-seq data, while its performances are comparable with Pearson correlation in scATAC-seq and single-cell DNA methylation data. All our analyses are reproducible through the OT-scOmics Jupyter notebook available athttps://github.com/ComputationalSystemsBiology/OT-scOmics.
Cellar: Interactive single cell data annotation tool
Authors: Hasanaj Euxhen , Wang Jingtao , Sarathi Arjun , Ding Jun , Bar-Joseph Ziv 
Published: March 2021

AbstractSeveral recent technologies and platforms enable the profiling of various molecular signals at the single-cell level. A key question for all studies using such data is the assignment of cell types. To improve the ability to correctly assign cell types in single and multi-omics sequencing and imaging single-cell studies, we developed Cellar. This interactive software tool supports all steps in the analysis and assignment process. We demonstrate the advantages of Cellar by using it to annotate several HuBMAP datasets from multi-omics single-cell sequencing and spatial proteomics studies. Cellar is freely available and includes several annotated reference HuBMAP datasets.Availabilityhttps://data.test.hubmapconsortium.org/app/cellar
Foxes engineer hotspots of wildlife activity on the nutrient-limited Arctic tundra
Authors: Zhao Shu-Ting , Johnson-Bice Sean M. , Roth James D. 
Published: March 2021

AbstractPredators largely affect ecosystems through trophic interactions, but they also can have indirect effects by altering nutrient dynamics and acting as ecosystem engineers. Arctic foxes (Vulpes lagopus) are ecosystem engineers that concentrate nutrients on their dens, creating biogeochemical hotspots with lush vegetation on the nutrient-limited tundra. Red foxes (V. vulpes) similarly engineer subarctic environments through their denning behavior, and have recently expanded onto the tundra where they now often occupy historical Arctic fox dens. We evaluated the impact of fox denning activity on the spatial behavior of other tundra wildlife by comparing predator and herbivore visits to 12 natal dens and adjacent control sites over two years using camera traps in northeastern Manitoba, where both fox species are sympatric. Both the capture rates and species richness of wildlife were significantly greater at fox dens relative to control sites. Predators were detected almost exclusively on dens occupied by foxes, where they were observed investigating and scavenging prey remains (carrion, feathers), suggesting carcass presence or fox presence attracts predators to den sites. Caribou (Rangifer tarandus) also visited dens more often than control sites, likely attracted by the enhanced vegetation typically found on dens. Our results suggest fox ecosystem engineering affects the spatial distribution of herbivores by enriching vegetation at dens, and other predators by providing carrion. Understanding how predators affect other organisms via non-trophic interactions provides an enriched view of their functional roles within ecosystems.
Multi-substrate DNA stable isotope probing reveals guild structure in bacterially mediated soil carbon cycling
Authors: Barnett Samuel E. , Youngblut Nicholas D. , Koechli Chantal N. , Buckley Daniel H. 
Published: March 2021

AbstractSoil microorganisms determine the fate of soil organic matter (SOM), and their activities comprise a major component of the global carbon (C) cycle. We employed a multi-substrate DNA-stable isotope probing experiment to track bacterial assimilation of C derived from distinct sources that varied in bioavailability. This approach allowed us to measure microbial contributions to SOM processing by measuring the C assimilation dynamics of diverse microorganisms as they interact within soil. We identified and tracked 1,286 bacterial taxa that assimilated13C in an agricultural soil over a period of 48 days. Overall13C-assimilation dynamics of bacterial taxa, defined by the source and timing of the13C they assimilated, exhibited low phylogenetic conservation. We identified bacterial guilds comprised of taxa that had similar13C assimilation dynamics. We show that C source bioavailability explained significant variation in both C mineralization dynamics and guild structure. In addition, guild structure explained significant variation in bacterial growth dynamics. We demonstrate that the observed guild structure is consistent with predictions made by bacterial life history theory. We also demonstrate that the guild structure explains significant variation in the biogeographical distribution of bacteria at continental and global scales. We interpret these findings in the context of bacterial life history strategies and their relationship to terrestrial C-cycling.
Application of HPMCAS-coated Ctx(Ile21)-Ha peptide microparticles as a potential use to prevent systemic infection caused bySalmonellaEnteritidis in poultry
Authors: Roque Borda Cesar Augusto , de Mesquita Souza Saraiva Mauro , Monte Daniel F. M. , Rodrigues Alves Lucas Bocchini , de Almeida Adriana Maria , Ferreira Taísa Santiago , de Lima Túlio Spina , Benevides Valdinete Pereira , Cabrera Julia Memrava , Meneguin Andréia Bagliotti , Chorilli Marlus , Junior Angelo Berchieri , Vicente Eduardo Festozo 
Published: March 2021

ABSTRACTThe transmission ofSalmonellaEnteritidis (SE) in poultry is most often by the fecal-oral route, which can be attributed to the population density. Consequently, the pathogen triggers stress response and virulence factors deploying it to survive in hosts. Therefore, this study proposed to evaluate HPMCAS-coated microparticles containing the Ctx(Ile21)-Ha antimicrobial peptide against SE in laying hens chicks’ infection model to determine whether Ctx(Ile21)-Ha-utilization confers a benefit in the intestinal lumen, as well as whether limits systemic infection. Importantly, while assessing whether AMP utilization confers reduction of SE in liver, it was noted that there was statistical significance between groups A (control, no Ctx(Ile21)-Ha peptide) and B (2.5 mg of Ctx(Ile21)-Ha/kg) at 2 dpi, potentially indicating the Ctx(Ile21)-Ha effectiveness in the first stage of infection by SE. Remarkably, it was also detected a statistical significance (p-value <0.0001) with lower counts of SE (∼ 0 CFU) in livers at 5, 7, and 14 dpi, regardless of Ctx(Ile21)-Ha dosage (2.5 mg or 5 mg/kg - group C). By using Chi-square test, the AMP effect on SE fecal excretion was evaluated. In this regard, it was noticed statistical significance (p< 0.05) among groups B and C in comparison with control group A, since those groups had lower bacterial excretion along 21 days. In summary, the role of HPMCAS-Ctx(Ile21)-Ha peptide microcapsules againstS. Enteritidis in laying hen chicks infection model was unraveled, providing a satisfactory results against this pathogen.
An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single cell resolution
Authors: Lindner Andreas Ulrich , Salvucci Manuela , McDonough Elizabeth , Cho Sanghee , Stachtea Xanthi , O’Connell Emer Patsy , Corwin Alex D , Santamaria-Pang Alberto , Carberry Steven , Fichtner Michael , Van Schaeybroeck Sandra , Laurent-Puig Pierre , Burke John P , McNamara Deborah A , Lawler Mark , Soop Anup , Graf John F , Rehm Markus , Dunne Philip , Longley Daniel B , Ginty Fiona , Prehn Jochen HM 
Published: March 2021

AbstractCancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells and quantification of 20 cell lineage and apoptosis proteins. Ordinary differential equation-based modelling of apoptosis sensitivity at single cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. We identified an enrichment for BCL2 in immune, and BAK, SMAC and XIAP in cancer cells. ODE-based modelling at single cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, with significant inter- and intra-tumor heterogeneity. However, we did not find increased spatial heterogeneity of apoptosis signaling in cancer cells, suggesting that such heterogeneity is an intrinsic, non-genomic property not increased by the process of malignant transformation.
Revisiting the source of wilt symptoms: X-ray microcomputed tomography provides direct evidence thatRalstoniabiomass clogs xylem vessels
Authors: Ingel Brian , Caldwell Denise , Duong Fiona , Parkinson Dilworth Y. , McCulloh Katherine A. , Iyer-Pascuzzi Anjali S. , McElrone Andrew J. , Lowe-Power Tiffany M. 
Published: March 2021

AbstractPlant pathogenicRalstoniacause wilt diseases by colonizing xylem vessels and disrupting water transport. Due to the abundance ofRalstoniacells in vessels, the dogma is that bacterial biomass clogs vessels and reduces the flow of xylem sap. However, the physiological mechanism of xylem disruption during bacterial wilt disease is untested. Using a tomato andRalstonia pseudosolanacearumGMI1000 model, we visualized and quantified the spatiotemporal dynamics of xylem disruption during bacterial wilt disease. First, we measured stomatal conductance of leaflets on mock-inoculated and wilt-symptomatic plants. Wilted leaflets had reduced stomatal conductance, as did turgid leaflets located on the same petiole as wilted leaflets. Next, we used X-ray microcomputed tomography (X-ray microCT) and light microscopy to differentiate between mechanisms of xylem disruption: blockage by bacterial biomass, blockage by vascular tyloses, or sap displacement by gas embolisms. We imaged stems on plants with intact roots and leaves to quantify embolized vessels. Embolized vessels were rare, but there was a slight trend of increased vessel embolisms in infected plants with low bacterial population sizes. To test the hypothesis that vessels are clogged during bacterial wilt, we imaged excised stems after allowing the sap to evaporate during a brief dehydration. Most xylem vessels in mock-infected plants emptied their contents after excision, but non-conductive clogged vessels were abundant in infected plants by 2 days post infection. At wilt onset when bacterial populations exceeded 5×108cfu/g stem tissue, approximately half of the xylem vessels were clogged with electron-dense bacterial biomass. We found no evidence of tyloses in the X-ray microCT reconstructions or light microscopy on the preserved stems. Bacterial blockage of vessels appears to be the principal cause of vascular disruption duringRalstoniawilt.
Platinized graphene fiber electrodes revealed differential activity in terminal splenic neurovascular plexi supporting a direct spleen-vagus communication
Authors: González-González María A. , Bendale Geetanjali , Wang K , Wallace Gordon G. , Romero-Ortega Mario 
Published: March 2021

AbstractNeural interfacing nerve fascicles along the splenic neurovascular plexi (SNVP) is needed to better understand the spleen physiology, and for selective neuromodulation of this major organ. However, the small size and anatomical location have proven to be a significant challenge. Here, we use a reduced liquid crystalline graphene oxide (rGO) fiber coated with platinum (Pt) as a super-flexible suture-like electrode to interface multiple SNVP. The Pt-rGO fibers were used as handover knot electrodes over the small plexi, allowing sensitive recording from the splenic nerve (SN) terminal branches. Asymmetric defasciculation of the SN branches was revealed by electron microscopy, and the functional compartmentalization in spleen innervation was evidenced in response to hypoxia and pharmacological modulation of mean arterial pressure. We demonstrate that electrical stimulation of cervical and subdiaphragmatic vagus nerve (VN), evoked direct activity in a subset of SN terminal branches, providing evidence for a direct VN control over the spleen. This notion was supported by tract-tracing of SN branches, revealing an unconventional direct spleen-VN projection. High-performance Pt-rGO fiber electrodes, may be used for the fine neural modulation of other small neurovascular plexi at the point of entry of the organs as a bioelectronic medical alternative.