bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of exercise on fatigue in patients receiving maintenance hemodialysis treatment: A systematic review and network meta-analysis
Authors: Lu Xianying , Yang Jing , Bai Dingxi , Wu Chenxi , Cai Mingjin , Wang Wei , He Jiali , Gong Xiaoyan , Gao Jing , Hou Chaoming 
Published: October 2023

AbstractObjectiveThis study aimed to evaluate the effect of different exercises for improving fatigue in maintenance hemodialysis patients.DesignPubMed, Embase, Web of Science, Cochrane, PEDro, CNKI, VIP, Wanfang data, CBM, and CINAHL were conducted from the establishment of the database to July 2023. We independently screened the literature, evaluated the quality, analyzed the data using Stata 15.0, and performed subgroup analysis on intervention time and exercise intervention adherence.ResultsTwenty-three studies were analyzed, with 1,867 patients and nine interventions. Based on the surface under cumulative ranking curves (SUCRA) and pairwise comparisons effects, overall long-term, short-term, and exercise intervention adherence >90% effects have all presented that during dialysis aerobic-resistance combined exercise (DDAR) was ranked as the most effective compared with routine care (SUCRC: 83.9%, SMD = -1.45, 95% CI (-2.23, -0.67); SUCRC: 85.9%, SMD = -1.38, 95% CI (-2.24, -0.52); SUCRC: 86.6%, SMD = -1.54, 95%CI (-2.58, -0.49); SUCRC: 83.6%, SMD = -1.45, 95% CI (-2.25, -0.66), respectively), followed by interdialytic period muscle relaxation exercise, interdialytic period aerobic-resistance combined exercise, interdialytic period aerobic exercise, and interdialytic period Baduanjin.ConclusionDDAR may be considered in practice when resources allow. However, high-quality, multi-center, and large-sample randomized control trials must further verify this conclusion.
The human LIN28B nucleosome is inherently pre-positioned for efficient binding of multiple OCT4s without H3 K27 acetylation
Authors: Lian Tengfei , Guan Ruifang , Zhou Bing-Rui , Bai Yawen 
Published: October 2023

AbstractPioneer transcription factors possess the unique ability to access DNA within tightly packed chromatin structures, playing pivotal roles in cell differentiation and reprogramming. However, their precise mechanism for recognizing nucleosomes has remained mystery. Recent structural and biochemical investigations into the binding interactions between the human pioneer factor OCT4 and the LIN28B nucleosome by Sinha et al.1and Guan et al.2have yielded conflicting results regarding nucleosome positioning, nucleosomal DNA unwrapping, binding cooperativity, and the role of N-terminal tail of OCT4. In this study, we undertook a comparative analysis of these two research efforts and delved into the factors contributing to the observed discrepancies. Our investigation unveiled that the utilization of human and Xenopus laevis core histones, along with a discrete two-step salt dialysis method, led to distinct positioning of DNA within reconstituted LIN28B nucleosomes. Additionally, our reanalysis of the electrophoretic mobility shift assay data showed that H3 K27 acetylation did not increase OCT4 binding to the internal sites of the nucleosome when normalized to input; instead, it promoted sample aggregation. Thus, the available experimental data support the notion that the human LIN28B nucleosome is pre-positioned for efficient binding with multiple OCT4s, and there is no compelling evidence for its regulation by histone modifications.
Merging-limited coarsening governs long-term stability of nanoscale condensates
Authors: Chen Feipeng , Zhang Yaojun , Shum Ho Cheung 
Published: October 2023

AbstractDroplet coarsening occurs in a variety of fields, characterized by the spontaneous growth of smaller droplets into larger ones to minimize their interfacial free energy and achieve global thermodynamic equilibrium. However, recent studies revealed that the coarsening is much suppressed in living cells where nanoscale biomolecular condensates with droplet-like behaviors maintain stable sizes over extended time periods. The mechanism underpinning such long-term stability of condensates remains poorly understood. Here, we experimentally observe that coacervate droplets of small sizes (tens to hundreds of nanometers) remain stable over hours with significantly slower coarsening rates than predicted by classic theories. Using scaling analysis and Monte Carlo simulations, we demonstrate that the anomalously stable coacervates can be explained by a merging-limited coarsening (MLC), in which merging probability among coacervates of sizes smaller than a critical valuebecomes markedly low, whereηis the internal viscosity and γ is the interfacial tension of droplets. We further develop an analytical model that quantitatively captures the coarsening dynamics of coacervates across different experimental conditions. More broadly, by constructing a viscosity-interfacial tension diagram, we find that many biological condensates intrinsically exhibit large critical sizes, making them prone to undergo slow coarsening through the MLC mechanism. Such merging-limited coarsening may represent a universal mechanism underlying condensate size control in synthetic systems and living cells.
Transposon-triggered epigenetic chromatin dynamics modulate EFR-related pathogen response
Authors: Mencia Regina , Arce Agustín L. , Houriet Candela , Xian Wenfei , Contreras Adrián , Shirsekar Gautam , Weigel Detlef , Manavella Pablo A. 
Published: October 2023

SummaryInfectious diseases drive the evolution of wild plants and impact yield in crop plants. Like animals, plants can sense biotic threats via conserved pathogen-associated patterns (PAMPs). Since an overly robust immune response can harm plants, understanding the mechanisms for tuning defense responses to the appropriate level is vital as we endeavor to develop pathogen-resistant crops. In this paper, we studied the Arabidopsis pattern recognition receptor (PRR) EFR, which senses bacterial EF-Tu. An inverted-repeat transposon (Ea-IR) betweenEFRand the neighboringXI-klocus controls local chromatin organization, promoting the formation of a repressive chromatin loop. Upon pathogen infection, the chromatin landscape aroundEFRandXl-kdynamically changes to allow for increasedEFRtranscription. Chromatin opening facilitates the passage of RNA polymerase II across the neighboringXI-kgene termination site, leading to a longerXI-ktranscript that includesEa-IRsequences. Dicer-like (DCL) enzymes process the longer Xl-k transcript into small RNAs (sRNAs), which reset chromatin topology to a repressive state, attenuating, in turn, the immune response, reminiscent of attenuation of receptor signaling in other systems. From an evolutionary point of view, we found that natural Arabidopsis accessions missingEa-IRhave a constitutive "EFR-open" chromatin configuration that correlates with higher basal EFR levels and higher background resistance to pathogens. Collectively, our study offers evidence for a scenario in which a transposon, chromatin organization, and gene expression interact to fine-tune immune responses, both during the course of infection and in the course of evolution. Similar gene-associated IRs in crops could provide valuable non-coding targets for genome editing or assisted plant breeding programs.
Combinatorial cooperativity can facilitate epithelial-mesenchymal transition in a miR200-Zeb feedback network
Authors: Rashid Mubasher , Devi Brasanna M , Banerjee Malay 
Published: October 2023

AbstractCarcinoma cells often utilize epithelial-mesenchymal transition (EMT) programs for cancer progression and metastasis. Numerous studies point to the SNAIL-induced miR200/Zeb feedback circuit as crucial in regulating EMT by shifting cancer cells to at least three (epithelial (E), hybrid (h E/M), mesenchymal (M)) phenotypic states arrayed along the epithelial-mesenchymal phenotypic spectrum. However, a coherent molecular-level understanding of how such a tiny circuit controls carcinoma cell entrance into and residence in various states is lacking. Here, we use molecular binding data and mathematical modeling to report that miR200/Zeb circuit can essentially utilize combinatorial cooperativity to control E-M phenotypic plasticity. We identify minimal combinatorial cooperativities that give rise to E, hybrid-E/M, and M phenotypes. We show that disrupting a specific number of miR200 binding sites on Zeb as well as Zeb binding sites on miR200 can have phenotypic consequences – the circuit can dynamically switch between two (E, M) and three (E, hybrid-E/M, M) phenotypes. Further, we report that in both SNAIL-induced and SNAIL knock-out miR200/Zeb circuits, cooperative transcriptional feedback on Zeb as well as Zeb translational inhibition due to miR200 are essential for the occurrence of intermediate hybrid-E/M phenotype. Finally, we demonstrate that SNAIL can be dispensable for EMT, and in the absence of SNAIL, the transcriptional feedback can control cell state transition from E to hybrid-E/M, to M state. Our results thus highlight molecular-level regulation of EMT in miR200/Zeb circuit and we expect these findings to be crucial to future efforts aiming to prevent EMT-facilitated dissemination of carcinomas.
NOXA/MCL-1 axis determines cell-death decision between apoptosis and pyroptosis and the inflammatory secretome of breast cancer cells treated with anti-mitotics
Authors: Dumont Alison , Gautier Fabien , Batard Quentin , Guette Catherine , Guillonneau François , Campone Mario , Juin Philippe , Barillé-Nion Sophie 
Published: October 2023

ABSTRACTUnderstanding how the malignant cells respond to chemotherapy is essential to prevent the development of resistance and to improve the efficiency of anti-cancer drugs. Recently, we established that, by intrinsic and paracrine mechanisms, taxol treatment in breast tumor cells increases NOXA a pro-apoptotic protein functioning as an endogenous inhibitor of survival protein MCL-1, thereby enhancing cytotoxic load on the compensatory survival protein BCL-xL. We herein sought to define the contribution of NOXA/MCL-1 to the modality of cell death secretome composition upon anti-mitotic treatment associated with a BCL-xL antagonist.We observed that genetic inactivation of NOXA (enforcing MCL-1 pro-survival activity) in cancer cells not only delays their death when exposed to taxol in combination with the BCL-xL antagonist A1331852, but also alters its morphological characteristics with the apparition of features evoking pyroptosis. We identified the Caspase3-GSDME axis as regulating pyroptotic-like features suggesting that NOXA may act as a negative regulator of this cell death process (and MCL-1 as a positive regulator for it). Furthermore, comparative analysis of secretomes from the NOXA proficient or deficient cancer cells treated by taxol reveals variations in inflammatory cytokine production including those of IL-1β and IL-18.Thus, our results show that anti-mitotic treatments are able to induce death by apoptosis and/or pyroptosis depending on BCL-2 family balance in breast cancer cells. Furthermore, NOXA/MCL-1 ratio appears to control the communication between these two types of cell death and their associated extracellular inflammatory signals in coordination with the pore-forming gasdermin GSDME.
Microglia facilitate and stabilize the response to general anesthesia
Authors: He Yang , Liu Taohui , He Quansheng , Ke Wei , Li Xiaoyu , Du Jinjin , Deng Suixin , Shu Zhenfeng , Wu Jialin , Yang Baozhi , Wang Yuqing , Mao Ying , Rao Yanxia , Shu Yousheng , Peng Bo 
Published: October 2023

AbstractGeneral anesthesia leads to a loss of consciousness and an unarousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.
A metagenomics pipeline reveals insertion sequence-driven evolution of the microbiota
Authors: Kirsch Joshua M. , Hryckowian Andrew J. , Duerkop Breck A. 
Published: October 2023

AbstractInsertion sequence (IS) elements are mobile genetic elements in bacterial genomes that support adaptation. We developed a database of IS elements coupled to a computational pipeline that identifies IS element insertions in the microbiota. We discovered that diverse IS elements insert into the genomes of intestinal bacteria regardless of human host lifestyle. These insertions target bacterial accessory genes that aid in their adaptation to unique environmental conditions. Using IS expansion inBacteroides, we show that IS activity leads to insertion “hot spots” in accessory genes. We show that IS insertions are stable and can be transferred between humans. Extreme environmental perturbations force IS elements to fall out of the microbiota and many fail to rebound following homeostasis. Our work shows that IS elements drive bacterial genome diversification within the microbiota and establishes a framework for understanding how strain level variation within the microbiota impacts human health.
A coarse-grained model of glycosaminoglycans for biomolecular simulations
Authors: Shivgan Aishwary T. , Marzinek Jan K. , Krah Alexander , Matsudaira Paul , Verma Chandra S. , Bond Peter J. 
Published: October 2023

AbstractProteoglycans contain glycosaminoglycans (GAGs), negatively charged linear polymers made of repeating disaccharide units of uronic acid and hexosamine units. They play vital roles in numerous physiological and pathological processes, particularly governing cellular communication and attachment. Depending on their sulphonation state, acetylation, and glycosidic linkages, GAGs belong to different families. The high molecular weight, heterogeneity, and flexibility of GAGs hampers their characterization at atomic resolution, but this may be circumvented via coarse-grained (CG) approaches. In this work, we report a CG model for a library of common GAG types in their isolated or proteoglycan-linked states compatible with the widely popular CG Martini forcefields (versions 2.2 and 3.0). The model reproduces conformational and thermodynamic properties for a wide variety of GAGs, as well as matching structural and binding data for selected proteoglycan test systems. The parameters developed here may thus be employed to study a range of GAG-containing biomolecular systems, benefitting from the efficiency and broad applicability of the Martini framework.
YY2/BUB3 axis-mediated SAC hyperactivity determines tumor cell fate through chromosomal instability
Authors: Hosea Rendy , Duan Wei , Meliala Ian Timothy Sembiring , Li Wenfang , Wei Mankun , Hillary Sharon , Zhao Hezhao , Miyagishi Makoto , Wu Shourong , Kasim Vivi 
Published: October 2023

AbstractSpindle assembly checkpoint (SAC) is a crucial safeguard mechanism of mitosis fidelity, which is fundamental for equal division of duplicated chromosomes to the two progeny cells. Impaired SAC can lead to chromosomal instability (CIN), a well-recognized hallmark of cancer that facilitates tumor progression; paradoxically, high CIN levels are associated with better drug sensitivity and prognosis. However, the mechanism by which CIN determines tumor cell fates and drug sensitivity remain poorly understood. In this study, using a cross-omics approach, we identified YY2 as a mitotic regulator that peaks at M phase and promotes SAC activity by positively regulating the transcriptional activity ofbudding uninhibited by benzimidazole 3(BUB3), a component of SAC. While inducing CIN, YY2/SAC activity defect enhanced mitosis and tumor growth, whereas YY2/SAC hyperactivation, as a result ofYY2overexpression, triggered mitotic delay and growth suppression. Furthermore, we revealed that excessive CIN, caused by eitherYY2overexpression or further inhibiting SAC activity inYY2-knocked out cells, leads to higher cell death rates. However, residual tumor cells that survived DNA damage-based therapy had moderate CIN and increased drug resistance; meanwhileYY2overexpression in these cells sensitizes them to DNA-damage agents. Hence, this study provides insights into the regulatory mechanism of SAC activity as well as the role of YY2/BUB3 axis, SAC activity, and CIN levels in determining tumor cell fate. Furthermore, this study also links up tumor cells drug resistance with moderate CIN, and suggest a novel anti-tumor therapeutic strategy that combines SAC activity modulators and DNA-damage agents.SignificanceThis study identifies the novel role of YY2/BUB3 axis as a SAC modulator, as well as emphasizing the role of YY2-mediated SAC activity and CIN levels in determining tumor cell fates.
Genetic Association ofCYP1A2Gene Variant (rs762551) with Caffeine Induced-Hypertension Susceptibility and Cytochrome P450 1A2 Protein Analyses
Authors: Amjad Gulsher , Saif Rashid , Hussain Mehnaz Ghulam 
Published: October 2023

AbstractHigh blood pressure is one of the most common illnesses affecting the Pakistani population due to, but not limited to, dietary habits, sedentary lifestyle and socio-economic aspects which have devastating effects on human health and general well-being. Caffeine is metabolized by CYP1A2 which results in lowered blood pressure while its retention in case of low metabolism may lead to hypertension. This phenomenon occurs because caffeine and its metabolites block A1 receptors in the kidney lowering the function of adenosine in blood pressure regulation. Current research aimed to demonstrate the genetic association ofCYP1A2gene variant 15:74749576C>A (C allele lowering CYP1A2 activity) within caffeine induced hypertensive individuals of Pakistani origin using ARMS-PCR. This pilot scale study revealed that overall, 8%, 56% and 36% sampled population (n=50) is homozygous wild-type (C/C), heterozygous (C/A) and homozygous mutant (A/A) respectively. Similarly, alternative allele frequency is 0.28 and 0.48 in cases and controls. Chi-square (χ2) association test using PLINK data analysis toolset was applied which showed significant results of χ2(2,N= 50) = 4.244,p= 0.039. Hardy Weinberg Equilibrium analysis was also applied which establishes that sampled population is obeying the principle withp-valueof 0.241. Moreover, odds-ratio depicts that the mutant allele is 0.42 times less prevalent in cases vs. controls. A few bioinformatics tools were employed e.g., ProtParam, PsiPred, PDB-RCSB, Motif finder, CTU-TMHMM-2.0, ScanProsite, GPS PAIL2.0, PRmePRed, NetOGlyc4.0, NetPhos3, SIFT analysis and STRING database in order to predict physicochemical properties, secondary structure, 3-dimensional structure, conserved motifs, transmembrane structure, post-translational modifications, protein variants impact on its function and protein-protein interactions respectively. The current endeavor attempted to provide the genetic architecture of the aforementioned variant in this case-control study in Pakistani individuals, which can pave paths of preventive medicine initiatives through genetic counsel of the masses.
Multiunit frontal eye field activity codes the visuomotor transformation, but not gaze prediction or target memory, in a delayed saccade task
Authors: Seo Serah , Bharmauria Vishal , Schütz Adrian , Yan Xiaogang , Wang Hongying , Crawford J. Douglas 
Published: October 2023

ABSTRACTSingle-unit (SU) activity − action potentials isolated from one neuron — has traditionally been employed to relate neuronal activity to behavior. However, recent investigations have shown that multi-unit (MU) activity − ensemble neural activity recorded within the vicinity of one microelectrode − may also contain accurate estimations of task-related neural population dynamics. Here, using a well-established model-fitting approach, we compared the spatial codes of SU response fields with corresponding MU response fields recorded from the frontal eye fields (FEF) in head-unrestrained monkeys (Macaca mulatta) during a memory-guided saccade task. We focused on characterizing the visuomotor transformation from Target-in-Eye coordinates to future Gaze-in-Eye coordinates (Sajad et al., 2015). Most SUvisualresponse fields coded targets (with some predicting Gaze), whereas the MU population only coded targets. Most SUmotorresponses coded Gaze, but many still retained a target code. In contrast, MU motor activity predominantly coded Gaze with very little target coding. Finally, both SU and MU populations showed a progressive transition through intermediate ‘Target-to-Gaze’ codes during the delay period, but the MU activity showed a ‘smoother’ transition. These results confirm the theoretical and practical potential of MU activity recordings as a biomarker for fundamental sensorimotor transformations (e.g., Target-to-Gaze coding in the oculomotor system), while also highlighting the importance of SU activity for coding more cognitive (e.g., predictive / memory) aspects of sensorimotor behavior.SIGNIFICANCE STATEMENTMulti-unit recordings (undifferentiated signals from several neurons) are relatively easy to record and provide a simplified estimate of neural dynamics, but it is not clear which single-unit signals are retained, amplified, or lost. Here, we compared single-/multi-unit activity from a well-defined structure (the frontal eye fields) and behavior (memory-delay saccade task), tracking their spatial codes through time. The progressive transformation from target to gaze coding observed in single-unit activity was retained in multi-unit activity, but gaze prediction (in the visual response) and target memory (in the motor response) were lost. This suggests that multi-unit activity provides an excellent biomarker for healthy sensorimotor transformations, at the cost of missing more subtle cognitive signals.
Graphite: painting genomes using a colored De Bruijn graph
Authors: Beeloo Rick , Zomer Aldert L. , Dutilh Bas E. 
Published: October 2023

AbstractThe recent growth of microbial sequence data allows comparisons at unprecedented scales, enabling tracking of strains, mobile genetic elements, or genes. Querying a genome against a large reference database can easily yield thousands of matches that are tedious to interpret and pose computational challenges. We developed Graphite that uses a colored De Bruijn graph (cDBG) to paint query genomes, selecting the local best matches along the full query length. By focusing on the closest genomic match of each query region, Graphite reduces the number of matches while providing promising leads for genomic forensics. When applied to hundreds ofCampylobactergenomes we found extensive gene sharing, including a previously undetectedC. coliplasmid that matched aC. jejunichromosome. Together, genome painting using cDBGs as enabled by Graphite, can reveal new biological phenomena by mitigating computational hurdles. Graphite is implemented in Julia, available athttps://github.com/MGXlab/Graphite.