bluuebunny/crossref_metadata_2025_split huggingface dataset:
IntAct App: a Cytoscape application for molecular interaction network visualization and analysis
Authors: Ragueneau Eliot , Shrivastava Anjali , Morris John H , del-Toro Noemi , Hermjakob Henning , Porras Pablo 
Published: April 2021

AbstractSummaryIntAct App is a Cytoscape 3 application that grants in-depth access to IntAct’s molecular interaction data. It build networks where nodes are interacting molecules (mainly proteins, but also genes, RNA, chemicals…) and edges represent evidence of interaction. Users can query a network by providing its molecules, identified by different fields and optionally include all their interacting partners in the resulting network. The app offers three visualizations: one only displaying interactions, another representing every evidence and the last one emphasizing evidence where mutated versions of proteins were used. Users can also filter networks and click on nodes and edges to access all their related details. Finally, the application supports automation of its main features via Cytoscape commands.Availability and implementationImplementation available at https://apps.cytoscape.org/apps/intactapp, while the source code is available at https://github.com/EBI-IntAct/IntactApp.
Reactome and the Gene Ontology: digital convergence of data resources
Authors: Good Benjamin M , Van Auken Kimberly , Hill David P , Mi Huaiyu , Carbon Seth , Balhoff James P , Albou Laurent-Philippe , Thomas Paul D , Mungall Christopher J , Blake Judith A , D’Eustachio Peter 
Published: April 2021

Abstract

Motivation
Gene Ontology Causal Activity Models (GO-CAMs) assemble individual associations of gene products with cellular components, molecular functions and biological processes into causally linked activity flow models. Pathway databases such as the Reactome Knowledgebase create detailed molecular process descriptions of reactions and assemble them, based on sharing of entities between individual reactions into pathway descriptions.

Results
To convert the rich content of Reactome into GO-CAMs, we have developed a software tool, Pathways2GO, to convert the entire set of normal human Reactome pathways into GO-CAMs. This conversion yields standard GO annotations from Reactome content and supports enhanced quality control for both Reactome and GO, yielding a nearly seamless conversion between these two resources for the bioinformatics community.

Supplementary information
Supplementary data are available at Bioinformatics online.
Analysis of Dynamic Network Reconfiguration in Adults with Attention-Deficit/Hyperactivity Disorder Based Multilayer Network
Authors: Cui Xiaohong , Ding Congli , Wei Jing , Xue Jiayue , Wang Xiaoyue , Wang Bin , Xiang Jie 
Published: April 2021

Abstract
Attention-deficit/hyperactivity disorder (ADHD) has been reported exist abnormal topology structure in the brain network. However, these studies often treated the brain as a static monolithic structure, and dynamic characteristics were ignored. Here, we investigated how the dynamic network reconfiguration in ADHD patients differs from that in healthy people. Specifically, we acquired resting-state functional magnetic resonance imaging data from a public dataset including 40 ADHD patients and 50 healthy people. A novel model of a “time-varying multilayer network” and metrics of recruitment and integration were applied to describe group differences. The results showed that the integration scores of ADHD patients were significantly lower than those of controls at every level. The recruitment scores were lower than healthy people except for the whole-brain level. It is worth noting that the subcortical network and the thalamus in ADHD patients exhibited reduced alliance preference both within and between functional networks. In addition, we also found that recruitment and integration coefficients showed a significant correlation with symptom severity in some regions. Our results demonstrate that the capability to communicate within or between some functional networks is impaired in ADHD patients. These evidences provide a new opportunity for studying the characteristics of ADHD brain networks.
Focal Subcortical White Matter Lesions Disrupt Resting State Cortical Interhemispheric Functional Connectivity in Mice
Authors: Aykan Sanem A , Xie Hongyu , Lai James Han , Zheng Yi , Chung David Y , Kura Sreekanth , Anzabi Maryam , Sugimoto Kazutaka , McAllister Lauren M , Yaseen M Abbas , Boas David A , Whalen Michael J , Sakadzic Sava , Ayata Cenk 
Published: April 2021

AbstractThe corpus callosum is the largest white matter tract and critical for interhemispheric connectivity. Unfortunately, neurocognitive deficits after experimental white matter lesions are subtle and variable, limiting their translational utility. We examined resting state functional connectivity (RSFC) as a surrogate after a focal lesion in the lateral corpus callosum induced by stereotaxic injection of L-NIO in mice. RSFC was performed via optical intrinsic signal imaging through intact skull before and on days 1 and 14 after injection, using interhemispheric homotopic and seed-based temporal correlation maps. We measured the lesion volumes at 1 month in the same cohort. L-NIO induced focal lesions in the corpus callosum. Interhemispheric homotopic connectivity decreased by up to 50% 24 h after L-NIO, partially sparing the visual cortex. All seeds showed loss of connectivity to the contralateral hemisphere. Moreover, ipsilesional motor and visual cortices lost connectivity within the same hemisphere. Sham-operated mice did not show any lesion or connectivity changes. RSFC imaging reliably detects acute disruption of long interhemispheric and intrahemispheric connectivity after a corpus callosum lesion in mice. This noninvasive method can be a functional surrogate to complement neurocognitive testing in both therapeutic and recovery studies after white matter injury.
The results of aortic arch replacement using antegrade cerebral perfusion in haemodialysis patients: analysis of the Japan cardiovascular surgery database
Authors: Saito Yoshiaki , Yamamoto Hiroyuki , Fukuda Ikuo , Miyata Hiroaki , Minakawa Masahito , Motomura Noboru 
Published: April 2021

Abstract

OBJECTIVES
There have been limited data available regarding aortic arch replacement in dialysis patients. The purpose of this study was to examine real-world data and to determine the impact of preoperative dialysis status and other risks on surgical aortic arch replacement using the Japan Cardiovascular Surgery Database.

METHODS
A total of 5044 patients who underwent elective, isolated aortic arch replacement using antegrade cerebral perfusion during 2014–2017 were eligible for the study. Of these, 89 patients received haemodialysis preoperatively. The patients were divided into 6 groups according to their preoperative estimated glomerular filtration rate and dialysis status for comparison. Preoperative and postoperative data were examined using a multivariable regression model.

RESULTS
The overall surgical mortality rates of non-Chronic Kidney Disease (CKD) (estimated glomerular filtration rate &gt;60 ml/min/1.73 m2), stage 3A, stage 3B, stage 4, stage 5 CKD and dialysis patients were 2.6%, 3.1%, 6.8%, 11.6%, 16.7% and 13.5%, respectively. After risk adjustment, dialysis was shown to be strongly associated with surgical mortality (odds ratio 4.39 and 95% confidence interval 2.22–8.72) and have a trend to be associated with postoperative stroke (odds ratio 2.02, 95% confidence interval 1.00–4.10, P = 0.051) when compared to the non-CKD group. As predictors of mortality, male sex, peripheral arterial disease, preoperative liver dysfunction and impaired left ventricular function were identified.

CONCLUSIONS
The Japanese nationwide database revealed the outcomes of aortic arch replacement in dialysis patients. Appropriate counselling and an alternative strategy should be considered for such patients with multiple risks for mortality.
When Ethnicity and Gender Align: Classroom Composition, Friendship Segregation, and Collective Identities in European Schools
Authors: Kroneberg Clemens , Kruse Hanno , Wimmer Andreas 
Published: April 2021

AbstractUsing survey data on school classes in four European countries, we study how the social relations and identities of adolescents develop depending on the degree to which ethnic and gender boundaries align with each other. Minority students will have mostly same-ethnic friends, we find, when classmates of different ethnic origins tend to be of the opposite sex as well. Within such local topographies of boundaries, minority students will also end up identifying less as members of the nation. In contrast, majority students are not affected by the alignment of ethnic and gender boundaries, and gender identities of both minorities and majorities are less malleable as well: Neither friendship segregation along gender divides nor the development of gender role attitudes depend on the degree to which gender and ethnic origin align. We argue that gender boundaries and feelings of national belonging among majority students are widely taken for granted and thus less sensitive to attribute alignment at the local level. The article builds a bridge between the literatures on ethnic segregation of friendship networks, adolescent ethnic identities, and gender role attitudes by integrating them into a structuralist framework that identifies the conditions under which the local configuration of boundaries affects social life.
MeSCoT: the tool for quantitative trait simulation through the mechanistic modeling of genes’ regulatory interactions
Authors: Milkevych Viktor , Karaman Emre , Sahana Goutam , Janss Luc , Cai Zexi , Lund Mogens Sandø 
Published: April 2021

Abstract
This work represents a novel mechanistic approach to simulate and study genomic networks with accompanying regulatory interactions and complex mechanisms of quantitative trait formation. The approach implemented in MeSCoT software is conceptually based on the omnigenic genetic model of quantitative (complex) trait, and closely imitates the basic in vivo mechanisms of quantitative trait realization. The software provides a framework to study molecular mechanisms of gene-by-gene and gene-by-environment interactions underlying quantitative trait’s realization and allows detailed mechanistic studies of impact of genetic and phenotypic variance on gene regulation. MeSCoT performs a detailed simulation of genes’ regulatory interactions for variable genomic architectures and generates complete set of transcriptional and translational data together with simulated quantitative trait values. Such data provide opportunities to study, for example, verification of novel statistical methods aiming to integrate intermediate phenotypes together with final phenotype in quantitative genetic analyses or to investigate novel approaches for exploiting gene-by-gene and gene-by-environment interactions.
Simultaneous Estimation of All the Parameters of a Stepwise Mutation Model
Authors: Fu Yun-Xin , Chakraborty Ranajit 
Published: April 2021

Abstract
Minisatellite and microsatellite are short tandemly repetitive sequences dispersed in eukaryotic genomes, many of which are highly polymorphic due to copy number variation of the repeats. Because mutation changes copy numbers of the repeat sequences in a generalized stepwise fashion, stepwise mutation models are widely used for studying the dynamics of these loci. We propose a minimum chi-square (MCS) method for simultaneous estimation of all the parameters in a stepwise mutation model and the ancestral allelic type of a sample. The MCS estimator requires knowing the mean number of alleles of a certain size in a sample, which can be estimated using Monte Carlo samples generated by a coalescent algorithm. The method is applied to samples of seven (CA)n repeat loci from eight human populations and one chimpanzee population. The estimated values of parameters suggest that there is a general tendency for microsatellite alleles to expand in size, because (1) each mutation has a slight tendency to cause size increase and (2) the mean size increase is larger than the mean size decrease for a mutation. Our estimates also suggest that most of these CA-repeat loci evolve according to multistep mutation models rather than single-step mutation models. We also introduced several quantities for measuring the quality of the estimation of ancestral allelic type, and it appears that the majority of the estimated ancestral allelic types are reasonably accurate. Implications of our analysis and potential extensions of the method are discussed.
Locating Regions of Differential Variability in DNA and Protein Sequences
Authors: Tang Hua , Lewontin R C 
Published: April 2021

Abstract
In the comparison of DNA and protein sequences between species or between paralogues or among individuals within a species or population, there is often some indication that different regions of the sequence are divergent or polymorphic to different degrees, indicating differential constraint or diversifying selection operating in different regions of the sequence. The problem is to test statistically whether the observed regional differences in the density of variant sites represent real differences and then to estimate as accurately as possible the location of the differential regions. A method is given for testing and locating regions of differential variation. The method consists of calculating G(xk) = k/n – xk/N, where xk is the position of the kth variant site along the sequence, n is the total number of variant sites, and N is the total sequence length. The estimated region is the longest stretch of adjacent sequence for which G(xk) is monotonically increasing (a hot spot) or decreasing (a cold spot). Critical values of this length for tests of significance are given, a sequential method is developed for locating multiple differential regions, and the power of the method against various alternatives is explored. The method locates the endpoints of hot spots and cold spots of variation with high accuracy.
Role of Exonucleolytic Degradation in Group I Intron Homing in Phage T4
Authors: Huang Yi-Jiun , Parker Monica M , Belfort Marlene 
Published: April 2021

Abstract
Homing of the phage T4 td intron is initiated by the intron-encoded endonuclease I-TevI, which cleaves the intronless allele 23 and 25 nucleotides upstream of the intron insertion site (IS). The distance between the I-TevI cleavage site (CS) and IS implicates endo- and/or exonuclease activities to resect the DNA segment between the IS and CS. Furthermore, 3′ tails must presumably be generated for strand invasion by 5′-3′ exonuclease activity. Three experimental approaches were used to probe for phage nucleases involved in homing: a comparative analysis of in vivo homing levels of nuclease-deficient phage, an in vitro assay of nuclease activity and specificity, and a coconversion analysis of flanking exon markers. It was thereby demonstrated that T4 RNase H, a 5′-3′ exonuclease, T4 DNA exonuclease A (DexA) and the exonuclease activity of T4 DNA polymerase (43Exo), 3′-5′ exonucleases, play a role in intron homing. The absence of these functions impacts not only homing efficiency but also the extent of degradation and flanking marker coconversion. These results underscore the critical importance of the 3′ tail in intron homing, and they provide the first direct evidence of a role for 3′ single-stranded DNA ends as intermediates in T4 recombination. Also, the involvement of RNase H, DexA, and 43Exo in homing provides a clear example of the harnessing of functions variously involved in phage nucleic acid metabolism for intron propagation.
Identification of Ascorbic Acid-Deficient Arabidopsis thaliana Mutants
Authors: Conklin Patricia L , Saracco Scott A , Norris Susan R , Last Robert L 
Published: April 2021

Abstract
Vitamin C (l-ascorbic acid) is a potent antioxidant and cellular reductant present at millimolar concentrations in plants. This small molecule has roles in the reduction of prosthetic metal ions, cell wall expansion, cell division, and in the detoxification of reactive oxygen generated by photosynthesis and adverse environmental conditions. However, unlike in animals, the biosynthesis of ascorbic acid (AsA) in plants is only beginning to be unraveled. The previously described AsA-deficient Arabidopsis mutant vtc1 (vitamin c-1) was recently shown to have a defect in GDP-mannose pyrophosphorylase, providing strong evidence for the recently proposed role of GDP-mannose in AsA biosynthesis. To genetically define other AsA biosynthetic loci, we have used a novel AsA assay to isolate four vtc mutants that define three additional VTC loci. We have also isolated a second mutant allele of VTC1. The four loci represented by the vtc mutant collection have been genetically characterized and mapped onto the Arabidopsis genome. The vtc mutants have differing ozone sensitivities. In addition, two of the mutants, vtc2-1 and vtc2-2, have unusually low levels of AsA in the leaf tissue of mature plants.
Biased Estimation of the Recombination Fraction Using Half-Sib Families and Informative Offspring
Authors: Gomez-Raya L 
Published: April 2021

Abstract
A maximum-likelihood method to estimate the recombination fraction and its sampling variance using informative and noninformative half-sib offspring is derived. Estimates of the recombination fraction are biased up to 20 cM when noninformative offspring are discarded. In certain scenarios, the sampling variance can be increased or reduced up to fivefold due to the bias in estimating the recombination fraction and the LOD score can be reduced up to 5 units when discarding noninformative offspring. Comparison of the estimates of recombination fraction, map distance, and LOD score when constructing a genetic map with 251 two-point linkage analyses and six families of Norwegian cattle was carried out to evaluate the implications of discarding noninformative offspring in practical situations. The average discrepancies in absolute value (average difference when using and neglecting noninformative offspring) were 0.0146, 1.64 cM, and 2.61 for the recombination fraction, map distance, and the LOD score, respectively. A method for simultaneous estimation of allele frequencies in the dam population and a transmission disequilibrium parameter is proposed. This method might account for the bias in estimating allele frequencies in the dam population when the half-sib offspring is selected for production traits.
Theory of Time-Resolved Somatic Complementation and Its Use to Explore the Sporulation Control Network in Physarum polycephalum
Authors: Marwan Wolfgang 
Published: April 2021

Abstract
Mutants of Physarum polycephalum can be complemented by fusion of plasmodial cells followed by cytoplasmic mixing. Complementation between strains carrying different mutational defects in the sporulation control network may depend on the signaling state of the network components. We have previously suggested that time-resolved somatic complementation (TRSC) analysis with such mutants may be used to probe network architecture and dynamics. By computer simulation it is now shown how and under which conditions the regulatory hierarchy of genes can be determined experimentally. A kinetic model of the sporulation control network is developed, which is then used to demonstrate how the mechanisms of TRSC can be understood and simulated at the kinetic level. On the basis of theoretical considerations, experimental parameters that determine whether functional complementation of two mutations will occur are identified. It is also shown how gene dosage-effect relationships can be employed for network analysis. The theoretical framework provided may be used to systematically analyze network structure and dynamics through time-resolved somatic complementation studies. The conclusions drawn are of general relevance in that they do not depend on the validity of the model from which they were derived.
Single-Nucleotide Polymorphisms of the Trypanosoma cruzi MSH2 Gene Support the Existence of Three Phylogenetic Lineages Presenting Differences in Mismatch-Repair Efficiency
Authors: Augusto-Pinto Luiz , Teixeira Santuza M R , Pena Sérgio D J , Machado Carlos Renato 
Published: April 2021

Abstract
We have identified single-nucleotide polymorphisms (SNPs) in the mismatch-repair gene TcMSH2 from Trypanosoma cruzi. Phylogenetic inferences based on the SNPs, confirmed by RFLP analysis of 32 strains, showed three distinct haplogroups, denominated A, B, and C. Haplogroups A and C presented strong identity with the previously described T. cruzi lineages I and II, respectively. A third haplogroup (B) was composed of strains presenting hybrid characteristics. All strains from a haplogroup encoded the same specific protein isoform, called, respectively, TcMHS2a, TcMHS2b, and TcMHS2c. The classification into haplogroups A, B, and C correlated with variation in the efficiency of mismatch repair in these cells. When microsatellite loci of strains representative of each haplogroup were analyzed after being cultured in the presence of hydrogen peroxide, new microsatellite alleles were definitely seen in haplogroups B and C, while no evidence of microsatellite instability was found in haplogroup A. Also, cells from haplogroups B and C were considerably more resistant to cisplatin treatment, a characteristic known to be conferred by deficiency of mismatch repair in eukaryotic cells. Altogether, our data suggest that strains belonging to haplogroups B and C may have decreased mismatch-repair ability when compared with strains assigned to the haplogroup A lineage.
New Genes That Interact With lin-35 Rb to Negatively Regulate the let-60 ras Pathway in Caenorhabditis elegans
Authors: Thomas Jeffrey H , Ceol Craig J , Schwartz Hillel T , Horvitz H Robert 
Published: April 2021

Abstract
Previous studies have shown that a synthetic multivulva phenotype results from mutations in genes that antagonize the ras-mediated intercellular signaling system responsible for vulval induction in Caenorhabditis elegans. Synthetic multivulva mutations define two classes of genes, A and B, and a mutation in a gene of each class is required to produce the multivulva phenotype. The ectopic vulval tissue in multivulva animals is generated by vulval precursor cells that in the wild type do not generate vulval tissue. One of the class B synthetic multivulva genes, lin-35, encodes a protein similar to the retinoblastoma (Rb) protein. In this article, we describe the isolation and characterization of 50 synthetic multivulva mutations, the identification of new components of both the class A and class B lin-35 Rb pathways, and the cloning of lin-52, a class B gene that may have a conserved role in Rb-mediated signaling.
Mechanosensory Inputs Influence Caenorhabditis elegans Pharyngeal Activity via Ivermectin Sensitivity Genes
Authors: Keane John , Avery Leon 
Published: April 2021

Abstract
Mechanical stimulation induces opposite behavioral responses in the adult and dauer pharynx. Tail tap of adults inhibits pharyngeal pumping via a pathway involving the innexin gene unc-7 and components of the glutamatergic pathway encoded by the genes avr-14 and avr-15. Tail tap of dauers stimulates pumping through a mechanism involving Gαo and Gαq. The nematocidal drug ivermectin is believed to kill worms by opening a glutamate-gated chloride channel (AVR-15) on pharyngeal muscle, causing complete pumping inhibition. However, ivermectin can also inhibit pumping in the absence of this channel. We propose that one of the ways ivermectin could prevent pumping, in the absence of the AVR-15 ivermectin-binding channel on pharynx muscle, is to target AVR-14 and AVR-15, which are expressed in the inhibitory pathway linking mechanosensation and pumping activity.