bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep, NMDA Receptor Subunits, and the Compensatory Pathway: Understanding Contextual Fear Conditioning in the Absence of the Dorsal Hippocampus
Authors: Kant Deepika , Jha Sushil K. 
Published: June 2024

AbstractThe loss of the dorsal hippocampus (DH) results in profound deficits in contextual fear-conditioned (CxFC) memory. Nonetheless, CxFC memories can still form without the DH, specifically with multiple trials at three-day intervals. The infralimbic cortex (IL) is pivotal in initiating this compensatory process post-DH loss, but the precise factors remain elusive. Our study aims to delineate key factors of compensatory CxFC in DH absence by investigating the effects of sleep deprivation (SD) and NMDA receptor subunits NR2A and NR2B. Using a DH-lesioned rat model, we conducted two conditioning trials separated by three days and assessed fear response during the subsequent test. We observed that DH-lesioned animals exhibited to SD (DHL-SD) did not elicit a compensatory CxFC response, displaying significantly impaired freezing during the second test. Conversely, DH-lesioned non-sleep-deprived animals (DHL-NSD) compensated for DH loss and exhibited robust CxFC responses during the second test. Moreover, inhibiting NR2B subunits in the IL during initial CxFC training disrupted the formation of compensatory fear memory in DH-lesioned animals, while NR2A subunit blockade showed no significant effect. These emphasize the adverse impact of SD on compensatory memory and the critical role of NR2B subunits in facilitating compensatory CxFC memory formation following DH loss.
The impact of parvalbumin interneurons on visual discrimination depends on strength and timing of activation and task difficulty
Authors: Kukovska Lilia , Poort Jasper 
Published: June 2024

SUMMARYParvalbumin-expressing (PV) cells are the most common class of inhibitory interneurons in the visual cortex. They are densely connected to excitatory cells and play important roles in balancing cortical circuit activity and learning. PV cell activation is a tool to inactivate cortical regions to establish their role in visual processing. However, it is not established how moderate activation affects behaviour and how effects depend on activation strength, timing and task difficulty. We therefore investigated how these three major factors affect performance of mice in a go/no-go orientation discrimination task. We tested discrimination performance with different strength and timing of PV cell activation in V1 and with different task difficulty levels. We found that PV cell activation improved performance in easy discriminations when stimulating with moderate laser powers only during the initial 120 ms from stimulus onset, corresponding to the initial feedforward processing sweep across the cortical hierarchy. In the same animals, PV cell activation did not aid performance in difficult discriminations. However, in both easy and difficult discriminations, optimal behavioural performance required undisturbed late phase activity beyond 120 ms, highlighting the importance of sustained activity in V1. Combining the optogenetic activation of PV cells with two-photon imaging showed that behavioural changes were associated with changes in stimulus response selectivity in V1. Thus, our results demonstrate that early and sustained activity in V1 is crucial for perceptual discrimination and delineate specific conditions when PV cell activation shapes neuronal selectivity to improve behaviour.Effects of moderate optogenetic PV cell activation on behaviour are time window specificBenefits of increased PV cell-mediated inhibition depend on task difficultyOptimal behavioural performance requires sustained V1 activity in both easy and difficult discriminationsBehavioural changes with PV cell activation are reflected by changes in the selectivity of V1 neurons
pQEB1: a hospital outbreak plasmid lineage carryingblaKPC-2
Authors: Moran Robert A. , Behruznia Mahboobeh , Holden Elisabeth , Garvey Mark I. , McNally Alan 
Published: June 2024

AbstractWhile conducting genomic surveillance of carbapenemase-producing Enterobacteriaceae (CPEs) from patient colonisation and clinical infections at Birmingham’s Queen Elizabeth Hospital (QE), we identified an N-type plasmid lineage, pQEB1, carrying several antibiotic resistance genes including the carbapenemase geneblaKPC-2. The pQEB1 lineage is concerning due to its conferral of multi-drug resistance, its host range and apparent transmissibility, and its potential for acquiring further resistance genes. Representatives of pQEB1 were found in three sequence types (STs) ofCitrobacter freundii, two STs ofEnterobacter cloacae, and three species ofKlebsiella. Hosts of pQEB1 were isolated from 11 different patients who stayed in various wards throughout the hospital complex over a 13-month period from January 2023 to February 2024. At present, the only representatives of the pQEB1 lineage in GenBank were carried by anEnterobacter hormaecheiisolated from a blood sample at the QE in 2016 and aKlebsiella pneumoniaeisolated from a urine sample at University Hospitals Coventry and Warwickshire (UHCW) in May 2023. The UHCW patient had been treated at the QE.Long-read whole-genome sequencing was performed on Oxford Nanopore R10.4.1 flow cells, facilitating comparison of complete plasmid sequences. We identified structural variants of pQEB1 and defined the molecular events responsible for them. These have included IS26-mediated inversions and acquisitions of multiple insertion sequences and transposons, including carriers of mercury or arsenic resistance genes. We found that a particular inversion variant of pQEB1 was strongly associated with the QE Liver speciality after appearing in November 2023, but was found in different specialities and wards in January/February 2024. That variant has so far been seen in five different bacterial hosts from six patients, consistent with recent and ongoing inter-host and inter-patient transmission of pQEB1 in this hospital setting.
Investigating Statistical Power of Differential Abundance Studies
Authors: Agronah Michael , Bolker Benjamin M. 
Published: June 2024

AbstractIdentifying microbial taxa that differ in abundance between groups (control/treatment, healthy/diseased, etc.) is important for both basic and applied science. As in all scientific research, microbiome studies must have good statistical power to detect taxa with substantially different abundance between treatments; low power leads to poor precision and biased estimates via the “winner’s curse”. Several studies have raised concerns about low power in microbiome studies. In this study, we investigate statistical power in differential abundance analysis. In particular, we present a novel approach for estimating the statistical power to detect effects at the level of individual taxa as a function of effect size (fold change) and mean abundance. We analysed seven real case-control microbiome datasets and developed a novel method for simulating microbiome data. We illustrate how power varies with effect size and mean abundance; our results suggest that typical differential abundance studies are underpowered for detecting changes in individual taxon.
Exposure of negative-sense viral RNA in the cytoplasm initiates innate immunity to West Nile virus
Authors: Genoyer Emmanuelle , Wilson Jonathan , Ames Joshua M. , Stokes Caleb , Moreno Dante , Etzyon Noa , Oberst Andrew , Gale Michael 
Published: June 2024

ABSTRACTFor many RNA viruses, immunity is triggered when RIG-I-like receptors (RLRs) detect viral RNA. However, only a minority of infected cells undergo innate immune activation. By examining these “first responder” cells during West Nile virus infection, we found that specific accumulation of anti- genomic negative-sense viral RNA (-vRNA) underlies innate immune activation and that RIG-I preferentially interacts with -vRNA. However, flaviviruses sequester -vRNA into membrane-bound replication compartments away from cytosolic sensors. We found that single-stranded -vRNA accumulates outside of replication compartments in “first responder” cells, rendering it accessible to RLRs. Exposure of this -vRNA occurs at late timepoints of infection, is linked to viral assembly, and depends on the expression of viral structural proteins. These findings reveal that while most infected cells replicate high levels of vRNA, release of -vRNA from replication compartments during assembly occurs at low frequency and is critical for initiation of innate immunity during flavivirus infection.
Spiking networks that efficiently process dynamic sensory features explain receptor information mixing in somatosensory cortex
Authors: Koren Veronika , Emanuel Alan J. , Panzeri Stefano 
Published: June 2024

AbstractHow do biological neural systems efficiently encode, transform and propagate information between the sensory periphery and the sensory cortex about sensory features evolving at different time scales? Are these computations efficient in normative information processing terms? While previous work has suggested that biologically plausible models of of such neural information processing may be implemented efficiently within a single processing layer, how such computations extend across several processing layers is less clear. Here, we model propagation of multiple time-varying sensory features across a sensory pathway, by extending the theory of efficient coding with spikes to efficient encoding, transformation and transmission of sensory signals. These computations are optimally realized by a multilayer spiking network with feedforward networks of spiking neurons (receptor layer) and recurrent excitatory-inhibitory networks of generalized leaky integrate-and-fire neurons (recurrent layers). Our model efficiently realizes a broad class of feature transformations, including positive and negative interaction across features, through specific and biologically plausible structures of feedforward connectivity. We find that mixing of sensory features in the activity of single neurons is beneficial because it lowers the metabolic cost at the network level. We apply the model to the somatosensory pathway by constraining it with parameters measured empirically and include in its last node, analogous to the primary somatosensory cortex (S1), two types of inhibitory neurons: parvalbumin-positive neurons realizing lateral inhibition, and somatostatin-positive neurons realizing winner-take-all inhibition. By implementing a negative interaction across stimulus features, this model captures several intriguing empirical observations from the somatosensory system of the mouse, including a decrease of sustained responses from subcortical networks to S1, a non-linear effect of the knock-out of receptor neuron types on the activity in S1, and amplification of weak signals from sensory neurons across the pathway.
Arid1bhaploinsufficiency in cortical inhibitory interneurons causes cell-type-dependent changes in cellular and synaptic development
Authors: Marshall Alec H. , Boyle Danielle J. , Hanson Meretta A. , Nagarajan Devipriyanka , Bibi Noor , Safa Alireza , Johantges Aidan C. , Wester Jason C. 
Published: June 2024

ABSTRACTAutism spectrum disorder (ASD) presents with diverse cognitive and behavioral abnormalities beginning during early development. Although the neural circuit mechanisms remain unclear, recent work suggests pathology in cortical inhibitory interneurons (INs) plays a crucial role. However, we lack fundamental information regarding changes in the physiology of synapses to and from INs in ASD. Here, we used transgenic mice to conditionally knockout one copy of the high confidence ASD risk geneArid1bfrom the progenitors of parvalbumin-expressing fast-spiking (PV-FS) INs and somatostatin-expressing non-fast-spiking (SST-NFS) INs. In brain slices, we performed paired whole-cell recordings between INs and excitatory projection neurons (PNs) to investigate changes in synaptic physiology. In neonates, we found reduced synaptic input to INs but not PNs, with a concomitant reduction in the frequency of spontaneous network events, which are driven by INs in immature circuits. In mature mice, we found a reduction in the number of PV-FS INs in cortical layers 2/3 and 5. However, changes in PV-FS IN synaptic physiology were cortical layer and PN cell-type dependent. In layer 5, synapses from PV-FS INs to subcortical-projecting PNs were weakened. In contrast, in layer 2/3, synapses to and from PV-FS INs and corticocortical-projecting PNs were strengthened, leading to enhanced feedforward inhibition of input from layer 4. Finally, we found a novel synaptic deficit among SST-NFS INs, in which excitatory synapses from layer 2/3 PNs failed to facilitate. Our data highlight that changes in unitary synaptic dynamics among INs in ASD depend on neuronal cell-type.
Integrated multi-platform approaches to gain insights into ecosystem’s fundamental ecology and habitat specific alterations
Authors: Nagar Shekhar , Talwar Chandni , Negi Ram Krishan 
Published: June 2024

AbstractThe increasing availability of metagenome-assembled genomes and environmental metagenomes provides unprecedented access to the metabolic potential and functional differences within the habitats. The hot spring microbiome with its diverse habitats and relatively well-characterized microbial inhabitants offers an opportunity to investigate core and habitat specific community structures at an ecosystem scale. Here, we employed tailored genome-resolved metagenomics and a novel approach that offers metagenomic overlaps to investigate the core and habitat-specific microbial diversity and multifunctionality of microbial residents of three habitats: microbial mat, sediment and water. We recovered 6% of the Ecosystem core community (ECC) in the habitats suggesting the widespread acquisition of Proteobacteria involving in the diverging trajectories of the hot spring and 72% of the Habitat specific community (HSC) in microbial mat, sediment and water habitats offers insights into specific adaptations due to extreme conditions. Strain-level resolution of metagenome-assembled genomes defined the habitat specific genotypes (HSGs) and comparative metagenomic analysis exposed ecosystem-core genotypes (ECGs). Further, the functional attributes of ECGs revealed a complete metabolic potential of nitrate reduction, ammonia assimilation and sulfate reduction. The highest cycling entropy scores (H’) of N cycle suggested the enrichment of nitrogen fixing microbes commonly present in all three habitats. While specifically HSGs possessed the amino acid transport and metabolism functions in microbial mat (9.5%) and water (13%) and 19% of translation, ribosomal structure and biogenesis in sediment. Our findings provide insights into population structure and multifunctionality in the different habitats of hot spring and form specific hypotheses about habitat adaptation. The results illustrated the supremacy of using genome-resolved metagenomics and ecosystem core metagenomics postulating the differential ecological functions rather than that of explaining the presence of functions within ecosystem.
Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome
Authors: Childers Laura , Park Jieun , Wang Siyao , Liu Richard , Barry Robert , Watts Stephen A. , Rawls John F. , Bagnat Michel 
Published: June 2024

AbstractDietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.
Acetaminophen Overdose Reveals Protease-Activated Receptor 4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium
Authors: Rajala Rahul , Cleuren Audrey C.A. , Griffin Courtney T. 
Published: June 2024

ABSTRACTBackground & AimsHepatic endothelial cell (EC) dysfunction and centrilobular hepatocyte necrosis occur with acetaminophen (APAP) overdose. The protease thrombin, which is acutely generated during APAP overdose, can signal through protease-activated receptors 1 and 4 (PAR1/PAR4). PAR1 is a high-affinity thrombin receptor that is known to signal on ECs, whereas PAR4 is a low-affinity thrombin receptor, and evidence for its expression and function on ECs is mixed. This study aims to exploit the high levels of thrombin generated during APAP overdose to determine (1) if hepatic endothelial PAR4 is a functional receptor, and (2) endothelial-specific functions for PAR1 and PAR4 in a high thrombin setting.MethodsWe generated mice with conditional deletion(s) ofPar1/Par4in ECs and overdosed them with APAP. Hepatic vascular permeability, erythrocyte congestion/bleeding, and liver function were assessed following overdose. Additionally, we investigated the expression levels of endothelial PARs and how they influence transcription in APAP-overdosed liver ECs using endothelial Translating Ribosome Affinity Purification followed by next-generation sequencing (TRAPseq).ResultsWe found that mice deficient in high-expressing endothelialPar1or low-expressingPar4had equivalent reductions in APAP-induced hepatic vascular instability but no effect on hepatocyte necrosis. Additionally, mice with loss of endothelialPar1andPar4had reduced permeability at an earlier time point after APAP overdose when compared to mice singly deficient in either receptor in ECs. We also found that endothelial PAR1—but not PAR4—can regulate transcription in hepatic ECs.ConclusionsLow-expressing PAR4 can react similarly to high-expressing PAR1 in APAP-overdosed hepatic ECs, demonstrating that PAR4 is a potent thrombin receptor. Additionally, these receptors are functionally redundant but act divergently in their expression and ability to influence transcription in hepatic ECs.NOMENCLATUREF2randF2rl3are the gene names for PAR1 and PAR4, respectively. For simplicity, we hereafter refer to these genes asPar1andPar4.
Lysosome damage triggers acute formation of ER to lysosomes membrane tethers mediated by the bridge-like lipid transport protein VPS13C
Authors: Wang Xinbo , Xu Peng , Bentley-DeSousa Amanda , Hancock-Cerutti William , Cai Shujun , Johnson Benjamin T , Tonelli Francesca , Shao Lin , Talaia Gabriel , Alessi Dario R. , Ferguson Shawn M. , De Camilli Pietro 
Published: June 2024

ABSTRACTBased on genetic studies, lysosome dysfunction is thought to play a pathogenetic role in Parkinson’s disease (PD). Here we show that VPS13C, a bridge-like lipid transport protein and a PD gene, is a sensor of lysosome stress/damage. Upon lysosome membrane perturbation, VPS13C rapidly relocates from the cytosol to the surface of lysosomes where it tethers their membranes to the ER. This recruitment depends on Rab7 and requires a signal at the damaged lysosome surface that releases an inhibited state of VPS13C which hinders access of its VAB domain to lysosome-bound Rab7. While another PD protein, LRRK2, is also recruited to stressed/damaged lysosomes, its recruitment occurs at much later stages and by different mechanisms. Given the role of VPS13 proteins in bulk lipid transport, these findings suggest that lipid delivery to lysosomes by VPS13C is part of an early protective response to lysosome damage.
Reconnecting sustainability reporting with earnings management: empirical evidence from Kuwait
Authors: Masmoudi Sana , Ben Salem Mamoun 
Published: June 2024

Purpose
This study aims to examine the impact of environmental, social and governance (ESG) reporting on accruals-based earnings management (AEM) activities in Kuwait.

Design/methodology/approach
Based on a random-effects regression analysis, this study examines the relationship between sustainability reporting (SR), as determined by the intensity degree method and EM, as measured by AEM, using panel data from 37 listed Kuwaiti companies on the Kuwait Stock Exchange between 2017 and 2021.

Findings
Empirical results reveal that SR affects EM in Kuwait. It appears that socially responsible Kuwaiti firms concentrate their efforts on fostering transparency and integrity in their interactions with stakeholders rather than engaging in misleading practices.

Practical implications
This study suggests a range of practical implications in Kuwait and similar economies. The findings highlight that SR can be advantageous for individuals, policymakers and corporations by promoting positive impact, addressing sustainability targets, building stakeholder confidence, reducing the risk of exposure to environmental, social and ethical liabilities and enhancing public well-being.

Originality/value
This study creates a unique ESG data set for Kuwait, unavailable in academic research. Building upon previous study that focused only on the environmental aspect (Gerged et al., 2020), this research, however, adopts a broader approach by investigating the overall impact of ESG reporting on EM in Kuwait, making it the first study to explore this relationship in this country.