bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE USE OF COMPLEMENTARY PRACTICES BY PATIENTS UNDERGOING MEDICALLY ASSISTED REPRODUCTION: The place of Chinese medicine and related practices
Authors: Serri O. , Meunier A. , Bouet P.E. , El Hachem H. , Liu B. , May-Panloup P. 
Published: July 2024

ABSTRACTPurposeInfertility is associated with different factors, highly intricated but sometimes ill-defined. Despite the significant recent technological and therapeutic advancements, the success rates of assisted reproductive technologies (ART) remain relatively low. In this context several women have recourse to complementary practices (CP), in the hope of improving success rates and lowering the associated strain. These methods, are quite heterogenous, and are yet to be comprehensively analyzed in the literature.The objective of our study was to evaluate, in women consulting at our fertility center, the current interest in these CP and more specifically, the role of Traditional Chinese Medicine (TCM) and associated Mind Body Intervention (MBI).MethodsA prospective monocentric survey study at the fertility center of the Angers University Hospital between January and May 2022.Results150 questionnaires were analyzed. Approximately 50% of women have recourse to CP, in the hope of improving the success rates of ART and reducing the associated stress and fatigue. The main CP used were the ones based on body manipulation, TCM and MBI. The lack of use was mainly linked to a lack of knowledge of these methods, and the vast majority of women would like to receive additional information about CP from the physicians at the center.ConclusionOur study shows a significant interest in CP in reproductive medicine. In view of the benefits of some of these practices, at least on the quality of life of patients, information on their value should be made available to all couples undergoing ART.
Simplifying causal gene identification in GWAS loci
Authors: Schipper Marijn , Ulirsch Jacob , Posthuma Danielle , Ripke Stephan , Heilbron Karl 
Published: July 2024

AbstractGenome-wide association studies (GWAS) help to identify disease-linked genetic variants, but pinpointing the most likely causal genes in GWAS loci remains challenging. Existing GWAS gene prioritization tools are powerful but often use complex black box models trained on datasets containing unaddressed biases. Here, we use a data-driven approach to construct a truth set of causal genes in 406 GWAS loci. We train a gene prioritization tool, CALDERA, that uses a simple logistic regression model with L1 regularization and corrects for potential confounders. Using three independent benchmarking datasets of resolved GWAS loci, we compare the performance of CALDERA with three other methods (FLAMES, L2G, and cS2G). CALDERA outperforms all these methods in two out of three datasets and ranks second in the remaining dataset. We demonstrate that CALDERA prioritizes genes with expected properties, such as mutation intolerance (OR = 1.751 for pLI > 90%, P = 8.45x10-3). Overall, CALDERA provides a powerful solution for prioritizing potentially causal genes in GWAS loci and may help identify novel genetics-driven drug targets.
GRAViTy-V2: a grounded viral taxonomy application
Authors: Mayne Richard , Aiewsakun Pakorn , Turner Dann , Adriaenssens Evelien M. , Simmonds Peter 
Published: July 2024

AbstractTaxonomic classification of viruses is essential for understanding their evolution and therefore their distribution, host interactions and pathogenic mechanisms. Classification methodologies usually rely on comparison of aligned sequence motifs in conserved genes, by genome organisation and gene complements, and at lower taxonomic ranks such as genus and species, through genome sequence identities. Building on our previous classification framework based on a novel whole-genome analysis method, we here describe Genome Relationships Applied to Viral Taxonomy Version 2 (GRAViTy-V2), which encompasses a greatly expanded range of features and numerous optimisations, packaged as an application that may be used as an alignment-free general-purpose virus classification tool. Using 28 datasets derived from the International Society on Taxonomy of Viruses 2022 taxonomy proposals, GRAViTy-V2 output was compared against human expert-curated classifications used for assignments in the 2023 round of ICTV taxonomy changes. GRAViTy-V2 produced taxonomies equivalent to manually-curated versions down to the family level and in almost all cases, to genus and species levels. However, discrepancies with our results primarily arose through various human and automated sequence annotation errors and erroneous annotations of coding sequences used in their original classification. Analysis times ranged from 1–506 min (median 3.59) on datasets with 17–1004 genomes and mean genome length of 3,000–1,000,000 bases, on a standard consumer-grade laptop. We discuss how the output from GRAViTY-V2 outputs allows for a full analysis of why taxonomic classifications were proposed, the value of the program for quality control of genetic comparisons, and how to optimise the speed of classification through proper use of GRAViTy-V2’s workflow management system.
A comprehensive analysis of the potential biological functions and prognostic values of SREBF1 for multiple cancer types including colorectal cancer
Authors: Li Dongling , Xu Fan , Cai Qinrui , Lin Ling , Zhou Xiaoya , Li Li , Chen Yao , Feng Tianlin , Gan Yuanxiu , Zhang Chenhua , Yang Fan 
Published: July 2024

AbstractAs an important molecule involved in lipid metabolism, Sterol Regulatory Element-Binding Protein 1 (SREBF1) plays a critical role in governing cellular lipid synthesis and uptake. However, a comprehensive understanding of the biological significance of SREBF1 in pan-cancer remains elusive. In this study, we aimed to comprehensively analyze the functional characteristics of SREBF1 in human cancers, including colorectal cancer (CRC). Our study utilized various databases and tools such as TCGA, GEO, TIMER2.0, GEPIA2.0, UALCAN, and the Human Protein Atlas to examine SREBF1 expression, genetic alterations, immune infiltration, single-cell sequencing, survival analysis, and gene enrichment. The results revealed that the expression of SREBF1 exhibited significant variations across different cancer types, and was closely associated with patient prognosis and immune infiltration. Moreover, the gene function assays indicated SREBF1 significantly affect cell growth and migration. Overall, the findings suggest that SREBF1 could serve as a potential prognostic biomarker and a novel therapeutic target in different cancer types.
Mapping the nuclear landscape with multiplexed super-resolution fluorescence microscopy
Authors: Rahman Fariha , Augoustides Victoria , Tyler Emma , Daugird Timothy A. , Arthur Christian , Legant Wesley R. 
Published: July 2024

AbstractThe nucleus coordinates many different processes. Visualizing how these are spatially organized requires imaging protein complexes, epigenetic marks, and DNA across scales from single molecules to the whole nucleus. To accomplish this, we developed a multiplexed imaging protocol to localize 13 different nuclear targets with nanometer precision in single cells. We show that nuclear specification into active and repressive states exists along a spectrum of length scales, emerging below one micron and becoming strengthened at the nanoscale with unique organizational principles in both heterochromatin and euchromatin. HP1-α was positively correlated with DNA at the microscale but uncorrelated at the nanoscale. RNA Polymerase II, p300, and CDK9 were positively correlated at the microscale but became partitioned below 300 nm. Perturbing histone acetylation or transcription disrupted nanoscale organization but had less effect at the microscale. We envision that our imaging and analysis pipeline will be useful to reveal the organizational principles not only of the cell nucleus but also other cellular compartments.
Habitat use of rewilded horses and cattle as related to the functional and structural composition of plant communities in a European restored wetland ecosystem
Authors: Lovász Lilla , Korner-Nievergelt Fränzi , Amrhein Valentin 
Published: July 2024

AbstractRewilding initiatives in European open and semi-open lowlands increasingly involve cattle and horses for ecological restoration, especially in wetland areas of high conservation value. These large herbivores contribute to spatial heterogeneity and enhance biodiversity by shaping ecosystems through movement, grazing, and resting behaviours. However, the effect of their site-specific habitat use patterns on plant communities remains unclear.In this study, we investigated the fine-scale spatiotemporal distribution of rewilded cattle and horses in a recently restored alluvial grassland in a French nature reserve. We explored differences in habitat use between the two species during summer and winter on a macrohabitat scale and examined structural and functional changes in vegetation traits over four years, focusing on plant height, patch cover, species richness, and light preference, nutrient-tolerance, and mowing/grazing tolerance of plants. The study site, a former agricultural area converted into a restored alluvial nature conservation site, allowed observation of ecological processes from a “zero state”.Our results suggest that cattle and horses exhibit similar habitat use with seasonal variations, potentially indicating partially shared feeding niches. The mixed-species grazing prevented vegetation overgrowth by keeping plant cover and vegetation height under control, yet without causing destructive impacts. The two herbivore species induced a clear increase in grazing-tolerant plants and slight changes in the abundance of light-preferring and nutrient-tolerant species.Synthesis: Overall, we found that the varying spatiotemporal distribution of rewilded horses and cattle likely induces changes in plant community on the patch scale but results in vegetation stability on the landscape scale, which is known to facilitate ecosystem functioning. Our study therefore informs managers of conservation initiatives, proposing rewilding with year-round grazing horses and cattle a promising strategy for ecological restoration and natural habitat maintenance in wetland areas.
CDK4/6 and SHP2 mediate BRAF/MEK inhibitor resistance in Class 2 and 3 BRAF mutant cancers
Authors: Rose April A. N. , Maxwell Jennifer , Rousselle Emmanuelle , Riaud Melody , Elkholi Islam E. , Mukonoweshuro Chantel , Biondini Marco , Cianfarano Erica , Soria-Bretones Isabel , Tobin Chantal , McGuire Meghan , King Ian , Zhang Tong , Pugh Trevor J. , Saeed Kamil Zaid , Shepherd Frances A. , Leighl Natasha , Abdul Razak Albiruni , Hansen Aaron , Saibil Sam , Bedard Philippe , Siegel Peter M. , Siu Lillian L. , Cescon David W. , Spreafico Anna 
Published: July 2024

AbstractClass 2 and 3 non-V600EBRAFmutations are oncogenic drivers in many cancer types. Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600EBRAFmutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600EBRAFmutations. The best objective response rate was 14% (3/21). By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and functional genomics of Class 2 & 3BRAFmutant cell lines, we discovered MAPK-dependent and independent mechanisms of intrinsic and acquired resistance to BRAF/MEK inhibition. These included the acquisition of new mutations inNRAS, MAP2K1, RAF1,andRBin ctDNA at the time of disease progression. We observed an enrichment for alterations in genes that regulate cell cycle progression amongst non-responders and increased expression of genes mediating cell cycle progression in tumors Class 2BRAFmutant cell lines with acquired resistance to BRAF/MEK inhibitors. In Class 3 BRAF mutant cancers specifically,PTPN11(SHP2) was an essential gene. CDK4/6 and SHP2 were found to mediate intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors were more effective than BRAF/MEK inhibitors alonein vitroandin vivo, highlighting the need to explore therapeutic targets outside of the MAPK pathway in these hard-to-treat Class 2 & 3BRAFmutant cancers.
Protein surface chemistry encodes an adaptive tolerance to desiccation
Authors: Romero-Pérez Paulette Sofía , Moran Haley M. , Horani Azeem , Truong Alexander , Manriquez-Sandoval Edgar , Ramirez John F. , Martinez Alec , Gollub Edith , Hunter Kara , Lotthammer Jeffrey M. , Emenecker Ryan J. , Liu Hui , Iwasa Janet H. , Boothby Thomas C. , Holehouse Alex S. , Fried Stephen D. , Sukenik Shahar 
Published: July 2024

AbstractCellular desiccation - the loss of nearly all water from the cell - is a recurring stress in an increasing number of ecosystems that can drive protein unfolding and aggregation. For cells to survive, at least some of the proteome must resume function upon rehydration. Which proteins tolerate desiccation, and the molecular determinants that underlie this tolerance, are largely unknown. Here, we apply quantitative and structural proteomic mass spectrometry to show that certain proteins possess an innate capacity to tolerate rehydration following extreme water loss. Structural analysis points to protein surface chemistry as a key determinant for desiccation tolerance, which we test by showing that rational surface mutants can convert a desiccation sensitive protein into a tolerant one. Desiccation tolerance also has strong overlap with cellular function, with highly tolerant proteins responsible for production of small molecule building blocks, and intolerant proteins involved in energy-consuming processes such as ribosome biogenesis. As a result, the rehydrated proteome is preferentially enriched with metabolite and small molecule producers and depleted of some of the cell’s heaviest consumers. We propose this functional bias enables cells to kickstart their metabolism and promote cell survival following desiccation and rehydration.TeaserProteins can resist extreme dryness by tuning the amino acids on their surfaces.
pH-dependent direct sulfhydrylation pathway is required for the pathogenesis ofMycobacterium tuberculosis
Authors: Nain Vaibhav Kumar , Barik Vishawjeet , Pandey Manitosh , Pareek Mohit , Sharma Taruna , Pal Rahul , Tyagi Shaifali , Bajpai Manish , Dwivedi Prabhanjan , Panda Bhishma Narayan , Kumar Yashwant , Asthana Shailendra , Pandey Amit Kumar 
Published: July 2024

AbstractMethionine is essential for the survival ofMycobacterium tuberculosis(M. tuberculosis) inside the host. However, the transsulfuration pathway, a major contributor of methionine, is dispensable for the growth ofM. tuberculosissuggesting redundancy in the methionine biosynthesis pathway. Orthologues of MetZTBin other bacterial species are known to operate a redundant single-step methionine biosynthesis pathway calleddirect sulfhydrylation.In this study, we demonstrate that genetic disruption of themetZ-mediated direct sulfhydrylation pathway inM. tuberculosishinders growth at low pH, an effect mitigated by methionine supplementation. Computational analyses, includingin-silicomolecular docking and molecular dynamics (MD) simulations, reveal enhanced binding of the MetZ substrate, O-succinyl homoserine (OSH), to the active site of MetZ at acidic pH. Intriguingly, despite increased intracellular ATP levels, a relative decrease in the frequency of Bedaquiline (BDQ)-induced persisters is observed inmetZ-deficient strain, suggesting a role of direct sulfhydrylation pathway in modulating BDQ sensitivity. Finally, we demonstrated that the absence ofmetZimpedes the ability ofM. tuberculosisto grow inside the host.
Proteomic analysis reveals the dominant effect of ipomoeassin F on the synthesis of membrane and secretory proteins in triple-negative breast cancer cells
Authors: Sicairos Brihget , Zhou Jianhong , Hu Zhijian , Zhang Qingyang , Shi Wei Q , Du Yuchun 
Published: July 2024

AbstractIpomoeassin F (Ipom-F) is a natural compound with embedded carbohydrates that exhibits a potent cytotoxic effect on triple-negative breast cancer (TNBC) cells. The mechanism behind this selective potency remains unclear. To elucidate this mechanism, we analyzed the proteome profiles of the TNBC MDA-MB-231 cells after exposure to Ipom-F at different time points and increasing doses using a quantitative proteomic method. Our proteomic data demonstrate that the major effect of Ipom-F on MDA-MB-231 cells is the inhibition of membrane and secreted protein expression. Our proteomic data are consistent with the recently uncovered molecular mechanism of action of Ipom-F, which binds to Sec61-α and inhibits the co-translational import of proteins into the endoplasmic reticulum. We have defined a subset of membrane and secreted proteins particularly sensitive to Ipom-F. Analysis of the expression of these Ipom-F-sensitive proteins in cancer cell lines and breast cancer tissues demonstrates that some of these proteins are upregulated in TNBC cells. Thus, it is likely that TNBC cells may have adapted to the elevated levels of some proteins identified as sensitive to Ipom-F in this study; inhibition of the expression of these proteins leads to a crisis in proliferation and/or survival for the cells.
Modulation of Electrostatic Interactions as a Mechanism of Cryptic Adaptation ofColwelliato High Hydrostatic Pressure
Authors: Makhatadze George I. 
Published: July 2024

AbstractThe role of various interactions in determining the pressure adaptation of the proteome in piezophilic organisms remains to be established. It is clear that the adaptation is not limited to one or two proteins, but has a more general evolution of the characteristics of the entire proteome, the so-called cryptic evolution. Using the synergy between bioinformatics, computer simulations, and some experimental evidence, we probed the physico-chemical mechanisms of cryptic evolution of the proteome of psychrophilic strains of model organism,Colwellia, to adapt to life at various pressures, from the surface of the Arctic ice to the depth of the Mariana Trench. From the bioinformatics analysis of proteomes of several strains of Colwellia, we have identified the modulation of interactions between charged residues as a possible driver of evolutionary adaptation to high hydrostatic pressure. The computational modeling suggests that these interactions have different roles in modulating the function-stability relationship for different protein families. For several classes of proteins, the modulation of interactions between charges evolved to lead to an increase in stability with pressure, while for others, just the opposite is observed. The latter trend appears to benefit enzyme activity by countering structural rigidification due to the high pressure.
Quantitative assessment and spatial distribution ofPlasmopara viticolaoospores in vineyard soil
Authors: Poeydebat Charlotte , Courchinoux Eva , Demeaux Isabelle , Rodriguez Marie , Chataigner Alexandre , Lelièvre Mélanie , Goutouly Jean-Pascal , Rossi Jean-Pierre , Raynal Marc , Delière Laurent , Delmotte François 
Published: July 2024

AbstractGrapevine downy mildew, caused by the oomycetePlasmopara viticola, is one of the most devastating diseases of grapevine worldwide. While primary inoculum plays a decisive role in disease epidemics, we still know very little about the abundance and the distribution of oospores, which are the overwintering forms of the pathogen resulting from sexual reproduction. In this study, we used ddPCR to describe the spatial distribution ofP. viticolainoculum in a vineyard soil at the onset of the growing season. We foundP. viticolaoospores in all soil samples except one. The distribution of primary inoculum at the field scale was not random but characterized by 25 m-diameter patches of concentrically increasing oospore concentration. There was a positive coregionalization between soil inoculum and soil moisture spatial distributions, possibly mediated by disease incidence. The results indicated that oospores accumulated 5 times more in the ridge of soil below the vine stocks than in the inter-row. We conducted a leaf disc bioassay to assess soil infectious potential on a subset of samples collected in the field. Soil infectious potential estimated through infected leaf-disc area was positively correlated with our DNA-based quantification of oospores. Overall, the quantitative and spatially explicit survey of primary inoculum reservoir gained from these molecular and biological methods will contribute to the design of management strategies aimed at preventing primary inoculum accumulation in the vineyard from one season to the next.
Unveiling shadows: exploring the dark side of digital transformation in Abu Dhabi
Authors: Badri Masood , Alkhaili Mugheer , Aldhaheri Hamad , Yang Guang , Albahar Muna , Yaageib Saad , Alrashdi Asma 
Published: July 2024

PurposeThis research aims to investigate the negative aspects of digital transformation (DT) impacting various segments of society in the Emirate of Abu Dhabi, one of the seven Emirates comprising the United Arab Emirates. Specifically, it focuses on perceptions of participants to well-being: social connections and activities, physical health, mental health, the impact on the younger generation, and security/cybercrime.Design/methodology/approachUsing data from the 3rd Abu Dhabi Quality of Life Survey, which is an annual large-scale survey, this study employs analysis of variance and regression analysis to explore the associations between the perceived negative impact of DT and various well-being indicators.FindingsThe study reveals that the perceived negative impact of digital transformation on the younger generation is of the highest concern, followed by concerns about mental health and social relationships. Results also show significant variations among different demographic categories. Among the perceived negative impacts, mental health, social trust, and happiness emerge as the most affected well-being indicators.Originality/valueThe originality and value of this study lie in its large social survey sample of over 80,000 participants. The findings suggest that the negative effects of DT are not uniformly experienced across different segments of the population. The study highlights the need for further research on the adverse effects of DT and recommends that policymakers develop targeted strategies to address the specific needs of different community segments, particularly vulnerable groups. Additionally, it emphasizes the importance of adaptive policies for younger age groups to prepare them for a digital future.