bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the causal relationship between sepsis and autoimmune: a mendelian randomization study
Authors: Wang Ziyi , Guo Zhe , Wang Xuesong , Chen Feng , Wang Ziwen , Wang Zhong 
Published: October 2023

Abstract

Object
Numerous epidemiological studies have identified a potential link between sepsis and a variety of autoimmune disorders. The primary objective of this study is to delve deeper into this connection, investigating the potential causal relationship between sepsis and autoimmune disorders through the application of Mendelian Randomization (MR).

Methods
To assess the potential genetic impact on sepsis risk relating to susceptibility towards immune-related outcomes, we utilized summary data from the largest European genome-wide association studies (GWAS) on these conditions using a two-sample Mendelian randomization (MR) framework. Single nucleotide polymorphisms (SNPs)—which had strong associations with the 9 traits—were extracted from the GWAS and examined their effects in an extensive European sepsis GWAS (486,484 cases and 474,841 controls). We employed inverse-variance weighted (IVW) MR, Weighted median, and MR Egger for analyses, supplementing these with sensitivity analyses and assessing level pleiotropy using MR methodologies. We also executed a reverse MR analysis to test sepsis' causal effects on the designated autoimmune traits.

Results
With primary sclerosing cholangitis (PSC) being the exception, our MR analysis suggests that susceptibility towards most autoimmune diseases doesn't affect sepsis risks. The reverse MR analysis didn't validate any influence of sepsis susceptibility over other autoimmune diseases. Our primary IVW MR analysis outcomes found general confirmation through our sensitivity MR examinations. Variance in the exposures, as dictated by the SNP sets used as MR instruments, ranged between 4.88 × 10−5 to 0.005.

Conclusion
Our MR research, centered on a European population, doesn't validate a correlation between susceptibility to the majority of autoimmune disorders and sepsis risk. Associations discerned in epidemiological studies may owe partly to shared biological or environmental confounders. The risk susceptibility for PSC does relate to sepsis risk, opening doors for personalized precision treatments in the future.
OpenNucleome for high resolution nuclear structural and dynamical modeling
Authors: Lao Zhuohan , Kamat Kartik , Jiang Zhongling , Zhang Bin 
Published: October 2023

AbstractThe intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing and microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles in interpreting experimental observations by reconstructing high-resolution structural ensembles and uncovering organization principles. However, the absence of standardized modeling tools poses challenges for furthering nuclear investigations. We present OpenNucleome—an open-source software designed for conducting GPU-accelerated molecular dynamics simulations of the human nucleus. OpenNucleome offers particle-based representations of chromosomes at a resolution of 100 KB, encompassing nuclear lamina, nucleoli, and speckles. This software furnishes highly accurate structural models of nuclear architecture, affording the means for dynamic simulations of condensate formation, fusion, and exploration of non-equilibrium effects. We applied OpenNucleome to uncover the mechanisms driving the emergence of “fixed points” within the nucleus—signifying genomic loci robustly anchored in proximity to specific nuclear bodies for functional purposes. This anchoring remains resilient even amidst significant fluctuations in chromosome radial positions and nuclear shapes within individual cells. Our findings lend support to a nuclear zoning model that elucidates genome functionality. We anticipate OpenNucleome to serve as a valuable tool for nuclear investigations, streamlining mechanistic explorations and enhancing the interpretation of experimental observations.
SOCfinder: a genomic tool for identifying cooperative genes in bacteria
Authors: Belcher Laurence J. , Dewar Anna E. , Hao Chunhui , Katz Zohar , Ghoul Melanie , West Stuart A. 
Published: October 2023

AbstractBacteria cooperate by working collaboratively to defend their colonies, share nutrients, and resist antibiotics. Nevertheless, our understanding of these remarkable behaviours primarily comes from studying a few well-characterized species. Consequently, there is a significant gap in our understanding of microbial cooperation, particularly in natural environments. To address this gap, we can use bioinformatic tools to identify cooperative traits and their underlying genes across diverse species. Existing tools address this challenge through two approaches. One approach is to identify genes that encode extracellular proteins, which can provide benefits to neighbouring cells. An alternative approach is to predict gene function using annotation tools. However, these tools have several limitations. Not all extracellular proteins are cooperative, and not all cooperative behaviours are controlled by extracellular proteins. Furthermore, existing functional annotation methods frequently miss known cooperative genes. Here, we introduce SOCfinder as a new tool to find cooperative genes in bacterial genomes. SOCfinder combines information from several methods, considering if a gene is likely to (1) code for an extracellular protein, (2) have a cooperative functional annotation, or (3) be part of the biosynthesis of a cooperative secondary metabolite. We use data on two extensively-studied species (P. aeruginosa&B. subtilis) to show that SOCfinder is better at finding known cooperative genes than existing tools. We also use theory from population genetics to identify a signature of kin selection in SOCfinder cooperative genes, which is lacking in genes identified by existing tools. SOCfinder opens up a number of exciting directions for future research, and is available to download fromhttps://github.com/lauriebelch/SOCfinder.Data SummaryAll code and associated files are available athttps://github.com/lauriebelch/SOCfinder.Impact StatementBacteria cooperate by secreting many molecules outside the cell, where they can provide benefits to other cells. While we know much about how bacteria cooperate in the lab, we know much less about bacterial cooperation in nature. Is cooperation equally important in all species? Are all cooperations equally vulnerable to cheating? To answer these questions, we need a way of identifying cooperative genes across a wide range of genomes. Here, we provide such a method – which we name SOCfinder. SOCfinder allows users to find cooperative genes in any bacterial genome. SOCfinder opens up a number of exciting directions for future research. It will allow detailed studies of non-model species, as well as broad comparative studies across species. These studies will allow cooperation in the wild to be studied in new ways.
Evaluating flash freezing for preservation of rat abdominal aorta for delayed biomechanical characterization
Authors: van der Laan Koen W.F. , Reesink Koen D. , Lambrichts Sara , Bitsch Nicole J.J.E. , van der Taelen Laura , Foulquier Sébastien , Delhaas Tammo , Spronck Bart , Giudici Alessandro 
Published: October 2023

ABSTRACTMost studies investigating arterial stiffening use animal rather than human arteries. This is because human tissue becomes available in small amounts and at irregular times, which complicates planning of experimental work. Suitable tissue preservation methods for delayed biomechanical testing prevents the need for testing fresh tissue and alleviates some of the logistical challenges of humanex vivostudies. Therefore, the present study aimed to investigate whether the existing method of flash freezing and subsequent cryostorage provides is suitable for delaying the characterization of arterial biomechanics. Fresh and flash frozen abdominal aortas (n=16 and 14, respectively) were quasi- statically and dynamically tested using a biaxial testing set-up with dynamic pressurization capabilities. The acquired biomechanical data was modeled using a constituent-based quasi-linear viscoelastic modeling framework, deriving directional stiffness parameters, individual constituent biomechanical contributions, and viscoelastic stiffening under dynamic pressurization conditions. Flash freezing reduced arterial wall thickness, increased circumferential stiffness, as well as reduced viscoelastic stiffening at higher pressures. These findings reflected those in the modeled contribution of collagen to arterial biomechanics, showing increased collagen load bearing at higher pressures. However, despite the above mentioned detectable changes, flash freezing did not alter the mechanical relation between elastin and collagen, maintaining a non-linear response to pressurization and stretch. Flash freezing may thus be suitable for studies requiring delayed characterization of passive arterial biomechanics, assuming care is taken to ascert that the impact of flash freezing on study groups can be approached as a systematic error.
Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma
Authors: Cheng Xing , An Jing , Lou Jitong , Gu Qisheng , Ding Weimin , Droby Gaith , Wang Yilin , Wang Chenghao , Gao Yanzhe , Shelton Abigail , Satterlee Andrew Benson , Mann Breanna Elizabeth , Hsiao Yun-Chung , Liu Chih-Wei , Liu Kun , Hingtgen Shawn , Wang Jiguang , Liu Zhaoliang , Miller Ryan , Wu Di , Vaziri Cyrus , Yang Yang 
Published: October 2023

ABSTRACTAlmost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides a new aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define novel molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.
Nucleo-cytoplasmic environment modulates spatio-temporal p53 phase separation
Authors: Datta Debalina , Navalkar Ambuja , Sakunthala Arunima , Paul Ajoy , Patel Komal , Masurkar Shalaka , Gadhe Laxmikant , Sengupta Shinjinee , Poudyal Manisha , Devi Jyoti , Sawner Ajay Singh , Kadu Pradeep , Shaw Ranjit , Pandey Satyaprakash , Mukherjee Semanti , Gahlot Nitisha , Sengupta Kundan , Maji Samir K 
Published: October 2023

AbstractPhase separation of various transcription factors and nucleic acids into biomolecular condensates is known to play an essential role in the regulation of gene expression. Here, we show that p53, a tumor suppressor and transcription factor, phase separates and forms biomolecular condensates in the nucleus of cancer cells as well as when overexpressed in the various cell lines. Although the nuclear condensates of wild-type (WT) p53 maintain their liquid state and are able to bind DNA, cancer-associated mutations not only promote misfolding but also partially rigidify the p53 condensates, which are unable to bind the DNA. Irrespective of WT or mutant form, the cytoplasmic partitioning of p53 with time also results in biomolecular condensate formation, which eventually undergoes rigidification.In vitro, WT p53 core domain (p53C) forms biomolecular condensates, which rigidify with time and the process is further promoted by cancer-associated mutations. Both RNA and non-specific DNA promote LLPS of p53C, but specific DNA promotes the dissolution of p53C condensates. The result suggests that the cellular microenvironment regulates p53 LLPS, material property and its functions.
Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation
Authors: Cho Inchul , Xu Jessie Z. , Aziz Hafsah , Lui Prudence PokWai , Xie Boyu , Tsai Pei-Hsun , Jeon Hee-Yeon , Choi Jinwook , Ali Shahnawaz , Ali Niwa 
Published: October 2023

AbstractThe maintenance of adult tissue homeostasis is dependent on the functional cross-talk between stem cells (SCs) and tissue-resident immune cells. This reciprocal relationship is also essential for tissue organogenesis during early life. The skin harbors a relatively large population of Regulatory T cells (Tregs) that accumulate within the first two weeks after birth. A functional role for early skin seeding Tregs (ETregs) during the first week of life is currently unexplored. Here, we show that skin Tregs are detected early as postnatal day 3 (P3) where they localize to hair follicle (HF) structures and enter a dynamic flux of activation marker expression. Punctual ETreg depletion from P6-P8, but not later, results in defective HF melanocyte SC (MeSC) mediated skin pigmentation in juvenile life. Transcriptomic analysis of the whole skin on P9 exhibited immediate and pronounced changes in MeSC markers and perturbation of Peroxisome proliferator-activated receptor-γ (PPARγ) target genes in the HF. Accordingly, punctual ETreg depletion combined with short-term PPARγ agonization restored skin pigmentation. Single cell profiling of P9 skin revealed that PPARγ signalling activity is preferentially diminished in the HF epithelium upon loss of ETregs. Finally, we explored changes in the single cell transcriptome of the human tissue disorder, vitiligo, characterized by a lack of melanin and consequent skin depigmentation. These analyses showed that the HF cells from lesional vitiligo skin exhibited a significant downregulation in PPARγ pathway activation, relative to heathy controls. Overall, ETregs in neonatal skin are critical for sustaining HF PPARγ signaling, which is vital for facilitating MeSC mediated skin pigmentation during postnatal development.One Sentence SummaryPPARγ pathway functions downstream of neonatal Tregs to regulate melanocyte stem cell function.
FLI1 localization to the chlamydial inclusion involves multiple mechanisms
Authors: Sturd Natalie A. , Wood Macy G. , Durham Legacy , Ouellette Scot P. , Rucks Elizabeth A. 
Published: October 2023

ABSTRACTFollowing entry into a host cell, the obligate intracellular pathogen,Chlamydia trachomatis, establishes an intracellular niche within a membrane derived vacuole called the chlamydial inclusion. The resulting inclusion membrane is modified by the pathogen and is a hybrid host-chlamydial structure. From within this intracellular niche,C. trachomatismust orchestrate numerous host-pathogen interactions to surreptitiously acquire nutrients from its host and to limit detection by the host innate immune system.C. trachomatismediates many of these interactions with the host, in part, by using a family of type III secreted membrane proteins, termed inclusion membrane proteins (Incs). Incs are embedded within the inclusion membrane, and some function to recruit host proteins to the inclusion. Two such recruited host proteins are leucinerichrepeatFlightless-1 interactingprotein 1 (LRRF1/LRRFIP1) and its binding partner Flightless 1 (FLI1/FLII). LRRF1 interacts with Inc protein Ct226. However, interactions of FLI1 with candidate Incs or with LRRF1 during infection have not been defined. We hypothesized that FLI1 recruitment to the inclusion would be dependent on LRRF1 localization. To test this hypothesis, we used siRNA targetinglrrf1orfli1,revealing that FLI1 can localize to the inclusion independently of LRRF1. Therefore, to further characterize FLI1 localization, we developed and characterized a series of CRISPRi knockdown and complementation strains inC. trachomatisserovar L2 that targetct226and co-transcribed candidate Incs,ct225andct224, to understand the mechanisms of FLI1 and LRRF1 localization to the inclusion. Our results indicate that FLI1 is recruited to the inclusion by multiple mechanisms.IMPORTANCEChlamydia trachomatisis a leading cause of both preventable infectious blindness and bacterial sexually transmitted infections worldwide. SinceC. trachomatismust grow and replicate within human host cells, it has evolved several ways of manipulating the host to establish a successful infection. As such, it is important to describe the interactions between host proteins and chlamydial proteins to understand which strategiesC. trachomatisuses to shape its intracellular environment. This study looks in detail at such interactions of two host proteins, FLI1 and LRRF1, during chlamydial infection. Importantly, the series of knockdown and complement strains developed in this study suggest these proteins have both independent and overlapping mechanisms for localization, which ultimately will dictate how these proteins function during chlamydial infection.
Bibliometric and Temporal Trend Analysis of Nipah Virus- An Emerging Zoonotic Disease: What Do We Know So Far
Authors: Singla Rajeev K. , Zhang Yingbo , Singla Shailja , Shen Bairong 
Published: October 2023

AbstractBackgroundNipah virus (Genus Henipavirus) was first detected in 1999, during the Malaysia-Singapore outbreak, and is an emerging bat-borne pathogen. It causes rare but fatal disease, with a 40-75% fatality rate, and clinically ranging from asymptomatic infection to fatal encephalitis.MethodsPublicly available literature, including preclinical and clinical studies, have been retrieved from PubMed, Scopus, and Web of Science. Bibliometric analysis was done using embedded tools of these search engines along with VOSviewer.Results601 documents from PubMed, 955 from Web of Science, and 784 from Scopus were analyzed, and we found that maximum contributions are from the USA, India, Malaysia, Australia, and Bangladesh, and in the past five years, there has been an exponential surge in the publication rate. More research and high-throughput screening are needed to explore drugs against critical targets and receptors like ephrin-B2, non-structural protein C, F protein, L protein, G glycoprotein, nucleocapsid protein, V protein, P protein, and W protein. Research for possible vaccination is underway, but the rate is not significant. Clinical studies in this direction are minimal, undermining the fatality of this lethal disease and possible outbreak.ConclusionTo our knowledge, this is the first bibliometric analysis of Nipah virus-related documents. It urgently demands expedited research in this direction before it is too late.Author SummaryNipah virus, a rare but deadly bat-borne pathogen, has gained increased attention in recent years. Our pioneering bibliometric analysis reveals a surge in research interest. This study underscores the pressing need for accelerated research on drugs and vaccines to combat this lethal disease and prevent potential outbreaks. Urgency is paramount.
Targeting CD45 by gene-edited CAR-T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning
Authors: Stepanova V.M. , Volkov D.V. , Osipova D.S. , Wang W. , Hou Y. , Pershin D.E. , Fadeeva M.S. , Malahova E.A. , Kulalovskaya E.A. , Cuicui L. , Mingfeng Z. , Zhang H. , Xie J. , Zhang D. , Mamedov I.Z. , Chernov A.S. , Telegin G.B. , Rubtsov Y.P. , Gabibov A.G. , Wu P. , Maschan M.A. , Stepanov A.V. 
Published: October 2023

AbstractHematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. The currently used nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, which limits the use of this potentially curative treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches based on antibody‒drug conjugates, naked antibodies and CAR T cells. Here, we propose a preconditioning strategy based on targeting CD45 on hematopoietic cells with CAR45 T cells. To avoid fratricide of CD45 CAR T cells, targeted genomic disruption of the CD45 gene was performed in human CD45 CAR T cells in combination with dasatinib treatment. CD45ΔCAR45 T cells showed impressive activity in terms of target cell eliminationin vitroand depletion of tumor cellsin vivoor human hematopoietic cells in humanized immunodeficient mice engrafted with human blood-derived HSCs. CD45ΔCAR45 NK cells also exhibited potent killing activity against tumor cell lines and human hematopoietic cells. Therefore, fratricide-resistant CAR45 T and NK cells have the potential to provide the benefits of full myeloablative conditioning and therapy for hematologic malignancies. Thus, we provide the proof of concept for the generation and preclinical efficacy of CAR T cells directed against CD45-expressing cells.
Xanthomonas sontii, and notXanthomonas sacchari, is the dominant, vertically transmitted core rice seed endophyte
Authors: Rana Rekha , Patil Prabhu B. 
Published: October 2023

AbstractSeeds endophytes, particularly the abundant, core and vertically transmitted species, are major areas of focus in the host microbiome studies. Apart from being the first members to colonize, they accompany the plant throughout its development stages and also to the next generation. In a recently published study from china, aXanthomonasspecies was reported as the keystone species that is core endophyte and vertically transmitted in rice with probiotic properties. However, the species status was wrongly reported asX. sacchari. Such report is misleading asXanthomonas sacchariis a well-known and pathogenic species of sugarcane, and the study did not include the two-probiotic non-pathogenicXanthomonasspecies from rice seeds,Xanthomonas sontiiandXanthomonas indica, that were discovered and investigated in details by our group, leading to the wrong inference. By including these species, we have correctly established the phylogenetic and taxonomic identity of keystone species asXanthomonas sontii, a non-pathogen with plant protective functions. The course correction will enable researchers to use the correct reference or lab strain ofX. sontiifor further fundamental studies and translational research towards future agriculture.