bluuebunny/crossref_metadata_2025_split huggingface dataset:
A causal role for the right frontal eye fields in value comparison
Authors: Mitsumasu Andres , Krajbich Ian , Polania Rafael , Ruff Christian C. , Fehr Ernst 
Published: March 2021

AbstractRecent studies have suggested close functional links between visual attention and decision making. This suggests that the corresponding mechanisms may interface in brain regions known to be crucial for guiding visual attention – such as the frontal eye field (FEF). Here, we combined brain stimulation, eye tracking and computational approaches to explore this possibility. We show that inhibitory transcranial magnetic stimulation (TMS) over the right FEF has a causal impact on decision-making, reducing the effect of gaze dwell time on choice while also increasing reaction times. We computationally characterize this putative mechanism by using the attentional drift diffusion model (aDDM), which reveals that FEF inhibition reduces the relative discounting of the non-fixated option in the comparison process. Our findings establish an important causal role of the right FEF in choice, elucidate the underlying mechanism, and provide support for one of the key causal hypotheses associated with the aDDM.
Phenotyping heart failure using model-based analysis and physiology-informed machine learning
Authors: Jones Edith , Randall E. Benjamin , Hummel Scott L. , Cameron David , Beard Daniel A. , Carlson Brian E. 
Published: March 2021

AbstractTo determine the underlying mechanistic differences between diagnoses of Heart Failure (HF) and specifically heart failure with reduced and preserved ejection fraction (HFrEF & HFpEF), a closed loop model of the cardiovascular system coupled with patient specific transthoracic echocardiography (TTE) and right heart catheterization (RHC) measures was used to identify key parameters representing cardiovascular hemodynamics. Thirty-one patient records (10 HFrEF, 21 HFpEF) were obtained from the Cardiovascular Health Improvement Project (CHIP) database at the University of Michigan. Model simulations were tuned to match RHC and TTE pressure, volume and cardiac output measures in each patient with average error between data and model of 4.87 ± 2%. The underlying physiological model parameters were then plotted against model-based norms and compared between the HFrEF and HFpEF group. Our results confirm that the main mechanistic parameter driving HFrEF is reduced left ventricular contractility, while for HFpEF a much wider underlying phenotype is presented. Conducting principal component analysis (PCA),k-means, and hierarchical clustering on the optimized model parameters, but not on clinical measures, shows a distinct group of HFpEF patients sharing characteristics with the HFrEF cohort, a second group that is distinct as HFpEF and a group that exhibits characteristics of both. Significant differences are observed (p-value<.001) in left ventricular active contractility and left ventricular relaxation, when comparing HFpEF patients to those grouped as similar to HFrEF. These results suggest that cardiovascular system modeling of standard clinical data is able to phenotype and group HFpEF as different subdiagnoses, possibly elucidating patient-specific treatment strategies.
Large scale genomic rearrangements in selectedArabidopsis thalianaT-DNA lines are caused by T-DNA insertion mutagenesis
Authors: Pucker Boas , Kleinbölting Nils , Weisshaar Bernd 
Published: March 2021

AbstractBackgroundExperimental proof of gene function assignments in plants is based on mutant analyses. T-DNA insertion lines provided an invaluable resource of mutants and enabled systematic reverse genetics-based investigation of the functions ofArabidopsis thalianagenes during the last decades.ResultsWe sequenced the genomes of 14A. thalianaGABI-Kat T-DNA insertion lines, which eluded flanking sequence tag-based attempts to characterize their insertion loci, with Oxford Nanopore Technologies (ONT) long reads. Complex T-DNA insertions were resolved and 11 previously unknown T-DNA loci identified, resulting in about 2 T-DNA insertions per line and suggesting that this number was previously underestimated. T-DNA mutagenesis caused fusions of chromosomes along with compensating translocations to keep the gene set complete throughout meiosis. Also, an inverted duplication of 800 kbp was detected. About 10% of GABI-Kat lines might be affected by chromosomal rearrangements, some of which do not involve T-DNA. Local assembly of selected reads was shown to be a computationally effective method to resolve the structure of T-DNA insertion loci. We developed an automated workflow to support investigation of long read data from T-DNA insertion lines. All steps from DNA extraction to assembly of T-DNA loci can be completed within days.ConclusionLong read sequencing was demonstrated to be an effective way to resolve complex T-DNA insertions and chromosome fusions. Many T-DNA insertions comprise not just a single T-DNA, but complex arrays of multiple T-DNAs. It is becoming obvious that T-DNA insertion alleles must be characterized by exact identification of both T-DNA::genome junctions to generate clear genotype-to-phenotype relations.
Proteomic analysis identifies novel binding partners of BAP1
Authors: Baas Roy , van der Wal Fenna J. , Bleijerveld Onno B. , van Attikum Haico , Sixma Titia K. 
Published: March 2021

AbstractBRCA1-associated protein 1 (BAP1) is a tumor suppressor and its loss can result in mesothelioma, uveal and cutaneous melanoma, clear cell renal cell carcinoma and bladder cancer. BAP1 is a deubiquitinating enzyme of the UCH class that has been implicated in various cellular processes like cell growth, cell cycle progression, ferroptosis and ER metabolic stress response. ASXL proteins activate BAP1 by forming the polycomb repressive deubiquitinase (PR-DUB) complex which acts on H2AK119ub1. Besides the ASXL proteins, BAP1 is known to interact with an established set of additional proteins.Here, we identify novel BAP1 interacting proteins in the cytoplasm by expressing GFP-tagged BAP1 in an endogenous BAP1 deficient cell line using affinity purification followed by mass spectrometry (AP-MS) analysis. Among these novel interacting proteins are Histone acetyltransferase 1 (HAT1) and all subunits of the heptameric coat protein complex I (COPI) that is involved in vesicle formation and protein cargo binding and sorting. We validate that the HAT1 and COPI interactions occur at endogenous levels but find that this interaction with COPI is not mediated through the C-terminal KxKxx cargo sorting signals of the COPI complex.
Mechanistic insights into the success of xenobiotic degraders resolved from metagenomes of microbial enrichment cultures
Authors: Li Junhui , Jia Chongjian , Lu Qihong , Hungate Bruce A. , Dijkstra Paul , Wang Shanquan , Wu Cuiyu , Chen Shaohua , Li Deqiang , Shim Hojae 
Published: March 2021

AbstractEven though microbial communities can be more effective at degrading xenobiotics than cultured micro-organisms, yet little is known about the microbial strategies that underpin xenobiotic biodegradation by microbial communities. Here, we employ metagenomic community sequencing to explore the mechanisms that drive the development of 49 xenobiotic-degrading microbial communities, which were enriched from 7 contaminated soils or sediments with a range of xenobiotic compounds. We show that multiple microbial strategies likely drive the development of xenobiotic degrading communities, notably (i) presence of genes encoding catabolic enzymes to degrade xenobiotics; (ii) presence of genes encoding efflux pumps; (iii) auxiliary catabolic genes on plasmids; and (iv) positive interactions dominate microbial communities with efficient degradation. Overall, the integrated analyses of microbial ecological strategies advance our understanding of microbial processes driving the biodegradation of xenobiotics and promote the design of bioremediation systems.
Comparative evaluation of plasma protein purification and 2-D gel electrophoresis protocols for analysis of HIV-1 infected human plasma proteins
Authors: Barik Sushanta Kumar , Varshney Deepika , Mohanty Keshar Kunja , Bisht Deepa , Patil Shripad A. , Singh Rananjay , Sharma Devesh , Tripathy SrikanthPrasad , Tandon Rekha , Singh Tej Pal , Jena Srikanta 
Published: March 2021

AbstractPurification of proteins from human plasma is a herculean task to perform 2-D gel electrophoresis. Human plasma contains nearly 70% albumin and globulin. The removal of such high abundance high molecular weight proteins is very difficult before performing 2-D gel electrophoresis. It becomes more difficult when we intent to investigate in infectious diseases like HIV/AIDS. We tried to the best of our efforts adopting various organic and non-organic based protocols based on various published papers. After failure of these protocols in results of 2-D gel-electrophoresis Aurum serum mini kit (Bio-Rad, USA) was adopted for plasma protein purification for performing 2-D gel electrophoresis. The low-abundance proteins were better resolved by 10% SDS-PAGE in 2-D gel-electrophoresis. Then,we extended the MALDI-TOF/TOF analysis of low-abundance proteins in human plasma by adopting the Aurum serum mini kit (Bio-Rad, USA) for 2-D gel electrophoresis. Thus, we concluded that, depletion of high abundant proteins like albumin and globulin, the use of the Aurum serum mini kit (Bio-Rad, USA) is the protocol of choice to perform the 2-D gel electrophoresis of HIV-1 infected human plasma.
The enpp4 ectonucleotidase regulates kidney patterning signalling networks inXenopusembryos
Authors: Massé Karine , Bhamra Surinder , Paroissin Christian , Maneta-Peyret Lilly , Boué-Grabot Eric , Jones Elizabeth A. 
Published: March 2021

AbstractThe enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation inXenopus.Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for expression of the pronephric markers and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and surprising non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.
Mutation load decreases with haplotype age in wild Soay sheep
Authors: Stoffel M.A. , Johnston S.E. , Pilkington J.G. , Pemberton J.M 
Published: March 2021

AbstractRuns of homozygosity (ROH) are pervasive in diploid genomes and expose the effects of deleterious recessive mutations, but how exactly these regions contribute to variation in fitness remains unclear. Here, we combined empirical analyses and simulations to explore the deleterious effects of ROH with varying genetic map lengths in wild Soay sheep. Using a long-term dataset of 4,592 individuals genotyped at 417K SNPs, we found that inbreeding depression increases with ROH length. A 1% genomic increase in long ROH (>12.5cM) reduced the odds of first-year survival by 12%, compared to only 7% for medium ROH (1.56-12.5cM), while short ROH (<1.56cM) had no effect on survival. We show by forward genetic simulations that this is predicted: compared with shorter ROH, long ROH will have higher densities of deleterious alleles, with larger average effects on fitness and lower population frequencies. Taken together, our results are consistent with the idea that the mutation load decreases in older haplotypes underlying shorter ROH, where purifying selection has had more time to purge deleterious mutations. Finally, our study demonstrates that strong inbreeding depression can persist despite ongoing purging in a historically small population.
Identification and predictability of soil quality factors and indicators from conventional soil and vegetation classifications
Authors: Simfukwe Paul , Hill Paul W. , Emmett Bridget A. , Jones Davey L. 
Published: March 2021

ABSTRACTGenerally, the physical, chemical and biological attributes of a soil combined with abiotic factors (e.g. climate and topography) drive pedogenesis. However, biological indicators of soil quality play no direct role in traditional soil classification and surveys. To support their inclusion in classification schemes, previous studies have shown that soil type is a key factor determining microbial community composition in arable soils. This suggests that soil type could be used as proxy for soil biological function and vice versa. In this study we assessed the relationship between soil biological indicators with either vegetation cover or soil type. A wide range of soil attributes were measured on soils from across the UK to investigate whether; (1) appropriate soil quality factors (SQFs) and indicators (SQIs) can be identified, (2) soil classification can predict SQIs; (3) which soil quality indicators were more effectively predicted by soil types, and (4) to what extent do soil types and/ or aggregate vegetation classes (AVCs) act as major regulators of SQIs. Factor analysis was used to group 20 soil attributes into six SQFs namely;Soil organic matter,Organic matter humification,Soluble nitrogen,Microbial biomass,Reduced nitrogenandSoil humification index. Of these,Soil organic matterwas identified as the most important SQF in the discrimination of both soil types and AVCs. Among the measured soil attributes constituting theSoil organic matterfactor were, microbial quotient and bulk density were the most important attributes for the discrimination of both individual soil types and AVCs. TheSoil organic matterfactor discriminated three soil type groupings and four aggregate vegetation class groupings. Only the Peat soil and Heath and bog AVC were distinctly discriminated from other groups. All other groups overlapped with one another, making it practically impossible to define reference values for each soil type or AVC. We conclude that conventionally classified soil types cannot predict the SQIs (or SQFs), but can be used in conjunction with the conventional soil classifications to characterise the soil types. The two-way ANOVA showed that the AVCs were a better regulator of the SQIs than the soil types and that they (AVCs) presented a significant effect on the soil type differences in the measured soil attributes.
Scoping review of the applications of peptide microarrays on the fight against human infections
Authors: Vengesai Arthur , Kasambala Maritha , Mutandadzi Hamlet , Mduluza-Jokonya Tariro L. , Mduluza Takafira , Naicker Thajasvarie 
Published: March 2021

AbstractIntroductionThis scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis.MethodsElectronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.ResultsEighty-six articles from 100 studies were included in the final data charting process. The majority (93%) of the articles were published during 2010–2020 and were mostly from Europe (44%) and North America (34 %). The findings were from the investigation of viral (44%), bacterial (30%), parasitic (25%) and fungal (2%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (78%) were related to mapping B-cell linear epitopes, 10% were on diagnostics, 9% reported on immunosignature characterisation and 6% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling.ConclusionThe most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.
NuA4 and SAGA acetyltransferase complexes cooperate for repair of DNA breaks by homologous recombination
Authors: Cheng Xue , Côté Valérie , Côté Jacques 
Published: March 2021

ABSTRACTChromatin modifying complexes play important yet not fully defined roles in DNA repair processes. The essential NuA4 histone acetyltransferase (HAT) complex is recruited to double-strand break (DSB) sites and spreads along with DNA end resection. As predicted, NuA4 acetylates surrounding nucleosomes upon DSB induction and defects in its activity correlate with altered DNA end resection and Rad51 recombinase recruitment. Importantly, we show that NuA4 is also recruited to the donor sequence during recombination along with increased H4 acetylation, indicating a direct role during strand invasion/D-loop formation after resection. We found that NuA4 cooperates locally with another HAT, the SAGA complex, during DSB repair as their combined action is essential for DNA end resection to occur. This cooperation of NuA4 and SAGA is required for recruitment of ATP-dependent chromatin remodelers, targeted acetylation of repair factors and homologous recombination. Our work reveals a multifaceted and conserved cooperation mechanism between acetyltransferase complexes to allow repair of DNA breaks by homologous recombination.Key Points-NuA4-dependent acetylation modulates nucleosome dynamics to assist DNA end resection and strand invasion during homologous recombination.-Combined recruitment and local action of NuA4 and SAGA acetyltransferase complexes is essential for DNA end resection.-Cooperation between NuA4 and SAGA acetyltransferases is required for homologous recombination in eukaryotes.
Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition
Authors: Kabir Mamun , Alam Masud , Nayak Uma , Arju Tuhinur , Hossain Biplob , Tarannum Rubaiya , Khatun Amena , White Jennifer A. , Ma Jennie Z. , Haque Rashidul , Petri William A. , Gilchrist Carol A. 
Published: March 2021

AbstractWe conducted a longitudinal study of cryptosporidiosis from birth to three years of age in an urban slum of Dhaka Bangladesh. Fecal DNA was extracted from monthly surveillance samples and diarrheal stool samples collected from 392 infants from birth to three years. A pan-Cryptosporidium qPCR assay was used to identify sub-clinical and symptomatic cryptosporidiosis. Anthropometric measurements were collected quarterly to assess child nutritional status. 31% (121/392) of children experienced a single and 57% (222/392) multiple infections withCryptosporidium. Repeat infections had a lower burden of parasites in the stool (Cq slope = −1.85; p<0.0001) and were more likely to be sub-clinical (Chi square test for trend; p=0.01). Repeat infections were associated with the development of growth faltering (Pearson correlation = −0.18; p=0.0004). High levels of fecal IgA antibodies against theCryptosporidiumCp23 sporozoite protein at one year of life were associated with a delay in reinfection and amelioration of growth faltering through three years of life (HAZ IgA high responders −1.323 ± 0.932 versus HAZ −1.731 ± 0.984 p=0.0001). We concluded that nonsterile immunity to cryptosporidiosis in young children was associated with high levels of mucosal IgA anti-Cp23 and protection from diarrhea and growth faltering.Authors SummaryCryptosporidiumis one of the top causes of diarrhea and growth faltering in Bangladesh infants. We discovered that a prior infection resulted in incomplete immunity that protected from diarrhea and growth faltering but not infection and was associated with mucosal IgA against a sporozoite surface protein Cp23. The most important implication of these findings is that a cryptosporidiosis vaccine may not need to achieve complete protection from infection to have a beneficial impact on child health.
Constrained standardization of count data from massive parallel sequencing
Authors: Vanhoutven Joris , Cuypers Bart , Meysman Pieter , Hooyberghs Jef , Laukens Kris , Valkenborg Dirk 
Published: March 2021

AbstractIn high-throughput omics disciplines like transcriptomics, researchers face a need to assess the quality of an experiment prior to an in-depth statistical analysis. To efficiently analyze such voluminous collections of data, researchers need triage methods that are both quick and easy to use. Such a normalization method for relative quantitation, CONSTANd, was recently introduced for isobarically-labeled mass spectra in proteomics. It transforms the data matrix of abundances through an iterative, convergent process enforcing three constraints: (I) identical column sums; (II) each row sum is fixed (across matrices) and (III) identical to all other row sums. In this study, we investigate whether CONSTANd is suitable for count data from massively parallel sequencing, by qualitatively comparing its results to those of DESeq2. Further, we propose an adjustment of the method so that it may be applied to identically balanced but differently sized experiments for joint analysis. We find that CONSTANd can process large data sets with about 2 million count records in less than a second whilst removing unwanted systematic bias and thus quickly uncovering the underlying biological structure when combined with a PCA plot or hierarchical clustering. Moreover, it allows joint analysis of data sets obtained from different batches, with different protocols and from different labs but without exploiting information from the experimental setup other than the delineation of samples into identically processed sets (IPSs). CONSTANd’s simplicity and applicability to proteomics as well as transcriptomics data make it an interesting candidate for integration in multi-omics workflows.