bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review and Meta-analysis of Polycystic Ovary Syndrome and Mental Health among Black Asian Minority Ethnic populations
Authors: Delanerolle Gayathri , Ayis Salma , Barzilova Vanya , Phiri Peter , Zeng Yutian , Ranaweera Sandali , Shetty Ashish , Haque Nyla , Kar Debasish , Majumder Kingshuk , Rathod Shanaya , Raymont Vanessa , Shi Jian Qing , Hapangama Dharani K. 
Published: March 2022

AbstractBackgroundPolycystic Ovary Syndrome (PCOS) is a chronic and a common gynaecological condition impacting women of reproductive age. Women with PCOS have hormonal, ovulatory and metabolic dysfunction resulting in multiple symptoms. The correlation between hormonal disbalance and the impact on women’s mental health (MH) has been researched for decades. However, the prevalence among different ethnicities has not been fully evaluated.MethodsA systematic methodology was developed, and a protocol was published in PROSPERO (CRD42020210863) and a systematic review of publications between 1st January 1990-30th January 2021 was conducted. Multiple electronic databases were explored using keywords and MeSH terms. The finalised dataset was analysed using statistical methods such as random-effect models, subgroup analysis and sensitivity analysis.FindingsWe included 30 studies reporting on 3,944 PCOS women. Majority of studies addressed depression anxiety, and common mental health. Studies had fair to poor methodological quality and includes observational studies and Randomised Clinical Trials (RCTs). Overall, 17% (95% CI: 7% to 29%) of women with PCOS have clinical diagnosis of major or severe depression; 33% (95% CI: 26% to 40%) have elevated depressive symptoms or a clinical diagnosis of depression; 41% (95% CI: 28% to 54%) report anxiety symptoms, and 31% (95% CI: 15% to 51%) have a form a common mental health or are takingpsychiatric medication for anxiety and / or depression. The use of various tools to assess mental health symptoms was among the reasons for the substantial heterogeneity across studies.InterpretationPCOS is associated with an increased risk of mental health disorders including depressive s, anxiety, and other mental health disorders. While BAME populations account for about 20% of most of the samples studied, stratification by ethnicity was rarely attempted which made it difficult to elucidate the MH impact of PCOS on different communities.FundingNot applicablePROSPERO registration numberCRD42020210863
A guide to examining intramuscular fat formation and its cellular origin in skeletal muscle
Authors: Johnson Connor D. , Zhou Lylybell Y. , Kopinke Daniel 
Published: March 2022

ABSTRACTFibro-adipogenic progenitors (FAPs) are mesenchymal stromal cells that play a crucial role during skeletal muscle homeostasis and regeneration. FAPs build and maintain the extracellular matrix that acts as a molecular myofiber scaffold. In addition, FAPs are indispensable for myofiber regeneration as they secrete a multitude of beneficial factors sensed by the muscle stem cells (MuSCs). In diseased states, however, FAPs are the cellular origin of intramuscular fat and fibrotic scar tissue. This fatty fibrosis is a hallmark of sarcopenia and neuromuscular diseases, such as Duchenne Muscular Dystrophy. One significant barrier in determining why and how FAPs differentiate into intramuscular fat is effective preservation of adipocytes, especially in frozen tissue sections. Conventional methods of skeletal muscle tissue processing, such as snap-freezing, do not properly preserve the morphology of individual adipocytes, thereby preventing accurate visualization and quantification. Here, we describe a protocol that provides robust preservation of adipocyte morphology in skeletal muscle sections allowing visualization, imaging, and quantification of intramuscular fat. We also outline how to process a portion of muscle tissue for RT-qPCR, enabling users to confirm observed changes in fat formation by viewing differences in expression of adipogenic genes. Additionally, we will describe how our protocol can be adopted to visualize adipocytes by whole mount immunofluorescence of muscle samples. Finally, we will outline how to combine this protocol with genetic lineage tracing of Pdgfrα-expressing FAPs to study the adipogenic conversion of FAPs. Our protocol consistently yields high-resolution and morphologically accurate immunofluorescent images of adipocytes that, along with confirmation by RT-qPCR, allows for robust, rigorous, and reproducible visualization and quantification of intramuscular fat. Together, our analysis pipeline is the first step to improve our understanding of how FAPs differentiate into intramuscular fat and provides a framework to validate novel interventions to prevent fat formation.
Cell Chromatography: Biocompatible chromatographic separation and interrogation of microbial cells
Authors: Hazu M. , Ahmed A. , Curry E. , Hornby D.P. , Gjerde D.T. 
Published: March 2022

AbstractThe isolation of pure, single colonies lies at the heart of experimental microbiology. However, a microbial colony typically contains around one million cells at all stages of the life cycle. Here we describe a novel, cell chromatography method that facilitates the capture, purification and interrogation of microbial cells from both single and mixed cultures. The method described relies on, but is not limited to, differences in surface charge to separate bacterial strains. The method is fully biocompatible, leading to no significant loss of cell viability,. The chromatographic capture of cells, combined with selective elution methods facilitates a greater level of experimental control over the sample inputs required for downstream high throughput and high sensitivity, analytical methods. The application of the method for interrogating the antibiotic resistance of bacterial strains and for the separation of bacteria from environmental samples is illustrated.
Extraction of individual associative memory related dominant theta frequency for personalized transcranial brain stimulation
Authors: Bjekić Jovana , Paunovic Dunja , Živanović Marko , Stanković Marija , Griškova-Bulanova Inga , Filipović Saša R. 
Published: March 2022

AbstractNon-invasive brain stimulation (NIBS) has gained increased interest in research and therapy of associative memory (AM) and its impairments. However, the one-size-fits-all approach yields inconsistent findings, thus putting forward the need for the development of personalized frequency-modulated NIBS protocols to increase the focality and the effectiveness of the interventions. There have been only a few attempts to deliver theta frequency-personalized tES. The current study explores the feasibility of determining dominant individual theta-band frequency (ITF) based on AM task evoked EEG activity. In a sample of 42 healthy young adults, we extracted the frequencies (2-15 Hz, in 0.5 Hz steps) with the highest event-related spectral perturbation from the EEG recorded during successful encoding in the AM task. The developed method for extraction of the dominant theta-band frequency based on the AM-evoked EEG changes is able to reliably determine the AM-related ITF and can be used for personalization of the oscillatory NIBS techniques.
Structural analogue-based protein structure domain assembly assisted by deep learning
Authors: Peng Chun-Xiang , Zhou Xiao-Gen , Xia Yu-Hao , Liu Jun , Hou Ming-Hua , Zhang Gui-Jun 
Published: March 2022

AbstractMotivationWith the breakthrough of AlphaFold2, the protein structure prediction problem has made a remarkable progress through end-to-end deep learning techniques, in which correct folds could be built for nearly all single-domain proteins. However, the full-chain modelling appears to be lower on average accuracy than that for the constituent domains and requires higher demand on computing hardware, indicating the performance of full-chain modelling still needs to be improved. In this study, we investigate whether the predicted accuracy of full-chain model can be further improved by domain assembly assisted by deep learning.ResultsIn this article, we developed a structural analogue-based protein structure domain assembly method assisted by deep learning, named SADA. In SADA, a multi-domain protein structure database (MPDB) was constructed for the full-chain analogue detection using individual domain models. Starting from the initial model constructed from the analogue, the domain assembly simulation was performed to generate the full-chain model through a two-stage differential evolution algorithm guided by the physics-based force field and an inter-residue distance potential predicted by deep learning. SADA was compared with the state-of-the-art domain assembly methods on 356 benchmark proteins, and the average TM-score of SADA models is 8.1% and 27.0% higher than that of DEMO and AIDA, respectively. We also assembled full-chain models of 20 human multi-domain proteins using individual domain models independently predicted by AlphaFold2, where the SADA full-chain models obtained a 4.8% higher average TM-score than full-chain models directly predicted by AlphaFold2 and fewer computing resources were required. In addition, we also find that the domains often interact in the similar way in the quaternary orientations if the domains have similar tertiary structures. Furthermore, homologous templates and structural analogues are complementary for multi-domain protein full-chain modelling.AvailabilityThe SADA web server are freely available at http://zhanglab-bioinf.com/SADA.
Low memory T cells blood counts and high naïve regulatory T cells percentage at relapsing remitting multiple sclerosis diagnosis
Authors: Canto-Gomes João , Silva Carolina S. , Rb-Silva Rita , Boleixa Daniela , Silva Ana Martins da , Cheynier Rémi , Costa Patrício , González-Suárez Inés , Correia-Neves Margarida , Cerqueira João , Nobrega Claudia 
Published: March 2022

AbstractObjectiveTo assess the peripheral immune system of newly diagnosed relapsing remitting multiple sclerosis (RRMS) patients and compare it to healthy controls (HC).MethodsCross-sectional study with 30 treatment-naïve newly diagnosed RRMS patients, and 33 sex and age-matched HC. Their peripheral blood mononuclear cells were analysed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naïve and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on T cells subsets; iv) regulatory T cell (Tregs) phenotype; and vi) expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence.ResultsNewly diagnosed RRMS patients and HC have equivalent thymic function as determined by similar numbers of RTEs, and levels of sjTRECs, DJβTRECs and sj/DJβTREC ratio. In the CD8+ T cells compartment RRMS patients have a higher naïve/memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Among CD4+ T cells lower blood counts of effector memory cells are found in patients upon controlling for sex, age and HCMV IgG seroprevalence. RRMS patients have higher percentage of naive Tregs comparing to HC. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1, and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells. MS severity and time from relapse correlate with immune cells alterations.ConclusionCharacterization of the peripheral immune system of treatment-naïve newly diagnosed RRMS patients unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naïve Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.
Structural basis of Ty1 integrase tethering to RNA polymerase III for targeted retrotransposon integration
Authors: Nguyen Phong Quoc , Huecas Sonia , Asif-Laidin Amna , Plaza-Pegueroles Adrián , Palmic Noé , Acker Joël , Reguera Juan , Lesage Pascale , Fernández-Tornero Carlos 
Published: March 2022

SummaryThe yeast Ty1 retrotransposon integrates upstream of genes transcribed by RNA polymerase III (Pol III). Specificity of integration is mediated by an interaction between the Ty1 integrase (IN1) and Pol III, currently uncharacterized at the atomic level. Here, we report cryo-EM structures of Pol III in complex with IN1, revealing a 16-residue segment at the IN1 C-terminus that contacts Pol III subunits AC40 and AC19, an interaction that we validate byin vivomutational analysis. Unexpectedly, IN1 binding associates with insertion of subunit C11 C-terminal Zn-ribbon into the Pol III funnel, which provides atomic evidence for a two-metal mechanism during RNA cleavage. Moreover, unstructured regions of subunits C53 and C37 reorganize close to C11, likely explaining the connection between the C37/C53 heterodimer and C11 during transcription reinitiation. Our results suggest that IN1 binding induces a Pol III configuration that favors chromatin residence, thus improving the likelihood of Ty1 integration.
Comparative analysis of the Illumina Mouse Methylation BeadChip and Reduced Representation Bisulphite Sequencing for routine DNA methylation analysis of murine samples
Authors: Fennell Lochlan J , Hartel Gunter , McKeone Diane M , Bond Catherine E , Kane Alexandra , Leggett Barbara A , Patch Ann-Marie , Whitehall Vicki LJ 
Published: March 2022

AbstractBackgroundResearching the murine epigenome in disease models has been hampered by the lack of an appropriate and cost-effective DNA methylation array. Until recently, investigators have been limited to the relatively expensive and analysis intensive bisulphite sequencing methods. Here, we performed a comprehensive, comparative analysis between the new Mouse Methylation BeadChip (MMB) and reduced representation bisulphite sequencing (RRBS) in two murine models of colorectal carcinogenesis, providing insight into the utility to each platforms in a real world environment.ResultsWe captured 1.47×106 CpGs by RRBS and 2.64×105 CpGs by MMB, mapping to 13,778 and 13,365 CpG islands, respectively. RRBS captured significantly more CpGs per island (median 41 for RRBS versus 2 for MMB). We found that 64.4% of intra-island CpG methylation variability can be captured by measuring approximately one quarter of CpG island (CGI) CpGs. MMB was more precise in measuring DNA methylation, especially at sites that had low RRBS coverage. This impacted differential methylation analysis, with more statistically significantly differentially methylated CpG sites identified by MMB in all experimental conditions, however the difference was minute when appropriate thresholding for the magnitude of methylation change (0.2 beta value difference) was applied, providing confidence that both techniques can identify similar differential DNA methylation. Gene ontology enrichment analysis of differentially hypermethylated gene promoters identified similar biological processes and pathways by both RRBS and MMB across two murine model systems.ConclusionMMB is an effective tool for profiling the murine methylome that performs comparably to RRBS, identifying similar differentially methylated pathways. Although MMB captures a similar proportion of CpG islands, it does so with fewer CpGs per island. We show that subsampling informative CpGs from CpG islands is an appropriate strategy to capture whole island variation. Choice of technology is experiment dependent and will be predicated on the underlying biology being probed.
Dentate gyrus mossy cells exhibit sparse coding via adaptive spike threshold dynamics
Authors: Trinh Anh-Tuan , Girardi-Schappo Mauricio , Béïque Jean-Claude , Longtin André , Maler Leonard 
Published: March 2022

AbstractHilar mossy cells (hMCs) are glutamatergic neurons in the dentate gyrus (DG) that receive inputs primarily from DG granule cells (GCs), CA3 pyramidal cells and local inhibitory interneurons. The hMCs then provide direct excitatory and disynaptic inhibitory feedback input to GCs. Behavioral and in vivo single unit recording experiments have implicated hMCs in pattern separation as well as is in spatial navigation and learning. It has, however, been difficult to mechanistically link the in vivo physiological behavior of hMCs with their intrinsic excitability properties that convert their synaptic inputs into spiking output. Here, we carried out electrophysiological recordings from the main cell types in the DG and found that hMCs displayed a highly adaptive threshold acting over a remarkably protracted time-scale. The hMC spike threshold increased linearly with increasing current stimulation and saturated at high current intensities. This threshold also increased in response to spiking and this effect also decayed over a long timescale, allowing for activity-dependent summation that limited hMC firing rates. This mechanism operates in parallel with a prominent medium after-hyperpolarizing potential (AHP) generated by the small conductance K+ channel. Based on experimentally derived parameters, we developed a phenomenological exponential integrate-and-fire model that closely mimics the hMC adaptive threshold. This lightweight model is amenable to its incorporation into large network models of the DG that will be conducive to deepen our understanding of the neural bases of pattern separation, spatial learning and navigation in the hippocampus.Statement of significanceRecent studies on hilar mossy cells have revealed that they are implicated in spatial navigation and mnemonic functions. Yet, the basic intrinsic characterization of these hMCs is still too superficial to explain their spiking behavior in vivo. Here, we describe novel biophysical properties of hMCs, including an independent relationship between spike latency and spike threshold as well as a slowly adapting spike threshold. These findings complement several other biophysical and connectivity similarities between hMCs and CA3 pyramidal cells, while emphasizing the contrast with hilar interneurons. Additionally, our results are well captured by a phenomenological model of the hMC which provides a useful framework to study the neural substrate of spatial navigation and learning in the dentate gyrus.
Generation and Maturation of Human iPSC-derived Cardiac Organoids in Long Term Culture
Authors: Ergir Ece , La Cruz Jorge Oliver-De , Fernandes Soraia , Cassani Marco , Niro Francesco , Sousa Daniel , Vrbský Jan , Vinarský Vladimír , Perestrelo Ana Rubina , Debellis Doriana , Cavalieri Francesca , Pagliari Stefania , Redl Heinz , Ertl Peter , Forte Giancarlo 
Published: March 2022

ABSTRACTCardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited.We have established a scaffold-free protocol to generate multicellular, beating and self-organized human cardiac organoids (hCO) in vitro from hiPSCs that can be cultured for long term. This is achieved by differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated human cardiac organoids (hCOs) containing multiple cell types that physiologically compose the heart, gradually self-organize and beat without external stimuli for more than 50 days. We have shown that 3D hCOs display improved cardiac specification, survival and maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hCOs by their response to cardioactive drugs in long term culture. Furthermore, we demonstrated that hCOs can be used to study chemotherapy-induced cardiotoxicity.This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.
Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary
Authors: Singh Neha , Singh Domdatt , Bhide Anshul , Sharma Richa , Sahoo Sarthak , Jolly Mohit Kumar , Modi Deepak 
Published: March 2022

AbstractLIM-homeobox genes play multiple roles in developmental processes, but their roles in gonad development are not completely understood. Herein, we report that Lhx2, Ils2, Lmx1a, and Lmx1b are expressed in a sexually dimorphic manner in mouse, rat, and human gonads during sex determination. Amongst these, Lhx2 has female biased expression in the developing gonads of species with environmental and genetic modes of sex determination. Single-cell RNAseq analysis revealed that Lhx2 is exclusively expressed in the germ cells of the developing mouse ovaries. To elucidate the roles of Lhx2 in the germ cells, we analyzed the phenotypes of Lhx2 knockout XX gonads. While the gonads developed appropriately in Lhx2 knockout mice and the somatic cells were correctly specified in the developing ovaries, transcriptome analysis revealed enrichment of genes in the angiogenesis pathway. There was an elevated expression of several pro-angiogenic factors in the Lhx2 knockout ovaries. The elevated expression of pro-angiogenic factors was associated with an increase in numbers of endothelial cells in the Lhx2-/-ovaries at E13.5. Gonad recombination assays revealed that the increased numbers of endothelial cells in the XX gonads in absence of Lhx2 was due to ectopic migration of endothelial cells in a cell non-autonomous manner. We also found that, there was increased expression of several endothelial cell-enriched male-biased genes in Lhx2 knockout ovaries. Also, in absence of Lhx2, the migrated endothelial cells formed an angiogenic network similar to that of the wild type testis, although the coelomic blood vessel did not form. Together, our results suggest that Lhx2 in the germ cells is required to suppress vascularization in the developing ovary. These results suggest a need to explore the roles of germ cells in the control of vascularization in developing gonads.Abstract FigureHighlightMultiple LIM-HD genes are expressed in developing gonads during the window of sex determination with Lhx2 having female dominating expression in an evolutionarily conserved mannerLhx2 is expressed in the germ cells of developing mouse ovariesLoss of Lhx2 in the developing ovaries alters the expression of genes involved in various pathways including angiogenesisLhx2 in germ cells suppress endothelial cell migration in the developing ovaries
Promising Antimalarials targeting Apicoplast DNA Polymerase from Plasmodium falciparum
Authors: Chheda Pratik R. , Nieto Nicholas , Kaur Supreet , Beck John M. , Beck Josh R. , Honzatko Richard , Kerns Robert J. , Nelson Scott W. 
Published: March 2022

ABSTRACTMalaria is caused by the parasite Plasmodium falciparum, which contains an essential non-photosynthetic plastid called the apicoplast. A single DNA polymerase, apPOL, is targeted to the apicoplast, where it replicates and repairs the genome. apPOL has no direct orthologs in mammals and is considered a promising drug target for the treatment and/or prevention of malaria. We previously reported screening the Malaria Box to identify MMV666123 as an inhibitor of apPOL. Herein we extend our studies and report structure-activity relationships for MMV666123 and identify key structural motifs necessary for inhibition. Although attempts to crystallize apPOL with the inhibitor were not fruitful, kinetic analysis and crystal structure determinations of WT and mutant apo-enzymes, facilitated model building and provided insights into the putative inhibitor binding site. Our results validate apPOL as an antimalarial target and provide an avenue for the design of high potency, specific inhibitors of apPOL and other A-family DNA polymerases.