bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast
Authors: Klim Joanna , Zielenkiewicz Urszula , Skoneczny Marek , Skoneczna Adrianna , Kurlandzka Anna , Kaczanowski Szymon 
Published: May 2021

Abstract
Background
The impact of genetic interaction networks on evolution is a fundamental issue. Previous studies have demonstrated that the topology of the network is determined by the properties of the cellular machinery. Functionally related genes frequently interact with one another, and they establish modules, e.g., modules of protein complexes and biochemical pathways. In this study, we experimentally tested the hypothesis that compensatory evolutionary modifications, such as mutations and transcriptional changes, occur frequently in genes from perturbed modules of interacting genes.

Results
Using Saccharomyces cerevisiae haploid deletion mutants as a model, we investigated two modules lacking COG7 or NUP133, which are evolutionarily conserved genes with many interactions. We performed laboratory evolution experiments with these strains in two genetic backgrounds (with or without additional deletion of MSH2), subjecting them to continuous culture in a non-limiting minimal medium. Next, the evolved yeast populations were characterized through whole-genome sequencing and transcriptome analyses. No obvious compensatory changes resulting from inactivation of genes already included in modules were identified. The supposedly compensatory inactivation of genes in the evolved strains was only rarely observed to be in accordance with the established fitness effect of the genetic interaction network. In fact, a substantial majority of the gene inactivations were predicted to be neutral in the experimental conditions used to determine the interaction network. Similarly, transcriptome changes during continuous culture mostly signified adaptation to growth conditions rather than compensation of the absence of the COG7, NUP133 or MSH2 genes. However, we noticed that for genes whose inactivation was deleterious an upregulation of transcription was more common than downregulation.

Conclusions
Our findings demonstrate that the genetic interactions and the modular structure of the network described by others have very limited effects on the evolutionary trajectory following gene deletion of module elements in our experimental conditions and has no significant impact on short-term compensatory evolution. However, we observed likely compensatory evolution in functionally related (albeit non-interacting) genes.
Genetic analysis of three maize husk traits by QTL mapping in a maize-teosinte population
Authors: Zhang Xiaolei , Lu Ming , Xia Aiai , Xu Tao , Cui Zhenhai , Zhang Ruiying , Liu Wenguo , He Yan 
Published: May 2021

Abstract
Background
The maize husk consists of numerous leafy layers and plays vital roles in protecting the ear from pathogen infection and dehydration. Teosinte, the wild ancestor of maize, has about three layers of small husk outer covering the ear. Although several quantitative trait loci (QTL) underlying husk morphology variation have been reported, the genetic basis of husk traits between teosinte and maize remains unclear.

Results
A linkage population including 191 BC2F8 inbred lines generated from the maize line Mo17 and the teosinte line X26–4 was used to identify QTL associated with three husk traits: i.e., husk length (HL), husk width (HW) and the number of husk layers (HN). The best linear unbiased predictor (BLUP) depicted wide phenotypic variation and high heritability of all three traits. The HL exhibited greater correlation with HW than HN. A total of 4 QTLs were identified including 1, 1, 2, which are associated with HL, HW and HN, respectively. The proportion of phenotypic variation explained by these QTLs was 9.6, 8.9 and 8.1% for HL, HN and HW, respectively.

Conclusions
The QTLs identified in this study will pave a path to explore candidate genes regulating husk growth and development, and benefit the molecular breeding program based on molecular marker-assisted selection to cultivate maize varieties with an ideal husk morphology.
Clinical indications of premenstrual disorders and subsequent risk of injury: a population-based cohort study in Sweden
Authors: Yang Qian , Sjölander Arvid , Li Yuchen , Viktorin Alexander , Bertone-Johnson Elizabeth R. , Ye Weimin , Fang Fang , Valdimarsdóttir Unnur A. , Lu Donghao 
Published: May 2021

Abstract
Background
Premenstrual disorders, including premenstrual syndrome and premenstrual dysphoric disorder, are suggested to be correlated with suicidal behavior and accidents in cross-sectional and retrospective studies. However, prospective data are still lacking.

Methods
We performed a population-based cohort study including 1,472,379 Swedish women of reproductive age who were followed from 2001 to 2012. Within the cohort, we also performed a sibling analysis where we compared the rates of injury between full sisters. By linking to the Patient and the Prescribed Drug Registers, we identified 18,628 women with any clinical indications for premenstrual disorders in the cohort (population analysis) and 7674 women in the sibling analysis. Any injury, primarily suicidal behavior (completed suicide and suicide attempt) or accidents (e.g., fall and transportation accidents), was identified through the Patient and Causes of Death Registers as the primary outcome. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of these outcomes among women with premenstrual disorders in both population and sibling analyses using multivariable Cox proportional hazards regression.

Results
During a maximal follow-up of 12 years (mean 9.55 years), we identified 2390 women with premenstrual disorders with any injury; 216 through suicidal behavior and 2191 through accidents. Compared to women without premenstrual disorders, women with premenstrual disorders were at increased risk of any injury (HR 1.37, 95% CI 1.31–1.42), particularly suicidal behavior (HR 2.26, 95% CI 1.97–2.59) and accidents (HR 1.32, 95% CI 1.27–1.38). Such associations somewhat attenuated yet remained significant in the sibling analysis (HRs: 1.31 for any injury, 1.86 for suicidal behavior, and 1.29 for accidents). Additional adjustment for psychiatric comorbidities minimally altered the associations with any injury and accidents in both population and sibling analyses, whereas the association with suicidal behavior was considerably attenuated to non-significance in the sibling analysis. Such risks were particularly strong within 2 years after receiving the diagnosis of premenstrual disorders and were evident among women with premenstrual disorders with and without psychiatric comorbidities.

Conclusions
Our findings suggest that women with a clinical indication of premenstrual disorders are at increased subsequent risk of injury, particularly accidents within the first 2 years after diagnosis.
Effects of increasing intake of soybean oil on synthesis of testosterone in Leydig cells
Authors: Su Yu , Tian Zhenhua , Qi Xiangyu , Luo Dandan , Liu Luna , Liu Shuang , Zheng Dongmei , Wei Fang , He Zhao , Guan Qingbo 
Published: May 2021

Abstract
Background
Soybean oil is a very common edible oil in daily life. With the changes in the dietary composition, the intake of soybean oil increased. However, the effects of dietary intake of soybean oil on testosterone production are still unclear.

Methods
In order to study the effects of increasing intake of soybean oil on the synthesis of testosterone in Leydig cells, we fed male C57BL/6 mice on the diet which added 20% soybean salad oil (SOY group). We detected the hormone levels by enzyme-linked immunosorbent assay (ELISA) kits and serum fatty acid composition by gas chromatography, and analyzed the expression of steroidogenic enzymes by Real-Time PCR or immunoblotting analysis.

Results
After the 16-week feeding period, serum linoleic acid (LA) and α-linolenic acid (ALA) significantly increased and serum palmitic acid (PA) significantly decreased in SOY group mice. Compared to the normal diet (ND group), increasing intake of soybean oil raised the luteinizing hormone (LH) levels and up-regulated luteinizing hormone/chorionic gonadotropin receptor (LHCGR), steroidogenic acute regulatory protein (StAR) and cytochrome P450 family 11 subfamily A member I (CYP11A1). Testosterone levels in SOY group were higher than that in the ND group, and significantly difference showed.

Conclusions
Increasing intake of soybean oil could raise the serum LA and ALA levels and decrease serum PA levels. This could activate the LH/LHCGR pathway and improve the function of steroid synthesis in Leydig cells, and finally lead to the elevated testosterone levels.
Targeted sequencing of NOTCH signaling pathway genes and association analysis of variants correlated with mandibular prognathism
Authors: Han Xianzhuo , Xiong Xueyan , Shi Xiujuan , Chen Fengshan , Li Yongming 
Published: May 2021

Abstract
Introduction
The purpose of this study was to systematically identify variants in NOTCH signaling pathway genes that correlate with mandibular prognathism (MP) in the general Chinese population.

Methods
Targeted sequencing of NOTCH signaling pathway genes was conducted in 199 MP individuals and 197 class I malocclusion control individuals. The associations of common and rare variants with MP, cephalometric parameters, and continuous cephalometric phenotypes were analyzed by principal component (PC) analysis. The associations between rare variants and MP were tested for each gene.

Results
Six SNPs, including rs415929, rs520688, and rs423023 in an exonic region of NOTCH4; rs1044006 in an exonic region of NOTCH3; rs1051415 in an exonic region of JAG1; and rs75236173 in the 3′-untranslated region (3′-UTR) of NUMB were associated with MP (P < 0.05). One common variant, rs1051415, in an exonic region of JAG1 was significantly related to PC1 (P  = 3.608 × 10− 4), which explained 24.3% of the overall phenotypic variation observed and corresponded to the sagittal mandibular position towards the maxilla, ranging from a posterior positioned mandible to an anterior positioned mandible. Additionally, 41 other variants were associated with PC1–5 (P  <  0.05). With respect to rare variant analysis, variants within the EP300, NCOR2, and PSEN2 gene showed an association with MP (t   < 0 .05).

Conclusions
An association between NOTCH signaling pathway genes and MP has been identified.
The changing alcohol drinking patterns among older adults show that women are closing the gender gap in more frequent drinking: the Tromsø study, 1994–2016
Authors: Stelander Line Tegner , Høye Anne , Bramness Jørgen G. , Selbæk Geir , Lunde Linn-Heidi , Wynn Rolf , Grønli Ole Kristian 
Published: May 2021

Abstract
Background
As the population of older adults continues to grow, changes in alcohol consumption are important to monitor because an increase may have public health consequences. Rates of alcohol use vary with geographical location. The aim of this study was to examine trends in alcohol consumption among older adults in a geographically defined area in Norway, especially changing sex differences in drinking patterns over a 22-year period.

Methods
Repeated cross-sectional survey (in 1994–95, 2007–08, and 2015–16) of a general population of older adults. Eligible for this study were 20,939 participants (aged 60–99 years). The data were analysed using generalized estimating equations, stratified by age and sex. Alcohol consumption and drinking patterns were assessed, using an adaptation of the AUDIT-C.

Results
Between 1994 and 2016, there has been a significant increase in the proportion of current drinkers among older adults. Furthermore, the probability of frequent drinking (alcohol consumption at least twice weekly) increased significantly between 1994 and 2016, particularly among older women; OR 8.02 (CI 5.97–10.79) and OR 5.87 (CI 4.00–8.63) in the age groups 60–69 and 70+ respectively for women, and OR 4.13 (CI 3.42–4.99) and OR 3.10 (CI 2.41–3.99), in the age groups 60–69 and 70+ respectively for men. The majority of older adults drank small amounts of alcohol on typical drinking days, but there was an increasing probability of drinking three drinks or more on each occasion over the study period, except among women aged 70+ years.

Conclusions
Among older adults in Norway, alcohol consumption in terms of frequency and quantity on typical drinking days has increased considerably from 1996 to 2016. This change is in the opposite direction of what has been reported among younger adults. The gap between women and men in frequent drinking has been markedly narrowed, which indicate that women’s drinking patterns are approaching those of men. This may involve a need to change alcohol policy in Norway to more targeted interventions aimed at older people.
TET2 and DNMT3A mutations and exceptional response to 4′-thio-2′-deoxycytidine in human solid tumor models
Authors: Yang Sherry X. , Hollingshead Melinda , Rubinstein Larry , Nguyen Dat , Larenjeira Angelo B. A. , Kinders Robert J. , Difilippantonio Michael , Doroshow James H. 
Published: May 2021

Abstract
Background
Challenges remain on the selection of patients who potentially respond to a class of drugs that target epigenetics for cancer treatment. This study aims to investigate TET2/DNMT3A mutations and antitumor activity of a novel epigenetic agent in multiple human cancer cell lines and animal models.

Methods
Seventeen cancer cell lines and multiple xenograft models bearing representative human solid tumors were subjected to 4′-thio-2′-deoxycytidine (T-dCyd) or control treatment. Gene mutations in cell lines were examined by whole exome and/or Sanger sequencing. Specific gene expression was measured in cells and xenograft tumor samples by Western blotting and immunohistochemistry. TET2/DNMT3A mutation status in 47,571 human tumor samples was analyzed at cBioPortal for Cancer Genomics.

Results
Cell survival was significantly inhibited by T-dCyd in breast BT549, lung NCI-H23, melanoma SKMEL5 and renal ACHN cancer lines harboring deleterious TET2 and nonsynonymous DNMT3A mutations compared to 13 lines without such mutation pattern (P = 0.007). The treatment upregulated p21 and induced cell cycle arrest in NCI-H23 cells, and dramatically inhibited their xenograft tumor growth versus wildtype models. T-dCyd administrations led to a significant p21 increase and near eradication of tumor cells in the double-mutant xenografts by histological evaluation. TET2/DNMT3A was co-mutated in human lung, breast, skin and kidney cancers and frequently in angioimmunoblastic and peripheral T cell lymphomas and several types of leukemia.

Conclusions
Cell and animal models with concurrent mutations in TET2 and DNMT3A were sensitive to T-dCyd treatment. The mutations were detectable in human solid tumors and frequently occur in some hematological malignancies.
Retrieving and processing agro-meteorological data from API-client sources using R software
Authors: Correndo Adrian A. , Moro Rosso Luiz H. , Ciampitti Ignacio A. 
Published: May 2021

Abstract
Objectives
The main purpose of this publication is to help users (students, researchers, farmers, advisors, etc.) of weather data with agronomic purposes (e.g. crop yield forecast) to retrieve and process gridded weather data from different Application Programming Interfaces (API client) sources using R software.

Data description
This publication consists of a code-tutorial developed in R that is part of the data-curation process from numerous research projects carried out by the Ciampitti’s Lab, Department of Agronomy, Kansas State University. We make use of three weather databases for which specific libraries were developed in R language: (i) DAYMET (Thornton et al. in https://daymet.ornl.gov/, 2019; https://github.com/bluegreen-labs/daymetr), (ii) NASA-POWER (Sparks in J Open Source Softw 3:1035, 2018; https://github.com/ropensci/nasapower), and (iii) Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS) (Funk et al. in Sci Data 2:150066, 2015; https://github.com/ropensci/chirps). The databases offer different weather variables, and vary in terms of spatio-temporal coverage and resolution. The tutorial shows and explain how to retrieve weather data from multiple locations at once using latitude and longitude coordinates. Additionally, it offers the possibility to create relevant variables and summaries that are of agronomic interest such as Shannon Diversity Index (SDI) of precipitation, abundant and well distributed rainfall (AWDR), growing degree days (GDD), crop heat units (CHU), extreme precipitation (EPE) and temperature events (ETE), reference evapotranspiration (ET0), among others.
Benchmarks for interpretation of QSAR models
Authors: Matveieva Mariia , Polishchuk Pavel 
Published: May 2021

AbstractInterpretation of QSAR models is useful to understand the complex nature of biological or physicochemical processes, guide structural optimization or perform knowledge-based validation of QSAR models. Highly predictive models are usually complex and their interpretation is non-trivial. This is particularly true for modern neural networks. Various approaches to interpretation of these models exist. However, it is difficult to evaluate and compare performance and applicability of these ever-emerging methods. Herein, we developed several benchmark data sets with end-points determined by pre-defined patterns. These data sets are purposed for evaluation of the ability of interpretation approaches to retrieve these patterns. They represent tasks with different complexity levels: from simple atom-based additive properties to pharmacophore hypothesis. We proposed several quantitative metrics of interpretation performance. Applicability of benchmarks and metrics was demonstrated on a set of conventional models and end-to-end graph convolutional neural networks, interpreted by the previously suggested universal ML-agnostic approach for structural interpretation. We anticipate these benchmarks to be useful in evaluation of new interpretation approaches and investigation of decision making of complex “black box” models.
Cell subtypes and immune dysfunction in peritoneal fluid of endometriosis revealed by single-cell RNA-sequencing
Authors: Zou Gen , Wang Jianzhang , Xu Xinxin , Xu Ping , Zhu Libo , Yu Qin , Peng Yangying , Guo Xinyue , Li Tiantian , Zhang Xinmei 
Published: May 2021

Abstract
Background
Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells.

Results
High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis.

Conclusion
TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.
New multiplicity of positive solutions for some class of nonlocal problems
Authors: Shi Zhigao , Qian Xiaotao 
Published: May 2021

AbstractIn this paper, we study the following nonlocal problem: $$ \textstyle\begin{cases} - (a-b \int _{\Omega } \vert \nabla u \vert ^{2}\,dx ) \Delta u= \lambda \vert u \vert ^{q-2}u, & x\in \Omega , \\ u=0, & x\in \partial \Omega , \end{cases} $$

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Pre-digest of unprotected DNA by Benzonase improves the representation of living skin bacteria and efficiently depletes host DNA
Authors: Amar Yacine , Lagkouvardos Ilias , Silva Rafaela L. , Ishola Oluwaseun Ayodeji , Foesel Bärbel U. , Kublik Susanne , Schöler Anne , Niedermeier Sebastian , Bleuel Rachela , Zink Alexander , Neuhaus Klaus , Schloter Michael , Biedermann Tilo , Köberle Martin 
Published: May 2021

Abstract
Background
The identification of microbiota based on next-generation sequencing (NGS) of extracted DNA has drastically improved our understanding of the role of microbial communities in health and disease. However, DNA-based microbiome analysis cannot per se differentiate between living and dead microorganisms. In environments such as the skin, host defense mechanisms including antimicrobial peptides and low cutaneous pH result in a high microbial turnover, likely resulting in high numbers of dead cells present and releasing substantial amounts of microbial DNA. NGS analyses may thus lead to inaccurate estimations of microbiome structures and consequently functional capacities.

Results
We investigated in this study the feasibility of a Benzonase-based approach (BDA) to pre-digest unprotected DNA, i.e., of dead microbial cells, as a method to overcome these limitations, thus offering a more accurate assessment of the living microbiome. A skin mock community as well as skin microbiome samples were analyzed using 16S rRNA gene sequencing and metagenomics sequencing after DNA extraction with and without a Benzonase digest to assess bacterial diversity patterns. The BDA method resulted in less reads from dead bacteria both in the skin mock community and skin swabs spiked with either heat-inactivated bacteria or bacterial-free DNA. This approach also efficiently depleted host DNA reads in samples with high human-to-microbial DNA ratios, with no obvious impact on the microbiome profile. We further observed that low biomass samples generate an α-diversity bias when the bacterial load is lower than 105 CFU and that Benzonase digest is not sufficient to overcome this bias.

Conclusions
The BDA approach enables both a better assessment of the living microbiota and depletion of host DNA reads.

Graphical abstract