bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the bacteriophage nucleus protein interaction network
Authors: Enustun Eray , Deep Amar , Gu Yajie , Nguyen Katrina T. , Chaikeeratisak Vorrapon , Armbruster Emily , Ghassemian Majid , Villa Elizabeth , Pogliano Joe , Corbett Kevin D. 
Published: May 2023

AbstractIn the arms race between bacteria and bacteriophages (phages), some large-genome jumbo phages have evolved a protein shell that encloses their replicating genome to protect it against DNA-targeting immune factors. By segregating the genome from the host cytoplasm, however, the “phage nucleus” introduces the need to specifically transport mRNA and proteins through the nuclear shell, and to dock capsids on the shell for genome packaging. Here, we use proximity labeling and localization mapping to systematically identify proteins associated with the major nuclear shell protein chimallin (ChmA) and other distinctive structures assembled by these phages. We identify six uncharacterized nuclear shell-associated proteins, one of which directly interacts with self-assembled ChmA. The structure and protein-protein interaction network of this protein, which we term ChmB, suggests that it forms pores in the ChmA lattice that serve as docking sites for capsid genome packaging, and may also participate in mRNA and/or protein transport.
A gradual transition toward categorical representations along the visual hierarchy during working memory, but not perception
Authors: Chunharas Chaipat , Wolff Michael J. , Hettwer Meike D. , Rademaker Rosanne L. 
Published: May 2023

AbstractThe ability to stably maintain visual information over brief delays is central to healthy cognitive functioning, as is the ability to differentiate such internal representations from external inputs. One possible way to achieve both is via multiple concurrent mnemonic representations along the visual hierarchy that differ systematically from the representations of perceptual inputs. To test this possibility, we examine orientation representations along the visual hierarchy during perception and working memory. Human participants directly viewed, or held in mind, oriented grating patterns, and the similarity between fMRI activation patterns for different orientations was calculated throughout retinotopic cortex. During direct viewing of grating stimuli, similarity was relatively evenly distributed amongst all orientations, while during working memory the similarity was higher around oblique orientations. We modeled these differences in representational geometry based on the known distribution of orientation information in the natural world: The “veridical” model uses an efficient coding framework to capture hypothesized representations during visual perception. The “categorical” model assumes that different “psychological distances” between orientations result in orientation categorization relative to cardinal axes. During direct perception, the veridical model explained the data well. During working memory, the categorical model gradually gained explanatory power over the veridical model for increasingly anterior retinotopic regions. Thus, directly viewed images are represented veridically, but once visual information is no longer tethered to the sensory world there is a gradual progression to more categorical mnemonic formats along the visual hierarchy.
Centromere-specifying nucleosomes persist in aging mouse oocytes in the absence of nascent assembly
Authors: Das Arunika , Boese Katelyn G. , Tachibana Kikue , Baek Sung Hee , Lampson Michael A. , Black Ben E. 
Published: May 2023

SUMMARYCentromeres direct genetic inheritance but are not themselves genetically encoded. Instead, centromeres are defined epigenetically by the presence of a histone H3 variant, CENP-A1. In cultured somatic cells, an established paradigm of cell cycle-coupled propagation maintains centromere identity: CENP-A is partitioned between sisters during replication and replenished by new assembly, which is restricted to G1. The mammalian female germline challenges this model because of the cell cycle arrest between pre-meiotic S-phase and the subsequent G1, which can last for the entire reproductive lifespan (months to decades). New CENP-A chromatin assembly maintains centromeres during prophase I in worm and starfish oocyte2,3, suggesting that a similar process may be required for centromere inheritance in mammals. However, we show that centromere chromatin is maintained long-term independent of new assembly during the extended prophase I arrest in mouse oocytes. Conditional knockout of Mis18α, an essential component of the assembly machinery, in the female germline at the time of birth has almost no impact on centromeric CENP-A nucleosome abundance nor any detectable detriment to fertility.
Effects of age on the response to spinal cord injury: optimizing the larval zebrafish model
Authors: Walker Whitney J. , Underwood Kirsten L. , Garrett Patrick I. , Lorbacher Kathryn B. , Linch Shannon M. , Rynes Thomas P. , Sloop Chloe , Mruk Karen 
Published: May 2023

ABSTRACTZebrafish are an increasingly popular model to study regeneration after spinal cord injury (SCI). The transparency of larval zebrafish makes them ideal to study cellular processes in real time. Standardized approaches, including age at the time of injury, are not readily available making comparisons of the results with other models challenging. In this study, we systematically examined the response to spinal cord transection of larval zebrafish at three different larval ages (3-, 5-, or 7-days post fertilization (dpf)) to determine whether the developmental complexity of the larvae affects the overall response to SCI. We then used imaging and behavioral analysis to evaluate whether differences existed based on the age of injury. Injury led to increased expression of cytokines associated with the immune response; however, we found that the timing of specific inflammatory markers changed with the age of the injury. We also observed changes in glial and axonal bridging with age. Young larvae (3 dpf) were better able to regenerate axons independent of the glial bridge, unlike older larvae (7 dpf), consistent with results seen in adult zebrafish. Finally, locomotor experiments demonstrated that some swimming behavior occurs independent of glial bridge formation, further highlighting the need for standardization of this model and functional recovery assays. Overall, we found differences based on the age of transection in larval zebrafish, underlining the importance of considering age when designing experiments aimed at understanding regeneration.
Emerging Activity Patterns and Synaptogenesis in Dissociated Hippocampal Cultures
Authors: Suresh Jyothsna , Saddler Mark , Bindokas Vytas , Bhansali Anita , Pesce Lorenzo , Wang Janice , Marks Jeremy , van Drongelen Wim 
Published: May 2023

AbstractCultures of dissociated hippocampal neurons display a stereotypical development of network activity patterns within the first three weeks of maturation. During this process, network connections develop and the associated spiking patterns range from increasing levels of activity in the first two weeks to regular bursting activity in the third week of maturation. Characterization of network structure is important to examine the mechanisms underlying the emergent functional organization of neural circuits. To accomplish this, confocal microscopy techniques have been used and several automated synapse quantification algorithms based on (co)localization of synaptic structures have been proposed recently. However, these approaches suffer from the arbitrary nature of intensity thresholding and the lack of correction for random-chance colocalization. To address this problem, we developed and validated an automated synapse quantification algorithm that requires minimal operator intervention. Next, we applied our approach to quantify excitatory and inhibitory synaptogenesis using confocal images of dissociated hippocampal neuronal cultures captured at 5, 8, 14 and 20 daysin vitro, the time period associated with the development of distinct neuronal activity patterns. As expected, we found that synaptic density increased with maturation, coinciding with increasing spiking activity in the network. Interestingly, the third week of the maturation exhibited a reduction in excitatory synaptic density suggestive of synaptic pruning that coincided with the emergence of regular bursting activity in the network.
Development of in-line anoxic small-angle X-ray scattering and structural characterization of an oxygen-sensing transcriptional regulator
Authors: Illava Gabrielle , Gillilan Richard , Ando Nozomi 
Published: May 2023

AbstractOxygen-sensitive metalloenzymes are responsible for many of the most fundamental biochemical processes in nature, from the reduction of di-nitrogen in nitrogenase to the biosynthesis of photosynthetic pigments. However, biophysical characterization of such proteins under anoxic conditions can be challenging, especially at non-cryogenic temperatures. In this study, we introduce the first in-line anoxic small-angle X-ray scattering (anSAXS) system at a major national synchrotron source, featuring both batch-mode and chromatography-mode capabilities. To demonstrate chromatography-coupled anSAXS, we investigated the oligomeric interconversions of the Fumarate and Nitrate Reduction (FNR) transcription factor, which is responsible for the transcriptional response to changing oxygen conditions in the facultative anaerobeEscherichia coli. Previous work has shown that FNR contains a labile [4Fe-4S] cluster that is degraded when oxygen is present, and that this change in cluster composition leads to the dissociation of the DNA-binding dimeric form. Using anSAXS, we provide the first direct structural evidence for the oxygen-induced dissociation of theE. coliFNR dimer and its correlation with cluster composition. We further demonstrate how complex FNR-DNA interactions can be studied by investigating the promoter region of the anaerobic ribonucleotide reductase genes,nrdDG, which contains tandem FNR binding sites. By coupling SEC-anSAXS with full spectrum UV-Vis analysis, we show that the [4Fe-4S] clustercontaining dimeric form of FNR can bind to both sites in thenrdDGpromoter region. The development of in-line anSAXS greatly expands the toolbox available for the study of complex metalloproteins and provides a foundation for future expansions.
A systematic narrative review of coroners’ prevention of future deaths reports (PFDs): a potential metric for patient safety in hospitals
Authors: Bremner Benjamin T. , Heneghan Carl , Aronson Jeffrey K. , Richards Georgia C. 
Published: May 2023

AbstractPatient harm due to unsafe healthcare is widespread, potentially devastating, and often preventable. Hoping to eliminate avoidable harms, the World Health Organization (WHO) published the Global Patient Safety Action Plan in July 2021. The UK’s National Health Service relies on several measures, including “never events”, “serious incidents”, patient safety events, and coroners’ prevention of future death reports (PFDs) to monitor healthcare quality and safety. We conducted a systematic narrative review of PubMed and medRxiv on 19 February 2023 to explore the strengths and limitations of coroners’ PFDs and whether they could be a safety metric to help meet the WHO’s Global Patient Safety Action Plan. We identified 17 studies that investigated a range of PFDs, including preventable deaths involving medicines and an assessment during the COVID-19 pandemic. We found that PFDs offered important information that could support hospitals to improve patient safety and prevent deaths. However, inconsistent reporting, low response rates to PFDs, and difficulty in accessing, analysing, and monitoring PFDs limited their use and adoption as a patient safety metric for hospitals. To fulfil the potential of PFDs, a national system is required that develops guidelines, sanctions failed responses, and embeds technology to encourage the prevention of future deaths.
Bidirectional two-sample Mendelian randomization study of differential white blood cell count and schizophrenia
Authors: Leung Perry BM , Liu Zipeng , Zhong Yuanxin , Di Forti Marta , Murray Robin M , So Hon-Cheong , Sham Pak C , Lui Simon SY 
Published: May 2023

AbstractBackgroundSchizophrenia and white blood cell count (WBC) are both complex and polygenic disease/traits. Previous evidence suggested that increased WBC is associated with higher all-cause mortality, and other evidence found elevated WBC in first-episode psychosis and chronic schizophrenia patients. However, prior observational findings may be confounded by antipsychotic exposures and their effects on WBC. Mendelian randomization (MR) is a useful method to examine the directional causal relationship between schizophrenia and WBCMethodsWe performed a two-sample MR using summary statistics of the Psychiatric Genomics Consortium Schizophrenia Workgroup (N=130,644) and the Blood Cell Consortium (N=563,085). The MR methods included inverse variance weighted, ME Egger, weighted median, and MR-PRESSO, contamination mixture, and a novel approach called mixture model reciprocal causal inference (MRCI). False discovery rate was employed to correct for multiple testing.ResultsAfter correcting for horizontal pleiotropy, the MRCI method demonstrated that elevated lymphocyte count (causal effects at the liability scale=0.077; FDR adjusted p-value=0.026) and eosinophil count (causal effects at the liability scale=0.048; FDR adjusted p-value=0.026) may cause schizophrenia. The contamination mixture method showed that schizophrenia may lead to elevated neutrophil count (beta=0.011 in unit of standard deviation of mean absolute neutrophil count; FDR adjusted p-value=0.045) and reduction of eosinophil count (beta=-0.013 in unit of standard deviation of mean absolute eosinophil count; FDR adjusted p-value=0.045). Some further significant findings had been identified by conventional MR approaches and MR-PRESSO, but we interpreted those with cautious due to substantial heterogeneity and plausible pleiotropic effects identified.ConclusionThis MR study provided evidence that schizophrenia has causal relationships with altered differential WBC. Our findings support the role of WBC in influencing schizophrenia risk, and may concur with the hypothesis of neuroinflammation in schizophrenia.
Assessing the effect of zoo closure on the soundscape using multiple measures
Authors: Lewis Rebecca N , Williams Leah J , de Kort Selvino R , Gilman R Tucker 
Published: May 2023

AbstractThe zoo soundscape has a number of important implications for animal welfare, management, and conservation. However, despite its importance, the zoo soundscape is yet to be examined in depth using multiple measures. Consistent human presence can influence the zoo soundscape. However, it is difficult to determine the specific impact of human presence, as visitors are usually present during the day when animals are active. The COVID-19 lockdown in 2020 provided a unique opportunity to study zoo soundscapes in the absence of visitors. We compared the sound environment during the 2020 closure period to a comparable open period in 2019 across three zoo aviaries, examining broad band frequency measures of sound pressure levels, sound pressure levels in defined frequency bands, and acoustic indices (Acoustic Complexity Index and Normalized Difference Soundscape Index) to describe the zoo soundscape. Acoustic indices have not, to our knowledge, previously been used in the zoo setting, although they may provide a useful metric to assess sound disturbance. Therefore, we also used this natural experiment to explore how successful these measures may be in assessing disturbances in captive environments. We found a significant effect of human presence on the sound environment; aviaries were generally quieter with less low frequency noise and with a greater proportion of biotic sound during the 2020 zoo closure period. We argue that NDSI could be a useful index for determining anthropogenic disturbance in zoos, although further information on how it is influenced by additional factors, such as human speech, would be beneficial. The use of multiple measures to assess the sound environment in zoos can provide additional information beyond ‘loudness’, such as frequencies where sound energy is concentrated and characteristics of the soundscape, which could be used to better target management and mitigation.
Adaptive Pathfinding by Nucleokinesis during Amoeboid Migration
Authors: Kroll Janina , Hauschild Robert , Stefanowski Kasia , Hermann Monika D. , Merrin Jack , Shafeek Lubuna , Müller-Taubenberger Annette , Renkawitz Jörg 
Published: May 2023

AbstractMotile cells moving in multicellular organisms encounter microenvironments of locally heterogeneous mechanochemical composition. Individual compositional parameters like chemotactic signals, adhesiveness, and pore sizes are well known to be sensed by motile cells, providing individual guidance cues for cellular pathfinding. However, motile cells encounter diverse mechanochemical signals at the same time, raising the question of how cells respond to locally diverse and potentially competing signals on their migration routes. Here, we reveal that motile amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical microenvironments. Using mammalian immune cells and the amoebaDictyostelium discoideum, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step cell polarity switch and is driven by myosin II-forces, sliding the nucleus from a ‘losing’ to the ‘winning’ leading edge to re-adjust the nuclear to the cellular path. Impaired nucleokinesis distorts fast path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that motile single-cell amoebae, many immune cells, and some cancer cells utilize an amoeboid migration strategy, these results suggest that amoeboid nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.
Senescent cells in Giant Cell Arteritis have inflammatory phenotype participating in tissue injury via IL-6 dependent pathways
Authors: Veroutis D , Argyropoulou OD , Goules AV , Kambas K , Palamidas DA , Evangelou K , Havaki S , Polyzou A , Xingi E , Karatza E , Boki K , Cavazza A , Kittas C , Thanos D , Ricordi C , Marvisi C , Muratore F , Galli E , Croci S , Salvarani C , Gorgoulis VG , Tzioufas AG 
Published: May 2023

AbstractObjectivesAge is the strongest risk factor of Giant Cell Arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multi-marker algorithm in tissue artery biopsies (TABs) of GCA patients.MethodsSeventy five positive TABs from GCA patients and 22 negative from patients with Polymyalgia Rheumatica (PMR) were retrospectively retrieved and analyzed. Senescent cells and their histologic origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype (SASP) by triple co-staining. GCA or PMR artery culture supernatants were applied to primary skin fibroblasts with or without IL-6 blocking agent to explore the induction of IL-6 associated cellular senescence.ResultsSenescent cells were mainly present in GCA arteries at higher proportion compared to PMR (9.50% vs 2.66% respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts and macrophages while MMP-9 by fibroblasts only. IL-6 positive senescent cells were associated with the extension of vascular inflammation (adventitial limited disease vs transmural inflammation: 10.02% vs 4.37% respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6 blockade.ConclusionsSenescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk. These findings might suggest a potential implication in disease pathogenesis by perpetuating inflammation and affecting vascular remodeling via IL-6 dependent mechanisms.
Epithelial cells maintain memory of prior infection withStreptococcus pneumoniaethrough di-methylation of histone H3
Authors: Chevalier Christine , Chica Claudia , Matheau Justine , Connor Michael G. , Pain Adrien , Hamon Melanie A. 
Published: May 2023

AbstractEpithelial cells are the first point of contact for bacteria entering the respiratory tract.Streptococcus pneumoniaeis an obligate human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumonia. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasiveS. pneumoniaeis currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. In this study, we demonstrate thatS. pneumoniaeactively induces di-methylation of lysine 4 on histone H3 (H3K4me2), which persists for at least 9 days upon clearance of bacteria with antibiotics. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses for subsequent infection.