bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical pairs can explain magnetic field and lithium effects on the circadian clock
Authors: Zadeh-Haghighi Hadi , Simon Christoph 
Published: July 2021

AbstractDrosophila’s circadian clock can be perturbed by magnetic fields, as well as by lithium administration. Cryptochromes are critical for the circadian clock. Further, the radical pairs in cryptochrome also can explain magnetoreception in animals. Based on a simple radical pair mechanism model of the animal magnetic compass, we show that both magnetic fields and lithium can influence the spin dynamics of the naturally occurring radical pairs and hence modulate the circadian clock’s rhythms. Using a simple chemical oscillator model for the circadian clock, we show that the spin dynamics influence a rate in the chemical oscillator model, which translates into a change in the circadian period. Our model can reproduce the results of two independent experiments, magnetic fields and lithium effects on the circadian clock. Our model predicts that stronger magnetic fields would shorten the clock’s period. We also predict that lithium influences the clock in an isotope-dependent manner. Furthermore, our model also predicts that magnetic fields and hyperfine interactions modulate oxidative stress. The findings of this work suggest that quantum nature and entanglement of radical pairs might play roles in the brain, as another piece of evidence in addition to recent results on xenon anesthesia and lithium effects on hyperactivity.
Phosphorus availability and arbuscular mycorrhizal fungi limit soil C cycling and influence plant responses to elevated CO2 conditions
Authors: Castañeda-Gómez L. , Powell J.R. , Pendall E. , Carrillo Y. 
Published: July 2021

AbstractEnhanced soil organic matter (SOM) decomposition and organic phosphorus (P) cycling may help sustain plant productivity under elevated CO2 (eCO2) and P-limiting conditions. P-acquisition by arbuscular mycorrhizal (AM) fungi and their impacts on SOM decomposition may become even more relevant in these conditions. Yet, experimental evidence of the interactive effect of AM fungi and P availability influencing altered SOM cycling under eCO2 is scarce and the mechanisms of this control are poorly understood. Here, we performed a pot experiment manipulating P availability, AM fungal presence and atmospheric CO2 levels and assessed their impacts on soil C cycling and plant growth. Plants were grown in chambers with a continuous 13C-input that allowed differentiation between plant- and SOM-derived fractions of respired CO2 (R), dissolved organic C (DOC) and microbial biomass (MBC) as relevant C pools in the soil C cycle. We hypothesised that under low P availability, increases in SOM cycling may support sustained plant growth under eCO2 and that AM fungi would intensify this effect. We found the impacts of CO2 enrichment and P availability on soil C cycling were generally independent of each other with higher root biomass and slight increases in soil C cycling under eCO2 occurring regardless of the P treatment. Contrary to our hypotheses, soil C cycling was enhanced with P addition suggesting that low P conditions were limiting soil C cycling. eCO2 conditions increased the fraction of SOM-derived DOC pointing to increased SOM decomposition with eCO2. Finally, AM fungi increased microbial biomass under eCO2 conditions and low-P without enhanced soil C cycling, probably due to competitive interactions with free-living microorganisms over nutrients. Our findings in this plant-soil system suggest that, contrary to what has been reported for N-limited systems, the impacts of eCO2 and P availability on soil C cycling are independent of each other.
Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler
Authors: Laber Samantha , Strobel Sophie , Mercader Josep-Maria , Dashti Hesam , Ainbinder Alina , Honecker Julius , Garborcauskas Garrett , Stirling David R. , Leong Aaron , Figueroa Katherine , Sinnott-Armstrong Nasa , Kost-Alimova Maria , Deodato Giacomo , Harney Alycen , Way Gregory P. , Saadat Alham , Harken Sierra , Reibe-Pal Saskia , Ebert Hannah , Zhang Yixin , Calabuig-Navarro Virtu , McGonagle Elizabeth , Stefek Adam , Dupuis Josée , Cimini Beth A. , Hauner Hans , Udler Miriam S. , Carpenter Anne E. , Florez Jose C. , Lindgren Cecilia M. , Jacobs Suzanne B. R. , Claussnitzer Melina 
Published: July 2021

SummaryA primary obstacle in translating genetics and genomics data into therapeutic strategies is elucidating the cellular programs affected by genetic variants and genes associated with human diseases. Broadly applicable high-throughput, unbiased assays offer a path to rapidly characterize gene and variant function and thus illuminate disease mechanisms. Here, we report LipocyteProfiler, an unbiased high-throughput, high-content microscopy assay that is amenable to large-scale morphological and cellular profiling of lipid-accumulating cell types. We apply LipocyteProfiler to adipocytes and hepatocytes and demonstrate its ability to survey diverse cellular mechanisms by generating rich context-, and process-specific morphological and cellular profiles. We then use LipocyteProfiler to identify known and novel cellular programs altered by polygenic risk of metabolic disease, including insulin resistance, waist-to-hip ratio and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse phenotypic profiling in lipid-storing cells, and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.
A Sequence-based Antibody Paratope Prediction Model Through Combing Local-Global Information and Partner Features
Authors: Lu Shuai , Li Yuguang , Nan Xiaofei , Zhang Shoutao 
Published: July 2021

AbstractAntibodies are proteins which play a vital role in the immune system by recognizing and neutralizing antigens. The region on the antibody binding to an antigen, known as paratope, mediates antibody-antigen interaction with high affinity and specificity. And the accurate prediction of those regions from antibody sequence contributes to the design of therapeutic antibodies and remains challenging. However, the experimental methods are time-consuming and expensive. In this article, we propose a sequence-based method for antibody paratope prediction by combing local and global information of antibody sequence and partner features from partner antigen sequence. Convolution Neural Networks(CNNs) and a sliding window approach on antibody sequence are used to extract local information. Attention-based Bidirectional Long Short-Term Memory (Att-BLSTM) on antibody sequence are used to extract global information. Also, the partner antigen is vital for paratope prediction, and we employ Att-BLSTM on the partner antigen sequence as well. The outputs of CNNs and Att-BLSTM networks are combined to predict antibody paratope by fully-connected networks. The experiments show that our proposed method achieves superior performance over the state-of-the-art sequenced-based antibody paratope prediction methods on benchmark datasets.
SprayNPray: user-friendly taxonomic profiling of genome and metagenome contigs
Authors: Garber Arkadiy I. , Armbruster Catherine R. , Lee Stella E. , Cooper Vaughn S. , Bomberger Jennifer M. , McAllister Sean M. 
Published: July 2021

AbstractShotgun sequencing of cultured microbial isolates/individual eukaryotes (whole-genome sequencing) and microbial communities (metagenomics) has become commonplace in biology. Very often, sequenced samples encompass organisms spanning multiple domains of life, necessitating increasingly elaborate software for accurate taxonomic classification of assembled sequences. While many software tools for taxonomic classification exist, SprayNPray offers a quick and user-friendly, semiautomated approach, allowing users to separate contigs by taxonomy (and other metrics) of interest. Easy installation, usage, and intuitive output, which is amenable to visual inspection and/or further computational parsing, will reduce barriers for biologists beginning to analyze genomes and metagenomes. This approach can be used for broad-level overviews, preliminary analyses, or as a supplement to other taxonomic classification or binning software. SprayNPray profiles contigs using multiple metrics, including closest homologs from a user-specified reference database, gene density, read coverage, GC content, tetranucleotide frequency, and codon-usage bias. The output from this software is designed to allow users to spot-check metagenome-assembled genomes, identify, and remove contigs from putative contaminants in isolate assemblies, identify bacteria in eukaryotic assemblies (and vice-versa), and identify possible horizontal gene transfer events.
LENG8 regulation of mRNA processing, is responsible for the control of mitochondrial activity
Authors: Zhao Yongxu , Wang Xiaoting , Liu Yuenan , Li Niannian , Wang Shengming , Sun Zhigang , Gao Zhenfei , Zhang Xiaoxu , Mao Linfei , Tang Ru , Xue Wenyue , Li Chunyan , Guan Jian , Yi Hongliang , Zhang Nan , Ding Qiurong , Liu Feng 
Published: July 2021

ABSTRACTThe processing of mRNA is essential for the maintenance of cellular and tissue homeostasis. However, the precise regulation of this process in mammalian cells, remains largely unknown. Here we have found that LENG8 represents the mammalian orthologue of the yeast mRNA processing factor Thp3 and Sac3. We go on to demonstrate that LENG8 binds to mRNAs, associates with components of mRNA processing machinery (the TREX complex) and contributes to mRNA nuclear export to the cytoplasm. Loss of LENG8, leads to aberrant accumulation of poly (A)+ RNA in the nucleus, in both Hela cells and murine fibroblasts. Furthermore, the precipitation of LENG8, is associated with an enrichment of both mRNAs and lncRNAs, and approximately half of these are also bound by the TREX component, THOC1. However, LENG8 preferentially binds mRNAs encoding for mitochondrial proteins and depletion of this processing factor, causes a dramatic breakdown in mitochondrial ultrastructure and a reduction in mitochondrial respiratory activity. Conditional deletion of Leng8 in mouse adipose tissues lead to a decreased body weight, and increased adipose thermogenesis. Our work has found an evolutionarily conserved mRNA processing factor that can control mitochondrial activity.
CoLoRd: Compressing long reads
Authors: Kokot Marek , Gudyś Adam , Li Heng , Deorowicz Sebastian 
Published: July 2021

AbstractThe costs of maintaining exabytes of data produced by sequencing experiments every year has become a major issue in today’s genomics. In spite of the increasing popularity of the third generation sequencing, the existing algorithms for compressing long reads exhibit minor advantage over general purpose gzip. We present CoLoRd, an algorithm able to reduce 3rd generation sequencing data by an order of magnitude without affecting the accuracy of downstream analyzes.
Dynamic surveillance of mosquitoes and their viromes in Wuhan during 2020
Authors: Ren Nanjie , Wang Shunlong , Shi Chenyan , Yu Ping , Zhao Lu , Huang Doudou , Ma Haixia , Xiao Shuqi , Wang Fei , Yuan Zhiming , Xia Han 
Published: July 2021

AbstractMosquitoes are medically important arthropod vectors and harbor a great variety of viruses. The population density, species and virome of mosquitoes varies according to geography and climate. To investigate the dynamic changes in the species composition and diversity of mosquitoes and their viromes in Wuhan, China, a total of 2,345 adult mosquitoes collected from different habitats including an urban residential area, two hospitals, a scenic area, and a pig farm in a rural region from April to October 2020 were subjected to morphological identification, RT-qPCR and metagenomic sequencing. The results indicated that the dominant presence of Culex mosquitoes was observed in both urban regions (90.32%, 1538/1703) and the pig farm (54.98%, 353/642). Viromes of Culex showed dynamic changes during the collection time. Several viruses, such as Culex flavivirus, Alphamesonivirus 1, Hubei mosquito virus 2 and Hubei mosquito virus 4, had seasonal changes and unimodal increases or declines. Other viruses, such as Wuhan mosquito virus 6, Hubei virga-like virus 2 and Zhejiang mosquito virus 3, were stable in all collected Culex and should be potential members of “core viromes”. This study improves the understanding of the dynamic composition of mosquitoes and the viromes they carry and provides useful information for informing mosquito control and mosquito-borne disease prevention strategies.
Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats
Authors: Sep Milou S.C. , Sarabdjitsingh R. Angela. , Geuze Elbert , Joёls Marian 
Published: July 2021

AbstractWhile many people experience potentially threatening events during their life, only a minority develops posttraumatic stress disorder (PTSD). The identification of individuals at risk among those exposed to trauma is crucial for PTSD prevention in the future. Since re-experiencing trauma elements outside of the original trauma-context is a core feature of PTSD, we investigate if the ability to bind memories to their original encoding context (i.e. memory contextualisation) predicts PTSD vulnerability. We hypothesize that pre-trauma neutral memory contextualization (under stress) negatively relates to PTSD-like behavior, in a prospective design using the cut-off behavioral criteria rat model for PTSD. 72 male Sprague Dawley rats were divided in two experimental groups to assess the predictive value of 1) memory contextualization without acute stress (NS-group) and 2) memory contextualization during the recovery phase of the acute stress-response (S-group) for susceptibility to PTSD-like behavior. A powerful extension to regression analysis-path analysis-was used to test this specific hypothesis, together with secondary research questions. Following traumatic predator scent stress, 19.4% of the rats displayed PTSD-like behavior. Results showed a negative relation between pre-trauma memory contextualization and PTSD-like behavior, but only in the NS-group. Pre-trauma memory contextualization was positively related to fear association in the trauma environment, again only in the NS group. If the predictive value of pre-trauma contextualization of neutral information under non-stressful conditions for PTSD susceptibility is replicated in prospective studies in humans, this factor would supplement already known vulnerability factors for PTSD and improve the identification of individuals at risk among the trauma exposed, especially those at high trauma risk such as soldiers deployed on a mission.
A comparative in vitro and in vivo study of osteogenicity by using two biomaterials and two human mesenchymal stem cell subtypes
Authors: Fievet Lucile , Serratrice Nicolas , Brulin Bénédicte , Giraudo Laurent , Véran Julie , Degardin Nathalie , Sabatier Florence , Féron François , Layrolle Pierre 
Published: July 2021

AbstractBone repair induced by stem cells and biomaterials may represent an alternative to autologous bone grafting. Here, we compared the efficiency of two biomaterials - biphasic calcium phosphate (BCP) and bioactive glass (BG) - when loaded with either adult bone marrow mesenchymal stem cells (BM-MSCs) or newborn nasal ecto-mesenchymal stem cells (NE-MSCs), the latter being collected for further repair of lip cleft-associated bone loss. Both cell types display the typical stem cell surface markers CD73+/CD90+/CD105+/nestin, and exhibit the MSC-associated osteogenic, chondrogenic and adipogenic multipotency. NE-MSCs produce less collagen and alkaline phosphatase than BM-MSCs. At the transcript level, NE-MSCs express more abundantly three genes coding for bone sialoprotein, osteocalcin and osteopontin, while BM-MSCs produce extra copies of RUNX2. BM-MSCs and NE-MSCs adhere and survive on BCP and BG. In vivo experiments reveal that bone formation is only observed with BM-MSCs transplanted on BCP biomaterial.
Echidna: integrated simulations of single-cell immune receptor repertoires and transcriptomes
Authors: Han Jiami , Kuhn Raphael , Papadopoulou Chrysa , Agrafiotis Andreas , Kreiner Victor , Shlesinger Danielle , Dizerens Raphael , Hong Kai-Lin , Weber Cédric , Greiff Victor , Oxenius Annette , Reddy Sai T. , Yermanos Alexander 
Published: July 2021

AbstractSingle-cell sequencing now enables the recovery of full-length immune repertoires [B cell receptor (BCR) and T cell receptor (TCR) repertoires], in addition to gene expression information. The feature-rich datasets produced from such experiments require extensive and diverse computational analyses, each of which can significantly influence the downstream immunological interpretations, such as clonal selection and expansion. Simulations produce validated standard datasets, where the underlying generative model can be precisely defined and furthermore perturbed to investigate specific questions of interest. Currently, there is no tool that can be used to simulate a comprehensive ground truth single-cell dataset that incorporates both immune receptor repertoires and gene expression. Therefore, we developed Echidna, an R package that simulates immune receptors and transcriptomes at single-cell resolution. Our simulation tool generates annotated single-cell sequencing data with user-tunable parameters controlling a wide range of features such as clonal expansion, germline gene usage, somatic hypermutation, and transcriptional phenotypes. Echidna can additionally simulate time-resolved B cell evolution, producing mutational networks with complex selection histories incorporating class-switching and B cell subtype information. Finally, we demonstrate the benchmarking potential of Echidna by simulating clonal lineages and comparing the known simulated networks with those inferred from only the BCR sequences as input. Together, Echidna provides a framework that can incorporate experimental data to simulate single-cell immune repertoires to aid software development and bioinformatic benchmarking of clonotyping, phylogenetics, transcriptomics and machine learning strategies.Abstract Figure
Sex-Specific Computational Models of Kidney Function in Patients with Diabetes
Authors: Swapnasrita Sangita , Carlier Aurélie , Layton Anita T. 
Published: July 2021

AbstractThe kidney plays an essential role in homeostasis, accomplished through the regulation of pH, electrolytes and fluids, by the building blocks of the kidney, the nephrons. One of the important markers of the proper functioning of a kidney is the glomerular filtration rate. Diabetes is characterised by an enlargement of the glomerular and tubular size of the kidney, affecting the afferent and efferent arteriole resistance and hemodynamics, ultimately leading to chronic kidney disease. We postulate that the diabetes-induced changes in kidney may exhibit significant sex differences as the distribution of renal transporters along the nephron may be markedly different between women and men, as recently shown in rodents. The goals of this study are to (i) analyze how kidney function is altered in male and female patients with diabetes, and (ii) assess the renal effects, in women and men, of an anti-hyperglycemic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish these goals, we have developed computational models of kidney function, separate for male and female patients with diabetes. The simulation results indicate that diabetes enhances Na+ transport, especially along the proximal tubules and thick ascending limbs, to similar extents in male and female patients, which can be explained by the diabetes-induced increase in glomerular filtration rate. Additionally, we conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Model simulations also suggest that SGLT2 inhibition, which constricts the afferent arteriole to attenuate glomerular hyperfiltration, can then limit Na+-glucose transport, consequently raising luminal [Cl-] at the macula densa and finally restoring the tubuloglomerular feedback signal. By inducing osmotic diuresis in the proximal tubules, SGLT2 inhibition reduces paracellular transport, eventually leading to diuresis and natriuresis. Those effects on urinary excretion are blunted in women, in part due to their higher distal transport capacity.
gmxapi: a GROMACS-native Python interface for molecular dynamics with ensemble and plugin support
Authors: Irrgang M. Eric , Davis Caroline , Kasson Peter M. 
Published: July 2021

AbstractGmxapi provides an integrated, native Python API for both standard and advanced molecular dynamics simulations in GROMACS. The Python interface permits multiple levels of integration with the core GROMACS libraries, and legacy support is provided via an interface that mimics the command-line syntax, so that all GROMACS commands are fully available. Gmxapi has been officially supported since the GROMACS 2019 release and is enabled by default in current versions of the software. Here we describe gmxapi 0.3 and later. Beyond simply wrapping GROMACS library operations, the API permits several advanced operations that are not feasible using the prior command-line interface. First, the API allows custom user plugin code within the molecular dynamics force calculations, so users can execute custom algorithms without modifying the GROMACS source. Second, the Python interface allows tasks to be dynamically defined, so high-level algorithms for molecular dynamics simulation and analysis can be coordinated with loop and conditional operations. Gmxapi makes GROMACS more accessible to custom Python scripting while also providing support for high-level data-flow simulation algorithms that were previously feasible only in external packages.Author SummaryThe gmxapi software provides a Python interface for molecular dynamics simulations in GROMACS. In addition to simply wrapping GROMACS commands, it supports custom user plugin code, ensemble simulation, and data-flow chaining of commands. As such, gmxapi enables the writing and execution of high-level simulation algorithms. The software ships with GROMACS and is freely available under an LGPL2 license.
Lane-maze for preference testing in flies
Authors: Eckert Fabiola Boz , de Brittos Valdati Dhiozer , Neto José Marino , de Toni Daniela Cristina , de Oliveira Cilene Lino 
Published: July 2021

AbstractDrosophila melanogaster is a candidate species to replace rodents in some neurobiological studies, encouraging attempts to develop behavioural tests for these flies. This study aimed to develop a behavioural test to simultaneously evaluate ethological (categorical) aspects of the motor and fluid intake activities, which may be used to assess sucrose preference in flies. For that, a lane-maze was 3D-printed to accommodate up to 14 individual flies in a single trial. Each lane had a capillary filled with 5% sucrose solution attached to one of the extremities. To validate a 5-min lane-maze test, male and female flies (adults, 5-6 days of age) underwent 0, 2, 8 or 20 h of food deprivation (FD, n=9-11/group) before testing. Duration of locomotion, immobility and grooming in the lane or capillary were scored from the video-recorded trials using EthoWatcher software. Minor effects of sex or FD were observed in the behaviours of flies. Independent of sex or FD, flies spent proportionally longer on the capillary than on the lane. Flies exhibited a significantly higher preference than expected for the capillary zone when food-deprived for 2h (males) or 20 h (females). Data suggest that short lane-maze test is a feasibly high throughput assessment of sucrose preference in flies, which may be sexually dimorphic as in other species studied so far.