bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kidney Status and Events Preceding Death in Heart Failure: A Real-world Nationwide Study
Authors: Anjum Deewa Zahir , Garred Caroline Hartwell , Carlson Nicholas , Fosbol Emil , Elmegaard Mariam , Jhund Pardeep S. , McMurray John J.V. , Petrie Mark C. , Kober Lars , Schou Morten 
Published: October 2024

AbstractBackgroundChronic kidney disease (CKD) is a frequent comorbidity in heart failure (HF) patients, affecting prognosis and mortality. This study investigates the relationship between kidney function and adverse kidney events preceding death in HF patients.MethodsWe analyzed registry data of HF patients who died between 2014 and 2021, with at least one year of HF diagnosis. Adverse kidney events, including acute kidney injury (AKI) and end- stage kidney disease (ESKD), were assessed. Patients were grouped by estimated glomerular filtration rate (eGFR) one year before death: eGFR≥60, eGFR 30-59, and eGFR<30.ResultsAmong 36,435 HF patients who died, 37% had eGFR≥60, 46% had eGFR 30-59, and 17% had eGFR<30 one year before death. Median age was 81 years, and 61.2% were men. Adverse kidney events occurred in 13.1% of patients. AKI was inversely related to kidney function, affecting 6.5% (95% confidence interval 6.1-6.9) of those with eGFR≥60, 7.0% (6.6.-7.4) with eGFR 30-59, and 21.9% (20.9-22.9) with eGFR<30. ESKD occurred in 0.7%(0.6-0.9), 2.6% (2.4-2.8), and 35.5% (34.3-36.7) of patients in the respective eGFR categories. In the last three months before death, kidney function notably declined, with increased chronic kidney replacement therapy. Factors associated with higher adverse kidney events included younger age, male sex, in-hospital death, and greater frailty.ConclusionsIn HF patients, AKI and ESKD are common in the last year of life, particularly in those with lower baseline eGFR, with kidney decline accelerating in the final months.
Comprehensive identification of plasma membrane repair proteins revealed spatiotemporal cellular responses to plasma membrane damage
Authors: Yamazaki Yuta , Kono Keiko 
Published: October 2024

AbstractDamage to the plasma membrane (PM) is common in all types of cells. PM repair processes, including exocytosis and endocytosis, are not mutually exclusive; rather, they collaborate to repair the wound. However, the temporal coordination between the repair processes remains poorly understood. Here, by comprehensively identifying PM repair proteins, we resolved the temporal PM repair processes at the damage site inSaccharomyces cerevisiae. Of the 80 repair proteins identified, 72 proteins were previously unreported repair protein candidates. We showed that polarity establishment, polarized exocytosis, and clathrin-mediated endocytosis (CME) occur in a specific temporal order at the damage site. Furthermore, we showed that polarized exocytosis and CME are coupled at the damage site, delivering PM repair proteins with transmembrane domains between the growing bud site and the damage site. This study provides insights into the temporal dynamics of coordinated cellular response to PM damage.
Dengue virus replicative-form dsRNA is recognized by RIG-I and MDA5 cooperatively to activate innate immunity
Authors: Ye Sichao , Liang Yisha , Chang Yu , Lai Bailiang , Zhong Jin 
Published: October 2024

AbstractRIG-I like receptors (RLRs) are a family of cytosolic RNA sensors that sense RNA virus infection to activate innate immune response. It is generally believed that different RNA viruses are recognized by either RIG-I or MDA5, two important RLR members, depending on the nature of pathogen-associated molecular patterns (PAMPs) that are generated by RNA virus replication. Dengue virus (DENV) is an important RNA virus causing serious human diseases. Despite extensive investigations, the molecular basis of the DENV PAMP recognized by the host RLR has been poorly defined, and which RLR is involved in sensing the DENV PAMP remains controversial. Here, we demonstrated that the DENV infection-induced interferon response is dependent upon both RIG-I and MDA5, with RIG-I playing a predominant role. Next we purified the DENV PAMP RNA from the DENV-infected cells, and demonstrated that the purified DENV PAMP is viral full-length double-stranded RNA bearing 5’ppp modifications, likely representing the viral replicative-form RNA. Finally, we confirmed the nature of the DENV PAMP by reconstituting the viral replicative-form RNA fromin vitrosynthesized DENV genomic RNA. In conclusion, our work not only defined the molecular basis of the RLR-PAMP interaction during DENV infection, but also revealed the previously underappreciated recognition of the distinct moiety of same PAMP by different RLRs in innate immunity against RNA viruses.ImportanceThe molecular interaction between PAMPs and RLRs plays a crucial role in innate immune response against the RNA virus infection. To our knowledge, the exact molecular basis of the DENV PAMPs and which RLR member (RIG-I or MDA5) is involved in this recognition remain controversial. In this study, we demonstrated that the DENV PAMP is likely DENV replicative-form RNA, a double-stranded RNA. RIG-I and MDA5 can sense different moieties of this DENV PAMP to active innate immune response. Our work not only clarified which RLR and what viral PAMP are involved in innate immune sensing of DENV infection, but also revealed previously underappreciated recognition of the same PAMPs by different RLRs in innate immunity against RNA viruses.
FtsZ of wall-less bacteria forms ring-like structures
Authors: Kasai Taishi , Tahara Yohei O , Miyata Makoto , Shiomi Daisuke 
Published: October 2024

AbstractThe FtsZ protein is involved in bacterial cell division. In cell-walled bacteria, such asBacillus subtilis, FtsZ forms a ring-like structure, called the Z ring, at the cell division site and acts as a scaffold for cell wall synthesis. The inhibition of cell wall synthesis inB. subtilishas been shown to interfere with the function of the Z ring, causing a loss in cell division control.Spiroplasma, a cell wall-less bacterium, lacks most of the genes involved in cell division; however, theftsZgene remains conserved. The function ofSpiroplasma eriocheirisFtsZ (SeFtsZ) remains to be determined. In the present study, we analyzed the biochemical characteristics of SeFtsZ. Purified SeFtsZ demonstrated lower polymerization capacity and GTPase activity than FtsZ fromE. coliandB. subtilis. We also investigated the relationship between SeFtsZ and SeSepF, which anchors FtsZ to the cell membrane, and found that SeSepF did not contribute to the stability of FtsZ filaments, unlike theB. subtilisSepF. SeFtsZ and SeSepF were produced inE. coliL-forms, where cell wall synthesis was inhibited. SeFtsZ formed ring-like structures in cell wall-lessE. colicells, suggesting that SeFtsZ forms Z rings and is involved in cell division independently of cell wall synthesis.
DDX3 regulates the cap-independent translation of the Japanese encephalitis virus via its interactions with PABP1 and the untranslated regions of the viral genome
Authors: Li Chenxi , Zhang Linjie , Tang Chenyang , Chen Xuan , Shi Jing , Li Qingyu , Jiao Xue , Guo Jinyao , Wang Bin , Bu Kefan , Wahaab Abudl , Yuan Yuguo , Sun Ming-an , Li Yanhua 
Published: October 2024

AbstractThe translation of global cellular proteins is almost completely repressed in cells with flavivirus infection, while viral translation remains efficient. The mechanisms of flaviviruses evade host translational shutoff are largely unknown. Here, we identified viral elements and host factors associated with JEV evasion of host shutoff. JEV 5′UTR lacked IRES or IRES-like activity, while noncapped 5′UTR initiated translation in the presence of 3′UTR. Furthermore, the elements DB2 and sHP-SL within 3′UTR were involved in the regulation of cap-independent translation, which is conserved in the genusOrthoflavivirus. By RNA affinity purification and mass spectrometry analysis, cellular DDX3 and PABP1 were identified as key factors in regulating cap-independent translation of JEV via their interactions with DB2 and sHP-SL RNA structures. Mechanistically, we revealed that DDX3 could bind to both 5′UTR and 3′UTR of the JEV genome to establish a closed-loop architecture, recruit eIF4G/eIF4A to form the DDX3/PABP1/eIF4G/eIF4A tetrameric complex via its interaction with PABP1, thereby recruiting 43S PIC to the 5′-end of the JEV genome to start translation. Our findings demonstrated a noncanonical translation strategy employed by JEV and further revealed the regulatory roles of DDX3 and PABP1 in this mechanism. These results expand our knowledge of the translation initiation regulation in flaviviruses under the state of host translational shutoff, which provides a conserved antiviral target againstorthoflavivirus.
Pathogenic mechanisms ofPlasmodium falciparumegress unveiled by a microvascular 3D blood-brain barrier model
Authors: Piatti Livia , Batzilla Alina , Nakaki Fumio , Fleckenstein Hannah , Korbmacher François , Long Rory K.M. , Schraivogel Daniel , Hawkins John A. , Romero-Uruñuela Tais , López-Gutiérrez Borja , Sanz Silvia , Schwab Yannick , Steinmetz Lars M. , Sharpe James , Bernabeu Maria 
Published: October 2024

AbstractCerebral malaria is a severe neurovascular complication ofPlasmodium falciparumwith high mortality, even after treatment with effective antimalarials. A better understanding of pathogenic mechanisms could help future development of adjunctive therapies, yet limitations in current experimental models have hindered our knowledge of the disease. We developed a 3D blood-brain barrier model with enhanced barrier properties using primary brain endothelial cells, astrocytes and pericytes. Exposure to parasite egress products increased microvascular permeability, likely due to transcriptional downregulation of junctional and vascular development genes in endothelial cells. In addition, it increased the expression of ferroptosis markers, antigen presentation and type I interferon genes across all BBB cell types. Incubation with cytoadherent schizont-stageP. falciparum-infected erythrocytes induced a similar, but highly localized transcriptional shift, along with inter-endothelial gaps at sites of parasite egress, significantly increasing permeability. These findings provide key insights into the parasite-mediated mechanisms driving brain microvascular pathogenesis in cerebral malaria.
Simultaneous production of lipopeptide and rhamnolipid biosurfactants byPseudomonas aeruginosa: A promising blend for biosurfactant-enhanced bioremediation
Authors: del Rosario Jacoby Maria , Iustman Laura J. Raiger 
Published: October 2024

ABSTRACTOil contamination is an environmental issue worldwide, and bioremediation has emerged as a preferred strategy to address this challenge. One of the limiting factors in oil biodegradation is its bioavailability, which can be solved by the addition of tensioactive compounds. Given the increasing demand for environmentally friendly surfactants, this study aimed to obtain cell-free biosurfactant extracts as additives in surfactant enhanced remediation (SER) protocols. Diesel-degrading, surfactant-producing strains were isolated to obtain biosurfactant extracts with minimal post-production purification cost. The most promising extracts were tested for SER assays using diesel-contaminated microcosms. One of these showed a significant enhancement in diesel degradation compared with the controls. This extract was obtained from aPseudomonas aeruginosastrain and consisted of a blend of rhamnolipids and lipopeptides. This is the first work reporting the co-production of both kinds of surfactants by aP. aeruginosastrain and its potential for application in surfactant-enhanced bioremediation strategies.HIGHLIGHTSPseudomonas aeruginosaMM and ML were isolated as diesel-degrading surfactant-producing strains.P. aeruginosaMM synthesizes rhamnolipids and lipopeptides simultaneouslyThis surfactant blend enhances diesel degradation in soil microcosm assays
Temporal Prediction through Integration of Probability Distributions of Event Timings at Multiple Levels
Authors: Huang Yiyuan Teresa , Chao Zenas C. 
Published: October 2024

AbstractOur brain uses prior experience to anticipate the timing of upcoming events. This dynamical process can be modeled using a hazard function derived from the probability distribution of event timings. However, the contexts of an event can lead to various probability distributions for the same event, and it remains unclear how the brain integrates these distributions into a coherent temporal prediction. In this study, we create a local-global foreperiod paradigm consisting of a sequence of paired trials, where in each trial, participants respond to a target signal after a specified time interval (i.e. foreperiod) following a warning cue. The prediction of the target onset in the second trial can be based on the probability distribution of the second foreperiod (local level) and its conditional probability given the foreperiod in the first trial (global level). These probability distributions are then transformed into hazard functions to represent the local and global temporal predictions. Reaction times to the target signal are best explained by incorporating both local and global predictions, indicating that both levels of temporal information contribute to making predictions. We further show that electroencephalographic source signals are best reconstructed when integrating both predictions. Specifically, the local and global predictions are separately encoded in the posterior and anterior brain regions, and to achieve synergy between both predictions, a third region—particularly the right posterior cingulate area—is needed. Our study reveals brain networks that integrate multilevel temporal information, providing a comprehensive view of hierarchical predictive coding of time.
Meta-analysis: Purity of extracted human blood DNA,E. coligDNA, and plasmid using magnetic nanoparticle
Authors: Tjoa Stanley Evander Emeltan , Mudasir Mudasir , Suharyadi Edi , Daryono Budi Setiadi 
Published: October 2024

AbstractDNA extraction technology continues to evolve along with the need for a fast and simple process. The DNA extraction with magnetic nanoparticles accommodates these demands by providing a method that is safe, simple, and yet able to give good purity. The purity parameter of the extracted DNA is based on the A260/280 value. This meta-analysis aims to find variables that can affect the purity of extracted DNA using magnetic nanoparticles, based on its extraction and particle synthesis procedure. The information to be analyzed is from DNA extraction from human blood, plasmid extraction, andE. coligDNA extraction. The research begins with a systematic review to collect appropriate studies and analysis will be carried out using Minitab to find variables that affect the purity of DNA, either positive or negative. Here we show, that no variables have been found significant to the purity of the extracted DNA in both the DNA extraction procedure steps and reagents. For the magnetic nanoparticle synthesis method, for extraction ofE. coligDNA, coating agent TEOS/TiO2; CoZnFe3O4magnetic nanoparticles, and the interaction between CoZnFe3O4and TEOS are found to be variables that influence the purity of the extracted DNA based on A260/280. Hopefully, this information can be used as a development idea, either for the magnetic nanoparticle synthesis procedure or the selection of reagents and DNA extraction procedures. In addition, the results of this analysis can also be used for consideration in an in-house magnetic nanoparticle-based DNA extraction assembly.
Domain Specific AI Segmentation of IMPDH2 Rod/Ring Structures in Mouse Embryonic Stem Cells
Authors: Ball Samuel T.M. , Hennessy Meagan J. , Tan Yuhan , Hoettges Kai F. , Perkins Neil D. , Wilkinson David J. , White Michael R.H. , Zheng Yalin , Turner David A. 
Published: October 2024

AbstractBackgroundInosine monophosphate dehydrogenase 2 (IMPDH2) is an enzyme that catalyses the rate limiting step of guanine nucleotides. In mouse embryonic stem cells (ESCs) IMPDH2 is held as large multi-protein complexes known as rod-ring (RR) structures that dissociate when ESCs differentiate. Manual analysis of RR structures from confocal microscopy images, although possible, is not feasible on a large scale due to the quantity of RR structures present in each field of view. To address this analysis bottleneck, we have created a fully automatic RR image classification pipeline to segment, characterise and measure feature distributions of these structures in ESCs.ResultsWe find that this model can automatically segment images with a Dice score of over 80% for both rods and rings for in-domain images compared to expert annotation, with a slight drop to 70% for datasets out of domain. Important feature measurements derived from these segmentations show high agreement with the measurements derived from expert annotation, achieving anR2score of over 90% for counting the number of rings and rods over the dataset.ConclusionsWe have established for the first time a quantitative baseline for RR distribution in pluripotent ESCs and have made a pipeline available for training to be applied to other models in which RR remain an open topic of study.
About bacteriophage tail terminator and tail completion proteins: structure of the proximal extremity of siphophage T5 tail
Authors: Linares Romain , Breyton Cécile 
Published: October 2024

AbstractBacteriophages are viruses infecting bacteria. The vast majority of them bear a tail, allowing host recognition, cell wall perforation and DNA injection into the host cytoplasm. Using electron cryo-microscopy (cryo-EM) and single particle analysis, we determined the organisation of the tail proximal extremity of siphophage T5 that possess a long flexible tail, and solved the structure of its tail terminator protein (TrP) p142 (TrP142). It allowed to confirm the common evolutionary origin between T5 TrPp142and other known or putative TrPs from siphophages, myophages and bacterial tail-like machines, despite very poor sequence conservation. By also determining the structure of T5 tail proximal extremity after interaction with T5 bacterial receptor FhuA, we showed that no conformational changes occur in TrPp142and confirmed that the infection signal transduction is not carried by the tube itself. We also investigated the location of T5 tail completion protein (TCP) p143 (TCPp143) and showed, thanks to a combination of cryo-EM and structure prediction using Alphafold2, that it is not located at the capsid-to-tail interface as suggested by its position in the genome, but instead, very unexpectedly, on the side of T5 tail tip, and that it appears to be monomeric. Based on structure comparison with other putative TCPs predicted structures, this feature could not be shared by other TCPs. The stoichiometry of the Tape Measure Protein is also discussed.ImportanceBacteriophages, viruses infecting bacteria, are the most abundant living entities on Earth. They are present in all ecosystems where bacteria develop and are instrumental in the regulation, diversity, evolution and pathogeny of microbial populations. Moreover, with the increasing number of pathogenic strains resistant to antibiotics, virulent phages are considered as a serious alternative or complement to classical treatments. 96% of all phages present a tail that allows host recognition and safe channelling of the DNA to the host cytoplasm. We present the atomic model of the proximal extremity of siphophage T5 tail, confirming structural similarities with other phages. This structure, combined to results previously published further explored, also allowed a review and a discussion on the role and localisation of a mysterious tail protein, the Tail Completion Protein, which is known to be present in the phage tails, but that was never identified in a phage structure.
A lipid signature of BAK-driven apoptotic pore formation
Authors: Uren Rachel T. , Ritchie Matthew E. , Wong Agnes W. , Ludeman Justin P. , Uno Etsuko , Narayana Vinod K. , De Souza David P. , Sviridov Dmitri , Kluck Ruth M. 
Published: October 2024

ABSTRACTApoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken. Firstly, the lipids released during BAK-mediated pore formation were measured with targeted lipidomics, revealing enrichment of long chain polyunsaturated lysophospholipids (LPLs) in the released fraction. In contrast, the BAK protein was not released suggesting that BAK and LPLs locate to distinct microdomains. Secondly, added cholesterol not only prevented pore formation but prevented the clustering of BAK homodimers. Our data lead us to a model in which BAK clustering triggers formation of a separate microdomain rich in LPLs that can progress to lipid shedding and the opening of a lipid-lined pore. Pore stabilisation and growth may be due to BAK dimers then moving to the pore edge. Our BAK-lipid microdomain model supports the heterogeneity of BAK assemblies, and the observed lipid-release signature gives new insight into the genesis of the apoptotic pore.
Intra-manchette transport employs both microtubule and actin tracks
Authors: Judernatz Jo H. , Pañeda Laura Pérez , Kadavá Tereza , Heck Albert J. R. , Zeev-Ben-Mordehai Tzviya 
Published: October 2024

AbstractThe manchette is a transient microtubule based structure that plays a vital role in nuclear shaping during spermio-genesis. It comprises thousands of microtubules (MTs) that build a scaffold around the distal half of the nucleus. The manchette distributes proteins and vesicles during spermio-genesis in a process called intra-manchette transport (IMT). The current hypothesis is that IMT shares many similarities with intra-flagellar transport (IFT) and utilizes both MTs and filamentous actin (F-actin). However, IMT is still poorly understood as direct visualization of IMT complexes is missing, and the presence of F-actin has not been experimentally shown. Here, we use proteomics and cryogenic-electron tomography (cryo-ET) to identify and visualize IMT components. We find that F-actin is an integral part of the manchette with two different spatial organizations, namely bundles and single filaments, providing tracks for transport as well as having structural and mechanical roles. We further uncover that IMT on MTs is mediated by two distinct transport machineries: a dynein-mediated transport of soluble cargo and a dynein-independent transport for vesicles. Our results provide new insights into the manchette’s function as a transport scaffold, highlighting its significance for the polarization of spermatids during spermiogenesis.