bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human spermatogenesis leads to a reduced nuclear pore structure and function
Authors: Santos Ália dos , Knowles Oliver , Dendooven Tom , Hale Thomas , Hale Victoria L , Burt Alister , Kolata Piotr , Cannone Giuseppe , Bellini Dom , Barford David , Allegretti Matteo 
Published: October 2024

AbstractNuclear pore complexes (NPCs) are nuclear gateways which regulate the transit of molecules larger than 40kDa through a Ran-dependent transport1. The somatic human NPC scaffold consists of three stacked rings: the cytoplasmic (CR), the nucleoplasmic (NR), and the inner ring (IR), which define a central channel approximately 55nm wide2.Although many studies have investigated human NPC architecture3, it remains largely unknown how the NPC accommodates the different functions of non-somatic cells.Here, we reveal thein-cellarchitecture of the human sperm NPC. We show that it exhibits a central channel less than 40nm-wide, outlined exclusively by the IR. This structural alteration is accompanied by a six-fold reduction in nuclear diffusion rate and mis-localization of Ran-dependent transport components. Additionally, we identify a network of septin filaments interconnecting NPCs within the inter-membrane space of the nuclear envelope (NE), suggesting a potential mechanical role in channel constriction. Furthermore, our human tissue imaging data indicate meiosis as a pivotal differentiation stage driving architectural changes to the NPC.Given the critical role of the IR for successful spermatogenesis4,5, our work offers important insight into this fundamental biological process. Our study also demonstrates the power of an integrative approach by combining electron-cryo- tomography, super-resolution-light-microscopy and biochemical analysis, to elucidate macromolecular structure-function relations in human physiological contexts.
Neural correlates of co-players’ identity and reputation processing on cooperation in the public goods game
Authors: Sampaio Waldir M. , Pantaleão Fernanda Naomi , de Souza Beatriz , Freitas Ana Luisa , Boggio Paulo S. 
Published: October 2024

AbstractThis study investigates the neural correlates of identity and reputation processing in cooperative decision-making during the Public Goods Game (PGG). Using functional near-infrared spectroscopy (fNIRS), we examined how different types of social information—co-player facial photos, reputational scores, and a combination of both—influence activity in the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). Our findings suggest that the dlPFC is crucial for integrating reputational information, reflecting its role in cognitive control and modulation of expectations during cooperative interactions. The vmPFC, on the other hand, is involved in attributing value to the cooperative decision by synthesizing identity and reputation cues. Reputation alone elicited greater dlPFC activity, highlighting the cognitive demands of evaluating past behaviors. When both identity and reputation information were presented, vmPFC activity increased, indicating greater value processing. These results demonstrate the distinct but complementary roles of the dlPFC and vmPFC in processing social cues during cooperative decision-making.
Rational Design of Enhanced Nme2Cas9 and Nme2SmuCas9 Nucleases and Base Editors
Authors: Bamidele Nathan , Ansodaria Aditya , Chen Zexiang , Cheng Haoyang , Panwala Rebecca , Jazbec Eva , Sontheimer Erik J. 
Published: October 2024

AbstractCRISPR-Cas genome editing tools enable precise, RNA-guided modification of genomes within living cells. The most clinically advanced genome editors are Cas9 nucleases, but many nuclease technologies provide only limited control over genome editing outcomes. Adenine base editors (ABEs) and cytosine base editors (CBEs) enable precise and efficient nucleotide conversions of A:T-to-G:C and C:G-to-T:A base pairs, respectively. Therapeutic use of base editors (BEs) provides an avenue to correct approximately 30% of human pathogenic variants. Nonetheless, factors such as protospacer adjacent motif (PAM) availability, accuracy, product purity, and delivery limit the full therapeutic potential of BEs. We previously developed Nme2Cas9 and its BE derivatives, including ABEs compatible with single adeno-associated virus (AAV) vector delivery, in part to enable editing near N4CC PAMs. Further engineering yielded domain-inlaid BEs with enhanced activity, as well as Nme2Cas9/SmuCas9 chimeras that target single-cytidine (N4C) PAMs. Here we further enhance Nme2Cas9 and Nme2SmuCas9 editing effectors for improved efficiency and vector compatibility through site-directed mutagenesis and deaminase linker optimization. Finally, we define the editing and specificity profiles of the resulting variants by using paired guide-target libraries.
A Vertically and Horizontally Transmitted RNA Virus Facilitates Egg Hatching of a Parasitoid Wasp
Authors: Izraeli Y. , Wodowski G. , Mozes-Daube N. , Varaldi J. , Zchori-Fein E. , Chiel E. 
Published: October 2024

AbstractInformation on the impacts of RNA viruses inhabiting insect hosts is scarce. Here, we studied the effects of a recently described RNA virus, termed AnvRV, on its host, the parasitoid waspAnagyrus vladimiri(Hymenoptera: Encyrtidae), an important natural enemy of mealybug pests. AnvRV was found to be maternally transmitted with very high fidelity but not paternally. Additionally, AnvRV was horizontally transferred at an efficiency of 23% from infected to uninfected wasp larvae that develop together inside the same mealybug host (superparasitism). To test the effects of AnvRV onA. vladimiri, the virus horizontal transmission was utilized to establish AnvRV-infected (RV+) and uninfected (RV-) isogenic wasp lines, a method rarely applied and novel to RNA virus-parasitoid systems. Longevity, developmental time, sex ratio, and fecundity of RV+and RV-A. vladimiriwere very similar. Nonetheless, the egg hatching rate of RV+wasps was markedly and significantly higher than that of RV-wasps, especially in hosts that were not superparasitized. Additionally, less encapsulation marks (the main form of mealybug immunity) were found around RV+eggs inside parasitized mealybug hosts. Taken together, the data suggest that AnvRV is affecting the mealybugs’ physiology in a way that improves first stages of wasps’ development. These findings present a rare example of interaction between an RNA virus and a parasitoid and may provide a tool for the improvement of biological control efforts.
Electrostatic interactions define nacubactam potency against OXA-48-like β-lactamases
Authors: Hoff Joseph F. , Goudar Kirsty E. , Beer Michael , Hinchliffe Philip , Shaw John M. , Tooke Catherine L. , Takebayashi Yuiko , Mulholland Adrian J. , Schofield Christopher J. , Spencer James 
Published: October 2024

AbstractCarbapenemases, β-lactamases hydrolysing carbapenem antibiotics, severely challenge treatment of multi-drug resistant bacterial infections. OXA-48 is among the most widely disseminated carbapenemases inEnterobacterales, consequently new treatment options for OXA-48 producers are urgently required. Development of diazabicyclooctane (DBO) inhibitors to overcome β-lactamase-mediated resistance is one attractive option, due to their efficacy against a wide range of β-lactamases. The DBO avibactam is already licensed for clinical use, with the related compound nacubactam currently in phase III trials for carbapenem-resistant infections. Here we investigate the activities of avibactam and nacubactam towards OXA-48 and two variants, OXA-163 and OXA-405, that contain deletions in the β5 - β6 loop adjacent to the active site and show modified activity towards different β-lactam classes. Compared to avibactam, nacubactam is c. 80-fold less potent towards OXA-48, but this difference is reduced in OXA-163 and OXA-405. Crystal structures of the respective avibactam and nacubactam complexes, and molecular dynamics simulations based upon these, reveal residue Arg214 on the OXA-48 β5 - β6 active-site loop to be electrostatically repelled by nacubactam, but not avibactam, binding. This increases flexibility of the OXA-48 β5 – β6 loop, as well as neighbouring active site loops, in simulations of the OXA-48:nacubactam, compared to the avibactam, complex. Such effects are not observed in simulations of the respective complexes of OXA-163 and OXA-405, which lack Arg214. These data indicate that interactions with Arg214 can determine DBO potency towards OXA-48-like enzymes, and suggest that sequence variation in this β-lactamase family affects reactivity towards inhibitors as well as β-lactam substrates.
Neurons and astrocytes have distinct organelle signatures and responses to stress
Authors: Rhoads Shannon N. , Dong Weizhen , Hsu Chih-Hsuan , Mfulama Ngudiankama R. , Ragusa Joey V. , Ye Michael , Henrie Andy , Zanellati Maria Clara , Diering Graham H. , Cohen Todd J. , Cohen Sarah 
Published: October 2024

SummaryNeurons and astrocytes play critical yet divergent roles in brain physiology and neurological conditions. Intracellular organelles are integral to cellular function. However, an in-depth characterization of organelles in live brain cells has not been performed. Here, we used multispectral imaging to simultaneously visualize six organelles – endoplasmic reticulum (ER), lysosomes, mitochondria, peroxisomes, Golgi, and lipid droplets – in live primary rodent neurons and astrocytes. We generated a dataset of 173 Z-stack and 99 time-lapse images accompanied by quantitative analysis of 1418 metrics (the “organelle signature”). Comparative analysis revealed clear cell-type specificity in organelle morphology and interactions. Neurons were characterized by prominent mitochondrial composition and interactions, while astrocytes contained more lysosomes and lipid droplet interactions. Additionally, neurons displayed a more robust organelle response than astrocytes to acute oxidative or ER stress. Our data provide a systems-level characterization of neuron and astrocyte organelles that can be a reference for understanding cell- type-specific physiology and disease.
A dynamic 3D polymer model of theEscherichia colichromosome driven by data from optical pooled screening
Authors: Schirman Dvir , Gras Konrad , Kandavalli Vinodh , Larsson Jimmy , Fange David , Elf Johan 
Published: October 2024

AbstractThe DNA of bacterial cells is organized in a highly dynamic chromosome structure. To guarantee its propagation, the chromosome must replicate, segregate, and accommodate other biological processes like gene expression. Therefore, to understand the causal relationship between chromosome organization and biological function, it is essential to follow chromosome dynamics. Live-cell imaging of fluorescent labels allows the tracking of specific genomic locations, but the current imaging-based approaches to study bacterial chromosome organization over the cell cycle are limited in their throughput. Even with multicolor fluorescent locus labeling, the genomic resolution is insufficient to gain insights about the whole chromosome structure from a single experiment. Although sequencing-based methods like chromosome conformation capture provide high genomic coverage, they can only be done in bulk, providing an averaged static view of the chromosome structure. In this study, we address these limitations and investigate the bacterial chromosome organization by imaging fluorescently labeled loci in a library ofEscherichia colistrains, following the 3D locations of 68 different loci in live cells in a single experiment. The resulting location distributions along the cell’s longitudinal and radial axes are used to inform a dynamic polymer model of the chromosome over the cell cycle. We show a global reorganization of theE. colichromosome, at both the longitudinal and radial axes. Our model reproduces the known chromosomal architecture of four macrodomains and demonstrates how these domains form dynamically over the cell cycle.
Superior colliculus peri-saccadic field potentials are dominated by a visual sensory preference for the upper visual field
Authors: Hafed Ziad M. 
Published: October 2024

AbstractThe primate superior colliculus (SC) plays important sensory, cognitive, and motor processing roles. Among its properties, the SC has clear visual field asymmetries: visual responses are stronger in the upper visual field representation, whereas saccade-related motor bursts are weaker. Here, I asked whether peri-saccadic SC network activity can still reflect the SC’s visual sensitivity asymmetry, thus supporting recent evidence of sensory-related signals embedded within the SC’s motor bursts. I analyzed collicular peri-saccadic local field potential (LFP) modulations and found them to be much stronger in the upper visual field, despite the weaker motor bursts. This effect persisted even with saccades towards a blank, suggesting an importance of visual field location. I also found that engaging working memory during saccade preparation differentially modulated the SC’s LFP’s, again with a dichotomous upper/lower visual field asymmetry. I conclude that the SC network possesses a clear sensory signal at the time of saccade generation.
Astrocyte transcriptomic analysis identifies glypican 5 downregulation as a contributor to synaptic dysfunction in Alzheimer’s disease models
Authors: Salas Isabel H. , Paumier Adrien , Tao Tao , Derevyanko Aksinya , Switzler Corey , Burgado Jillybeth , Movsesian Melia , Metanat Setareh , Dawoodtabar Trinity , Asbell Quinn , Fassihi Arash , Allen Nicola J. 
Published: October 2024

ABSTRACTSynaptic dysfunction is an early feature in Alzheimer’s disease (AD) and correlates with cognitive decline. Astrocytes are essential regulators of synapses, impacting synapse formation, maturation, elimination and function. To understand if synapse-supportive functions of astrocytes are altered in AD, we used astrocyte BacTRAP mice to generate a comprehensive dataset of hippocampal astrocyte transcriptional alterations in two mouse models of Alzheimer’s pathology (APPswe/PS1dE9 and Tau P301S), characterizing sex and age-dependent changes. We found that astrocytes from both models downregulate genes important for synapse regulation and function such as the synapse-maturation factor Glypican 5. This transcriptional signature is shared with human post-mortem AD patients. Manipulating a key component of this signature byin vivooverexpression of Glypican 5 in astrocytes is sufficient to prevent early synaptic dysfunction and improve spatial learning in APPswe/PS1dE9 mice. These findings open new avenues to target astrocytic factors to mitigate AD synaptic dysfunction.
Elevated temperature during rearing diminishes swimming and disturbs the metabolism of yellow perch larvae
Authors: Easwaramoorthy Mellissa , Thompson William Andrew , Fraz Shamaila , Nederveen Joshua , Hartenstein Peyton , Laframboise Lisa , Manzon Richard G. , Somers Christopher M. , Wilson Joanna Y. 
Published: October 2024

AbstractTemperate waters, such as the Great Lakes, are predicted to increase by 1°C every decade. Poikilothermic fish thermoregulate behaviourally, moving to more suitable thermal environments. Embryos are incapable of locomotion and may be exposed to non-optimal temperatures during development. Increased temperature alters the normal development of the yellow perch (Perca flavescens),however, whether altered incubation temperature influences the development of metabolism and function in these fish remains unknown. We hypothesized that increased embryonic incubation temperature would disturb cardiac and metabolic function and the behaviour of yellow perch larvae. We reared yellow perch embryos at 12°C, 15°C, or 18°C until hatching; after hatching, the temperature was raised to a common garden 18°C, their preferred post-hatch temperature. We assessed exploratory behaviour, metabolism (oxygen consumption), and cardiac performance throughout early development. At hatch, 12°C fish exhibited the greatest swimming activity, with 18°C fish consuming the least oxygen and possibly experiencing mitochondrial dysfunction. Cardiac development was more advanced at hatch in 18°C fish. Yet, warmer incubated fish had diminished movement and increased oxygen consumption at 20 days post-hatch, demonstrating long-term disruptions of increased temperature in the embryonic environment. Overall, elevations in rearing temperature may cause metabolic dysfunction and behavioural alterations, potentially impacting the survival of yellow perch.
CFC-seq: identification of full-length capped RNAs unveil enhancer-derived transcription
Authors: Yip Chi Wai , Parr Callum , Takahashi Hazuki , Yasuzawa Kayoko , Valentine Matthew , Nishiyori-Sueki Hiromi , Ugolini Camilla , Ranzani Valeria , Murata Mitsuyoshi , Kato Masaki , Kang Wenjing , Yip Wing Hin , Shibayama Youtaro , Sim Andre Darah , Chen Ying , Shu Xufeng , Moody Jonathan , Umarov Ramzan , Chang Jen-Chien , Pandolfini Luca , Kawashima Tsugumi , Tagami Michihira , Nobusada Tomoe , Kouno Tsukasa , Gonzale Carlos Alfonso , Albanese Roberto , Dossena Francesco , Haberman Nejc , Ozaki Kokoro , Kasukawa Takeya , Lenhard Boris , Frith Martin , Bodega Beatrice , Nicassio Francesco , Calviello Lorenzo , Bienko Magda , Legnini Ivano , Hilgers Valérie , Gustincich Stefano , Göke Jonathan , Lecellier Charles-Henri , Shin Jay W. , Hon Chung-Chau , Carninci Piero 
Published: October 2024

AbstractLong-read sequencing has emerged as a powerful tool for uncovering novel transcripts and genes. However, existing protocols often lack confidence in identifying the transcription start site (TSS) and fail to capture non-poly(A) RNA, thereby limiting the discovery of novel genes, particularly long non-coding RNAs (lncRNAs). In this study, we introduce Cap-trap full-length cDNA sequencing (CFC-seq), a comprehensive protocol that combines Cap-trapping and poly(A)-tailing with Oxford Nanopore sequencing. This protocol enables precise identification of TSSs and full-length transcripts. Applying CFC-seq to twoin vitrodifferentiation time courses resulted in approximately 236 million mappable reads. The transcript Start-site Aware Long-read Assembler (SALA) was developed forde novoassembling the transcript models, leading to the identification of 39,425 confident novel genes. Using this dataset, enhancer-derived ncRNAs were re-defined with longer length and more splicing activity, which were correlated with enhancer structure. Compared to enhancers with CpG islands, TATA box enhancers were shown to be more cell type specific with fewer chromatin interaction but produced longer and more stable polyadenylated RNA. A significant proportion of these TATA box-derived eRNAs originated from LTR transposable elements. Overall, this study systematically annotated ∼24,000 novel eRNA genes and correlated their transcription properties with enhancer structure.HighlightsFrom 236 million long-reads, CFC-seq identified 39,425 novel genes with genuine TSS support. These include ∼24,000 eRNA genes.SALA, a long-read assembler, was developed to facilitate genuine TSS incorporation.Compared to TATA box enhancers, CGI enhancers are more ubiquitous, enriched with repressive histone mark, with more chromatin connection and are enriched in 2D and super enhancer.eRNAs derived from TATA box are longer, more stable, frequently spliced with high splicing efficiency, frequently polyadenylated, and are enriched with LTR retrotransposons.The 3’end of non-poly(A) eRNA reveal the cleavage position depleted of secondary structure.
Lipid Disbalance Affects Neuronal Dendrite Growth and Maintenance in a Human Ceramide Synthase Disease Model
Authors: Ziegler Anna B , Wesselmann Cedrik , Beckschäfer Konstantin , Wulf Anna-Lena , Dhiman Neena , Soba Peter , Thiele Christoph , Bauer Reinhard , Tavosanis Gaia 
Published: October 2024

SummaryThe brain is susceptible to disturbances in lipid metabolism. Among the rare, genetically-linked epilepsies Progressive Myoclonic Epilepsy Type 8 (PME8), associated with the loss of Ceramide Synthase (CerS) activity, causes epileptic symptoms accompanied by neurodegenerative traits. We show that expression of a disease-causing cerSallele inDrosophilasensory neurons yielded developmental and degenerative dendrite loss. IncerSmutants, C18-C24 ceramides and membrane-forming complex sphingolipids, into which ceramides are converted, were reduced. At the same time bioactive signaling lipids including (dh)Sphingosine-1-P, deriving from the CerS substrate, were increased. To clarifying the etiology of PME8, we thus performedin vivoexperiments to cell-autonomously rescue the individual metabolic alterations. We report that restoring specific long-chain ceramides while in parallel decreasing (dh)Sphingosine-1-P fully rescues thecerSmutant phenotype. Thus, despite the complex metabolic alterations, our data provide essential information about the metabolic origin of PME8 and delineate a potential therapy.
Relativistic diffusion model for hadron production in
p
-Pb collisions at energies available at the CERN Large Hadron Collider
Authors: Schulz Philipp , Wolschin Georg 
Published: October 2024

We investigate charged-hadron production in relativistic heavy-ion collisions of asymmetric systems within a nonequilibrium-statistical framework. Calculated centrality-dependent pseudorapidity distributions for p-Pb collisions at sNN=5.02 and 8.16 TeV are compared with data from the Large Hadron Collider. Our approach combines a relativistic diffusion model with formulations based on quantum chromodynamics while utilizing numerical solutions of a Fokker-Planck equation to account for the shift and broadening of the fragmentation sources for particle-production with respect to the stopping (net-baryon) rapidity distributions. To represent the centrality dependence of charged-hadron production in asymmetric systems over a broad region of pseudorapidities, the consideration and precise modeling of the fragmentation sources, along with the central gluon-gluon source, is found to be essential. Specifically, this results in an inversion of the particle-production amplitude from backward to forward dominance when transitioning from central to peripheral collisions, in agreement with recent ATLAS and ALICE p-Pb data at sNN=5.02TeV.

Published by the American Physical Society
2024
Experience, knowledge, practices and attitudes of emergency department medical staff regarding teledermatology
Authors: Walter Sophie , Chiew Angela L , Martin Linda K 
Published: October 2024

AbstractObjectivesThe present study aimed to assess self‐reported experience, knowledge, practices and attitudes of ED medical staff regarding teledermatology.MethodsOnline questionnaire of ED medical staff at Prince of Wales Hospital (Sydney, Australia).ResultsSeventy‐nine staff completed the questionnaire. Photographic technique and compliance with medicolegal policies were variable: 1% obtained written consent and 45.6% documented verbal consent for photography. 54.4% of respondents had concerns about the quality of their photographs.ConclusionsSkin photography image quality, knowledge and adherence to medicolegal policy were poor among ED medical staff. Education could reduce risk and improve outcomes.