bluuebunny/crossref_metadata_2025 huggingface dataset:
A Versatile Functional Interaction between Electrically Silent KVSubunits and KV7 Potassium Channels
Authors: Renigunta Vijay , Xhaferri Nermina , Shaikh Imran Gousebasha , Schlegel Jonathan , Bisen Rajeshwari , Sanvido Ilaria , Kalpachidou Theodora , Kummer Kai , Oliver Dominik , Leitner Michael G. , Lindner Moritz
Published: February 2024

Voltage-gated K+(KV) channels govern K+-ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KVchannels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving raise to currents distinct from those of homomeric KV2 channels.

Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our finding demonstrate that KVcross-family interaction is much more versatile than previously thought – possibly serving nature to shape potassium conductance to the needs of individual cell types.
Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB Activity
Authors: Chen Hao , Hinz Kaitlyn , Zhang Chen , Rodriguez Yssa , Williams Sha Neisha , Niu Mengwei , Ma Xiaowen , Chao Xiaojuan , Frazier Alexandria L. , McCarson Kenneth E. , Wang Xiaowan , Peng Zheyun , Liu Wanqing , Ni Hong-Min , Zhang Jianhua , Swerdlow Russell H. , Ding Wen-Xing
Published: February 2024

Alcohol consumption is believed to affect Alzheimer’s disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is in turn regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression. To explore the effect of alcohol on brain TFEB and autophagy, we exposed young (3-month old) and aged (23-month old) mice to two alcohol-feeding paradigms and assessed biochemical, transcriptome, histology, and behavioral endpoints. In young mice, alcohol decreased hippocampal nuclear TFEB staining but increased SQSTM1/p62, LC3-II, ubiquitinated proteins, and phosphorylated Tau. Hippocampal TFEB activity was lower in aged mice than it was in young mice, and Gao-binge alcohol feeding did not worsen the age-related reduction in TFEB activity. To better assess the impact of chronic alcohol exposure, we fed young and aged mice alcohol for four weeks before completing Morris Water and Barnes Maze spatial memory testing. The aged mice showed worse spatial memory on both tests. While alcohol feeding slightly impaired spatial memory in the young mice, it had little effect or even slightly improved spatial memory in the aged mice. These findings suggest that aging is a far more important driver of spatial memory impairment and reduced autophagy flux than alcohol consumption.
A generic noninvasive neuromotor interface for human-computer interaction
Authors:   CTRL-labs at Reality Labs, Sussillo David , Kaifosh Patrick , Reardon Thomas
Published: February 2024

Since the advent of computing, humans have sought computer input technologies that are expressive, intuitive, and universal. While diverse modalities have been developed, including keyboards, mice, and touchscreens, they require interaction with an intermediary device that can be limiting, especially in mobile scenarios. Gesture-based systems utilize cameras or inertial sensors to avoid an intermediary device, but they tend to perform well only for unobscured or overt movements. Brain computer interfaces (BCIs) have been imagined for decades to solve the interface problem by allowing for input to computers via thought alone. However high-bandwidth communication has only been demonstrated using invasive BCIs with decoders designed for single individuals, and so cannot scale to the general public. In contrast, neuromotor signals found at the muscle offer access to subtle gestures and force information. Here we describe the development of a noninvasive neuromotor interface that allows for computer input using surface electromyography (sEMG). We developed a highly-sensitive and robust hardware platform that is easily donned/doffed to sense myoelectric activity at the wrist and transform intentional neuromotor commands into computer input. We paired this device with an infrastructure optimized to collect training data from thousands of consenting participants, which allowed us to develop generic sEMG neural network decoding models that work across many people without the need for per-person calibration. Test users not included in the training set demonstrate closed-loop median performance of gesture decoding at 0.5 target acquisitions per second in a continuous navigation task, 0.9 gesture detections per second in a discrete gesture task, and handwriting at 17.0 adjusted words per minute. We demonstrate that input bandwidth can be further improved up to 30% by personalizing sEMG decoding models to the individual, anticipating a future in which humans and machines co-adapt to provide seamless translation of human intent. To our knowledge this is the first high-bandwidth neuromotor interface that directly leverages biosignals with performant out-of-the-box generalization across people.
Genetic and physical interactions reveal overlapping and distinct contributions to meiotic double-strand break formation inC. elegans
Authors: Raices Marilina , Balmir Fabiola , Silva Nicola , Li Wei , Grundy McKenzie K. , Hoffman Dane K. , Altendorfer Elisabeth , Camacho Carlos Jaime , Bernstein Kara A. , Colaiácovo Monica P. , Yanowitz Judith
Published: February 2024

Double-strand breaks (DSBs) are the most deleterious lesions experienced by our genome. Yet, DSBs are intentionally induced during gamete formation to promote the exchange of genetic material between homologous chromosomes. While the conserved topoisomerase-like enzyme Spo11 catalyzes DSBs, additional regulatory proteins—referred to as “Spo11 accessory factors”— regulate the number, timing, and placement of DSBs during early meiotic prophase ensuring that SPO11 does not wreak havoc on the genome. Despite the importance of the accessory factors, they are poorly conserved at the sequence level suggesting that these factors may adopt unique functions in different species. In this work, we present a detailed analysis of the genetic and physical interactions between the DSB factors in the nematodeCaenorhabditis elegansproviding new insights into conserved and novel functions of these proteins. This work shows that HIM-5 is the determinant of X-chromosome-specific crossovers and that its retention in the nucleus is dependent on DSB-1, the sole accessory factor that interacts with SPO-11. We further provide evidence that HIM-5 coordinates the actions of the different accessory factors sub-groups, providing insights into how components on the DNA loops may interact with the chromosome axis.
Kir6.2-KATPchannels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis
Authors: Constantino Nicholas J. , Carroll Caitlin M. , Williams Holden C. , Yuede Carla M. , Sheehan Patrick W. , Andy Snipes J. , Musiek Erik S. , Johnson Lance A. , Macauley Shannon L.
Published: February 2024

Metabolism plays an important role in the maintenance of vigilance states (e.g. wake, NREM, and REM). Brain lactate fluctuations are a biomarker of sleep. Increased interstitial fluid (ISF) lactate levels are necessary for arousal and wake-associated behaviors, while decreased ISF lactate is required for sleep. ATP-sensitive potassium (KATP) channels couple glucose-lactate metabolism with neuronal excitability. Therefore, we explored how deletion of neuronal KATPchannel activity (Kir6.2-/- mice) affected the relationship between glycolytic flux, neuronal activity, and sleep/wake homeostasis. Kir6.2-/- mice shunt glucose towards glycolysis, reduce neurotransmitter synthesis, dampen cortical EEG activity, and decrease arousal. Kir6.2-/- mice spent more time awake at the onset of the light period due to altered ISF lactate dynamics. Together, we show that Kir6.2-KATPchannels act as metabolic sensors to gate arousal by maintaining the metabolic stability of each vigilance state and providing the metabolic flexibility to transition between states.

Highlights

Glycolytic flux is necessary for neurotransmitter synthesis. In its absence, neuronal activity is compromised causing changes in arousal and vigilance states despite sufficient energy availability.

With Kir6.2-KATPchannel deficiency, the ability to both maintain and shift between different vigilance states is compromised due to changes in glucose utilization.

Kir6.2-KATPchannels are metabolic sensors under circadian control that gate arousal and sleep/wake transitions.

Graphical Abstract
Identifying HRV and EEG correlates of well-being using ultra-short, portable, and low-cost measurements
Authors: Cannard Cédric , Delorme Arnaud , Wahbeh Helané
Published: February 2024

Wearable electroencephalography (EEG) and electrocardiography (ECG) devices may offer a non-invasive, user-friendly, and cost-effective approach for assessing well-being (WB) in real-world settings. However, challenges remain in dealing with signal artifacts (such as environmental noise and movements) and identifying robust biomarkers. We evaluated the feasibility of using portable hardware to identify potential EEG and heart-rate variability (HRV) correlates of WB. We collected simultaneous ultrashort (2-minute) EEG and ECG data from 60 individuals in real-world settings using a wrist ECG electrode connected to a 4-channel wearable EEG headset. These data were processed, assessed for signal quality, and analyzed using the open-source EEGLAB BrainBeats plugin to extract several theory-driven metrics as potential correlates of WB. Namely, the individual alpha frequency (IAF), frontal and posterior alpha asymmetry, and signal entropy for EEG. SDNN, the low/high frequency (LF/HF) ratio, the Poincaré SD1/SD2 ratio, and signal entropy for HRV. We assessed potential associations between these features and the main WB dimensions (hedonic, eudaimonic, global, physical, and social) implementing a pairwise correlation approach, robust Spearman’s correlations, and corrections for multiple comparisons. Only 8 files showed poor signal quality and were excluded from the analysis. Eudaimonic (psychological) WB was positively correlated with SDNN and the LF/HF ratio. EEG posterior alpha asymmetry was positively correlated with Physical WB (i.e., sleep and pain levels). No relationships were found with the other metrics, or between EEG and HRV metrics. These physiological metrics enable a quick, objective assessment of well-being in real-world settings using scalable, user-friendly tools.
Coordination between cytoskeletal organization, cell contraction and extracellular matrix development, is depended on LOX for aneurysm prevention
Authors: Aviram Rohtem , Zaffryar-Eilot Shelly , Kaganovsky Anna , Odeh Anas , Melamed Shay , Militsin Ruslana , Pinnock Cameron B. , Shemesh Ariel , Palty Raz , Ganesh Santhi K. , Hasson Peleg
Published: February 2024

Distinct, seemingly independent, cellular pathways affecting intracellular machineries or extracellular matrix (ECM) deposition and organization, have been implicated in aneurysm formation. One of the key genes associated with the pathology in both humans and mice is Lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deletedLoxin smooth muscle cells. We find that cytoskeletal organization is lost followingLoxdeletion. Cell culture assays and in vivo analyses demonstrate a cell-autonomous role for LOX affecting myosin light chain phosphorylation and cytoskeletal assembly resulting in irregular smooth muscle contraction. These results not only highlight new intracellular roles for LOX, but notably they link between multiple processes leading to aneurysm formation suggesting LOX coordinates ECM development, cytoskeletal organization and cell contraction required for media development and function.
Detection ofMansonella ozzardiin patients with acute febrile illness in Colombia
Authors: Ciuoderis Karl A. , Zamanian Mostafa , Perez Laura , Patiño Claudia , Maya Maria Angelica , Chan John D. , Cloherty Gavin A. , Hernandez-Ortiz Juan P. , Osorio Jorge E.
Published: February 2024

Mansonellosis is a vector-borne filariasis caused by parasitic nematodes of the genusMansonella. The prevalence and health impact of mansonellosis is largely unknown, and there are no control programmes targeting this neglected tropical disease. Mansonellosis is prevalent in certain regions of Colombia, and while infection is often thought to be asymptomatic it may be associated with underrecognized clinical manifestations. In this study, we analyzed biobanked specimens from 905 patients participating in a febrile syndrome surveillance program in Colombia for evidence ofMansonella ozzardiinfection, identifying four confirmed cases. While there have been prior reports on the incidence of mansonellosis in Colombia, this is the first report to our knowledge describingM. ozzardimicrofilariae occurring in febrile patients in the country. Additional studies are needed to better understand the clinical consequences of mansonellosis within the complex tropical environment of Colombia, which is endemic for numerous other blood-transmitted and other vector-borne pathogens.
The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy
Authors: Wang Wenjuan , Li Ermin , Zou Jianqiu , Qu Chen , Ayala Juan , Wen Yuan , Islam Md Sadikul , Weintraub Neal L. , Fulton David J. , Liang Qiangrong , Zhou Jiliang , Liu Jinbao , Li Jie , Sun Yi , Su Huabo
Published: February 2024

Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. While the role of ubiquitin (Ub) ligase PARKIN in mitophagy has been extensively studied, increasing evidence suggests the existence of PARKIN-independent mitophagy in highly metabolically active organs such as the heart. Here, we identify a crucial role for Cullin-RING Ub ligase 5 (CRL5) in basal mitochondrial turnover in cardiomyocytes. CRL5 is a multi-subunit Ub ligase comprised by the catalytic RING box protein RBX2 (also known as SAG), scaffold protein Cullin 5 (CUL5), and a substrate-recognizing receptor. Analysis of the mitochondrial outer membrane-interacting proteome uncovered a robust association of CRLs with mitochondria. Subcellular fractionation, immunostaining, and immunogold electron microscopy established that RBX2 and Cul5, two core components of CRL5, localizes to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, and increased cell death in cardiomyocytes.In vivo, deletion of theRbx2gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. Notably, the action of RBX2 in mitochondria is not dependent on PARKIN, and PARKIN gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 in mitochondria. Proteomics and biochemical analyses further revealed a global impact of RBX2 deficiency on the mitochondrial proteome and identified several mitochondrial proteins as its putative substrates. These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that controls mitophagy under physiological conditions in a PARKIN-independent, PINK1-dependent manner, thereby regulating cardiac homeostasis.
Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets
Authors: Vinel Claire , Boot James , Jin Weiwei , Pomella Nicola , Mein Charles , Zabet Nicolae Radu , Marino Silvia
Published: February 2024

Analysis of chromatin remodelling in neoplastic stem cells as compared to ontogenetically related neural stem cells, reveals multifactorial epigenetic regulation of signalling pathways known to contribute to glioblastoma development. It also identifies novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2 which could be further developed for future translational approaches to more effectively treat this neoplasm.
The Impact on Well-Being of Cognitive Bias about Infectious Diseases
Authors: Pestow Radomir
Published: February 2024

We investigate the relationship between bias about the severity of infectious disease and social well-being. First, we establish empirically the existence of bias and some of its causes; specifically, during the COVID-19 pandemic. Second, we derive an integrated economic-epidemiological differential equation model from an agent-based model that combines myopic rational choice with infectious disease dynamics. Third, we characterize axiomatically a model of an ethical, impartial, eudaemonistic and individualist observer. We proof that such an observer evaluates the state of society (social welfare or well-being) according to the utilitarian principle. Fourth, we show numerically, that while increased risk-perception indeed improves epidemio- logical outcomes such as peak of infections and total incidence, the impact on social well-being is ambiguous. This result urges to look beyond cases and deaths. Finally, we point out three possible future research directions and highlight some critical issues that arise in the normative direction.
Imaging brain vascular function in Cystic Fibrosis: an MRI study of cerebral blood flow and brain oxygenation
Authors: Chandler HL , Germuska M , Lancaster TM , Xanthe C , O’leary C , Stirk S , Murphy K , Metzler-Baddeley C , Wise RG , Duckers J
Published: February 2024

Cystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities have been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in patients with CF (PwCF). In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Compared to healthy controls, PwCF showed elevated CMRO2(p =0.015). There were no significant between-group differences in grey-matter CBF (p =0.342), or whole brain OEF (p =0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p< .05, FDR). This is the first study to characterise cerebrovascular function and brain oxygen metabolism in PwCF. Our findings highlight the need for early cardiovascular monitoring procedures to help maintain cerebrovascular function and combat accelerated aging effects in the brains of PwCF.
Quantification of metabolic activity from isotope tracing data using automated methodology
Authors: Liu Shiyu , Liu Xiaojing , Locasale Jason W.
Published: February 2024

Isotope tracing is a widely used technique to study metabolic activities by introducing heavy labeled nutrients into living cells and organisms. However, interpreting isotope tracing data is often heuristic, and application of automated methods using artificial intelligence is limited due to the paucity of evaluative knowledge. Our study developed a new pipeline that efficiently predicts metabolic activity in expansive metabolic networks and systematically quantifies flux uncertainty of traditional computational methods. We further developed an algorithm adept at significantly reducing this uncertainty, enabling robust evaluations of metabolic activity with limited data. Using this technology, we discovered highly reprogrammed mitochondria-cytosol exchange cycles in tumor tissue of patients, and observed similar metabolic patterns influenced by nutritional conditions in cancer cells. Thus, our refined methodology provides robust automated quantification of metabolism allowing for new insight into metabolic network activity.
Holimap: an accurate and efficient method for solving stochastic gene network dynamics
Authors: Jia Chen , Grima Ramon
Published: February 2024

Gene-gene interactions are crucial to the control of sub-cellular processes but our understanding of their stochastic dynamics is hindered by the lack of simulation methods that can accurately and efficiently predict how the distributions of gene product numbers for each gene vary across parameter space. To overcome these difficulties, here we present Holimap (high-order linear-mapping approximation), an approach that approximates the protein or mRNA number distributions of a complex gene regulatory network by the distributions of a much simpler reaction system. We demonstrate Holimap's computational advantages over conventional methods by applying it to predict the stochastic time-dependent dynamics of various gene networks, including transcriptional networks ranging from simple autoregulatory loops to complex randomly connected networks, post-transcriptional networks, and post-translational networks. Holimap is ideally suited to study how the intricate network of gene-gene interactions results in precise coordination and control of gene expression.
Distinct streams for supervised and unsupervised learning in the visual cortex
Authors: Zhong Lin , Baptista Scott , Gattoni Rachel , Arnold Jon , Flickinger Daniel , Stringer Carsen , Pachitariu Marius
Published: February 2024

Representation learning in neural networks may be implemented with supervised or unsupervised algorithms, distinguished by the availability of feedback. In sensory cortex, perceptual learning drives neural plasticity, but it is not known if this is due to supervised or unsupervised learning. Here we recorded populations of up to 90,000 neurons simultaneously from the primary visual cortex (V1) and higher visual areas (HVA), while mice learned multiple tasks as well as during unrewarded exposure to the same stimuli. Similar to previous studies, we found that neural changes in task mice were correlated with their behavioral learning. However, the neural changes were mostly replicated in mice with unrewarded exposure, suggesting that the changes were in fact due to unsupervised learning. The neural plasticity was concentrated in the medial HVAs and obeyed visual, rather than spatial, learning rules. In task mice only, we found a ramping reward prediction signal in anterior HVAs, potentially involved in supervised learning. Our neural results predict that unsupervised learning may accelerate subsequent task learning, a prediction which we validated with behavioral experiments.
Volitional control of movement interacts with proprioceptive feedback in motor cortex during brain-computer interface control in humans
Authors: Liu Monica F. , Gaunt Robert A. , Collinger Jennifer L. , Downey John E. , Batista Aaron P. , Boninger Michael L. , Weber Douglas J.
Published: February 2024

Vision and proprioception regulate motor output during reaching. To study the effects of sensory input on motor control, brain computer interfaces (BCIs) offer particular advantages. As part of a long-term clinical BCI trial, we implanted two 96-channel microelectrode arrays into M1 of a person who was completely paralyzed below the neck but retained intact somatosensation. Neural recordings from M1 were transformed into a 2-dimensional velocity control signal for a robotic arm using an optimal linear estimator decoder that was calibrated while the participant imagined performing movements demonstrated by a virtual arm. Once the decoder was calibrated, we asked the participant to move the robotic arm left and right past a pair of lines as many times as possible in one minute. We examined how visual and proprioceptive feedback were incorporated into BCI control during this task by providing the participant with either visual or proprioceptive feedback, both, or neither. Proprioceptive feedback was provided by moving the participant’s own arm to match the movement of the robotic arm. Task performance with vision or proprioception alone was better than when neither were provided. However, providing proprioceptive feedback impaired performance relative to visual feedback alone, unless the decoder was calibrated with neural data collected while both visual and proprioceptive feedback were provided. Providing proprioceptive feedback during decoder calibration rescued performance because it better captured M1’s neural activity during BCI control with proprioceptive feedback. In general, BCI performance was positively correlated with how well the decoder captured variance in neural activity during the task. In summary, we found that while the BCI participant was able to use proprioceptive feedback regardless of whether the decoder was trained with vision only or vision and proprioception, training the decoder with both visual and proprioceptive feedback made performance more robust to the addition or removal of visual or proprioceptive feedback. This was because training a decoder with proprioceptive feedback allows the decoder to take advantage of proprioception-driven activity in M1. Overall, we demonstrated that natural sensation can be effectively combined with BCI to improve performance in humans.
Post-peak mpox in England: epidemiology, reinfection, and vaccine effectiveness – data from 2023
Authors: Charles Hannah , Thorley Katie , Turner Charlie , Bennet Kirsty F. , Andrews Nick , Bertran Marta , Mandal Sema , Amirthalingam Gayatri , Ramsay Mary E. , Mohammed Hamish , Sinka Katy
Published: February 2024

England, like other countries that experienced a large outbreak of emergent mpox in 2022, continued to record cases during 2023 at a low but steady frequency. Comprehensive national surveillance shows that cases continue to occur primarily among gay, bisexual and other men who have sex with men mostly in London. Of 137 cases in 2023, around half were acquired overseas, half were vaccinated, and one case of reinfection was reported. Eleven people required hospital care. High vaccination uptake, during 2022, has provided good coverage of those at higher risk of mpox. Using the screening method, vaccine effectiveness of one dose was estimated at 84%. None of the vaccinated cases in 2023 were hospitalised.
Statistical pitfalls of multiple exposures in causal observational studies and tools to address them
Authors: McIntyre Kevin J , Wiener Joshua C , Davies Smith Emma
Published: February 2024

The Table 2 Fallacy is an interpretation error commonly encountered in medical literature. This fallacy occurs when coefficient estimates in multivariable regression models, apart from that of the primary exposure, are interpreted as total effects on the outcome. Causal diagrams can be used to identify sets of covariates that, when adjusted for, allow for unbiased estimation and correct interpretation of multiple total effects of interest. However, proper investigation of multiple total effects requires fitting several regression models and conducting multiple inferences. As the number of inferences increases, so does the rate of a false positive finding, a phenomenon known as multiplicity. While multiple comparison procedures are recognized as a critical consideration of randomized controlled trials, opinion remains divided on their use within observational studies. This commentary highlights how multiplicity may arise alongside the Table 2 Fallacy, and how causal diagrams can be used in conjunction with multiple comparison procedures to simultaneously avoid this fallacy, control the risk of spurious findings, and further align the best practices of experimental and observational studies.
Knowledge, Perception, and Preventive Practices of Livestock Workers and Household Animal Owners Regarding Anthrax in Nigeria
Authors: Cadmus E. , Adesokan H.K. , Awosanya E.J. , Iziomo P.M. , Akinseye V.O. , Besong M.A. , Jolaoso A.O. , Bida A. Nma , Akangbou J.P. , Nwanga E. , Orum G T. , Omileye A.O , Adeleye A.A. , Owoicho S. , Taiwo O.J. , Ansumana R. , Vakuru C. , Cadmus S.I.
Published: February 2024

Anthrax disease outbreak is a significant public health and socioeconomic problem, especially in low and middle-income countries (LMIC) like Nigeria. Inadequate knowledge and poor preventive practices against the disease among livestock workers and household animal owners remain important for disease transmission. Following the recent outbreaks in Nigeria, a cross-sectional study was carried out to assess the knowledge, perception and preventive practices of livestock workers and household animal owners regarding anthrax and the associated socioeconomic implications in Nigeria.

A pretested, semi-structured, interviewer-administered questionnaire was used to elicit relevant information from the respondents (n=1025) in seven of the 36 states in Nigeria. Data were analysed using SPSS version 29. Univariate analysis was done and Chi-square test statistics was test for association between the knowledge/perception and other variables.

Of the 1025 respondents, 58.6% and 79.9% demonstrated good knowledge and positive perception towards anthrax. However, there were important exposure practices, including a lack of preventive measures against anthrax infection (22.0%). Besides, only 27.7% of the respondents knew about the anthrax vaccination programme for livestock in the study area. With respect to the socioeconomic effects of the disease outbreak, 23.8% of the respondents indicated that the regulations imposed during an anthrax outbreak affect their livestock-related activities, while 40.6% were worried they might go out of business due to the anthrax outbreak. The respondents’ knowledge of anthrax was significantly associated with higher education (p=0.000), level of awareness (p=0.000) and perception of risk (p=0.000).

The study reveals a relatively high level of perception but an average knowledge level regarding anthrax with associated socioeconomic impacts among livestock workers and household animal owners in Nigeria. An important knowledge gap includes the poor knowledge of the routine annual vaccination of animals. Hence, mitigation strategies should include educational programmes targeting this gap.
A Randomized, Controlled Clinical Trial Demonstrates Improved Cognitive Function in Senior Dogs Supplemented with a Senolytic and NAD+ Precursor Combination
Authors: Simon Katherine E. , Russell Katharine , Mondino Alejandra , Yang Chin-Chieh , Case Beth C , Anderson Zachary , Whitley Christine , Griffith Emily , Gruen Margaret E. , Olby Natasha J.
Published: February 2024

Age-related decline in mobility and cognition are associated with cellular senescence and NAD+ depletion in dogs and people. A combination of a novel NAD+ precursor and senolytic, LY-D6/2 was examined in this randomized controlled trial. Seventy dogs were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the three-month primary endpoint, and 51 reached the six-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p=0.02) with the largest decrease in the full dose group. There were no significant differences between groups in changes in measured activity. However, the proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 significantly improves owner-assessed cognitive function and may have broader effects on frailty, activity and happiness as reported by owners.
The transcriptional response of cortical neurons to concussion reveals divergent fates after injury
Authors: Alkaslasi Mor R. , Lloyd Eliza Y. H. , Gable Austin S. , Silberberg Hanna , Yarur Hector E. , Tsai Valerie S. , Sohn Mira , Margolin Gennady , Tejeda Hugo A. , Le Pichon Claire E.
Published: February 2024

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. We show that neurons that activate ATF3 upregulate stress-related genes while repressing many genes, including commonly used markers for these cell types. Using an inducible reporter linked to ATF3, we genetically mark damaged cells to track them over time. Notably, we find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and retains the ability to fire action potentials. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive kinase MAP3K12, also known as dual leucine zipper kinase (DLK), is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our novel approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts.
Modeling cancer dependency with deep graph models
Authors: Fu Hengyi , Zhao Bojin , Wang Peng
Published: February 2024

A fundamental premise for precision oncology is a catalog of diverse actionable targets that could enable personalized treatment. Large scale Genome-wide lost-of-function screens such as cancer dependency map have systematically identified single gene vulnerabilities in numerous cell lines. However, it remains challenging to scale such analyses to many clinical samples and untangle molecular networks underlying observed vulnerabilities. We developed a deep learning framework, DepGPS, combing graph neural networks with transformers to model the network interactions underlying tumor vulnerabilities. Our model demonstrated an improved ability to predict context-specific vulnerabilities over existing models and showed a higher responsiveness in perturbation analysis. Furthermore, perturbation induced dependency changes by our model demonstrated utility to support context-aware identification of synthetic lethal genes. Overall, our model represents a valuable tool to extend tumor vulnerability analyses to broader range of subjects and could help to decipher molecular networks dictating context-specific tumor vulnerabilities.
CTFFIND5 provides improved insight into quality, tilt and thickness of TEM samples
Authors: Elferich Johannes , Kong Lingli , Zottig Ximena , Grigorieff Nikolaus
Published: February 2024

Images taken by transmission electron microscopes are usually affected by lens aberrations and image defocus, among other factors. These distortions can be modeled in reciprocal space using the contrast transfer function (CTF). Accurate estimation and correction of the CTF is essential for restoring the high-resolution signal in cryogenic electron microscopy (cryoEM). Previously, we described the implementation of algorithms for this task in thecisTEM software package (Grant et al., 2018). Here we show that taking sample characteristics, such as thickness and tilt, into account can improve CTF estimation. This is particularly important when imaging cellular samples, where measurement of sample thickness and geometry derived from accurate modeling of the Thon ring pattern helps judging the quality of the sample. This improved CTF estimation has been implemented in CTFFIND5, a new version of thecisTEM program CTFFIND. We evaluated the accuracy of these estimates using images of tilted aquaporin crystals and eukaryotic cells thinned by focused ion beam milling. We estimate that with micrographs of sufficient quality CTFFIND5 can measure sample tilt with an accuracy of 3° and sample thickness with an accuracy of 5 nm.
The 5-HT7receptor antagonist SB 269970 ameliorates maternal fluoxetine exposure-induced impairment of synaptic plasticity in the prefrontal cortex of the offspring female mice
Authors: Bobula Bartosz , Kusek Magdalena , Hess Grzegorz
Published: February 2024

Background

Although the use of a selective serotonin reuptake inhibitor fluoxetine in depression during pregnancy is considered safe, it might increase the risk of affective disorders and cognitive symptoms in progeny. In animal models, maternal exposure to fluoxetine throughout gestation and lactation negatively affects the behavior of the offspring. Little is known about the effects of maternal fluoxetine on synaptic transmission and plasticity in the offspring cerebral cortex.

Methods

During pregnancy and lactation C57BL/6J mouse dams received fluoxetine (7.5 mg/kg/day) with drinking water. Female offspring mice received intraperitoneal injections of the selective 5-HT7receptor antagonist SB 269970 (2.5 mg/kg) for 7 days. Whole-cell and field potential electrophysiological recordings were performed in the medial prefrontal cortex (mPFC)ex vivobrain slices.

Results

Perinatal exposure to fluoxetine resulted in decreased field potentials and impaired long-term potentiation (LTP) in layer II/III of the mPFC of female young adult offspring. Neither the intrinsic excitability nor spontaneous excitatory postsynaptic currents were altered in layer II/III mPFC pyramidal neurons. In mPFC slices obtained from fluoxetine-treated mice that were administered SB 269970 both field potentials and LTP magnitude were restored and did not differ from controls.

Conclusions

Treatment of fluoxetine-exposed mice with a selective 5-HT7receptor antagonist, SB269970, normalizes synaptic transmission and restores the potential for plasticity in the mPFC of mice exposedin uteroand postnatally to fluoxetine.
Whole genome assembly of the Little Millet (Panicum sumatrense) genome: A climate resilient crop species
Authors: Das Rasmita Rani , Kumar Ashish , Baghel Dushyant Singh , Mahato Ajay K , Dey Nrisingha , Mukherjee Pulok K , Pradhan Seema
Published: February 2024

Little millet (Panicum sumatrense) belongs to one of the largest genera,Panicumcomprising of 500 species that are distributed especially in tropical and sub-tropical Asia as well as Africa. This is a climate resilient crop that has the ability to adapt to adverse growing conditions, especially drought. Added to this is the better nutritional profile of little millet, which has higher iron and fibre contents as compared with rice. These characteristics make it an important crop species that would be pivotal for ensuring food security. Generating genomic resources for the species is significant and will have implications in crop improvement. Therefore, in the present study we report thede novowhole genome sequence ofP. sumatrense. Long read sequencing and Hi-C based scaffolding resulted in a total of 279 scaffolds with N50 of 7.8Mb. The genome was annotated to predict protein coding genes and orthologous groups were analysed after comparison with various plant genomes. This high-quality genome assembly can be a valuable resource as future reference for genomic studies in this crop and related crop species.
A new interesting and unidentified Schmidtea species in Romania (Platyhelminthes, Tricladida, Dugesiidae)
Authors: Babalean Anda Felicia
Published: February 2024

This paper presents the characters (morphology and aspects of reproductive biology) of a population belonging to the genusSchmidtea, in Romania. This population shows similarities with the other Schmidtea species: withS. polychroa, the presence of cephalic sensory fossae; withS. mediterranea, the asexual reproduction by fission; withS. nova, the presence of a diaphragm of the ejaculatory duct to the secondary seminal vesicle. Set of characters make the population distinct and thus, candidate for a new species: the disposition / arrangement of the genital atria; a wide and straight / narrow and convoluted ejaculatory duct within the penis papilla; in some specimens the penis papilla has two lobes, each with own duct.
Stress Granule-Related Genes during Embryogenesis of an Invertebrate Chordate
Authors: Drago Laura , Pennati Alessandro , Rothbächer Ute , Ashita Ryuji , Hashimoto Seika , Saito Ryota , Fujiwara Shigeki , Ballarin Loriano
Published: February 2024

Control of global protein synthesis through the assembly of stress granules (SGs) represents a strategy adopted by eukaryotic cells to face various stress conditions. TIAR, TTP and G3BP are key components of SGs, allowing the regulation of mRNA stability and thus controlling not only stress responses but also cell proliferation and differentiation. In the present work we aimed to investigate the role oftiar,ttpandg3bpduring embryogenesis of the solitary ascidianCiona robusta, both in physiological and stress conditions. We carried out CRISPR/Cas9 knockout to evaluate the effects on normal embryonic development, and gene reporter assays to study time and tissue specificity of gene expression, together with whole mount ISH and qRT-PCR. To induce acute stress conditions, we used iron and cadmium as “essential” and “non-essential” metals, respectively. Our results highlight, for the first time, the importance oftiar, ttpandg3bpin the control of development of mesendodermal tissue derivatives during embryogenesis of an invertebrate chordate.

HIGHLIGHTS

- Mesenchyme, nervous cells, and endoderm are the embryonic regions mainly transcribing

cr-tiarx1,cr-ttpandcr-g3bp2during metal stress conditions.

- Onlycr-ttptranscription is regulated at mid gastrula stage.

- The highest transcription levels are reached in hatching larvae after iron exposure.

-cr-tiarx1,cr-ttpandcr-g3bp2knockouts resulted in impaired embryogenesis.
“Long-Term Quarantine is Associated with High Cortisol and Low DNA Methylation in New World monkeys”
Authors: Seenayah Shayna , Sanchez Nofre , Paredes Ursula M
Published: February 2024

Quarantines prevent infectious disease spread during primate transport, fostering acclimatisation. Environmental stress can lead to altered physiology, health risks, and epigenetic changes in other primates. We analysed PeruvianSaguinus fuscicollisandSaimiri macrodon, immobilised for 10 months in quarantine during the COVID-19 crisis, and compared them to wild counterparts to determine effects of quarantine as a stressor in New World monkeys.

Methods

Both quarantine and wild samples were collected from two riverine islands near the city of Iquitos, situated in the Peruvian Amazon (Island Muyuy and Padre Island). Cortisol levels in hair were quantified using ELISA (n=37; quarantine n=16; wild=21), and global DNA methylation levels were assessed for epigenetic comparison in dried blood spots (n=45; Quarantine: n=23; Wild: n=22), also utilising ELISA. Two-way ANOVA was employed to explore the effect of quarantine on cortisol and DNA methylation, considering the effect of species, and sex differences on these measurements.

Results

Cortisol analysis revealed a significant association between quarantine and elevated cortisol secretion when testing both species together and independently, with a greater difference between quarantine and wild forSaguinus fuscicollis. Quarantine was associated with global DNA hypomethylation when testing both species together, however, independent ANOVAs show there was no effect of quarantine onSaguinus fuscicollis, and a marginal significant effect of quarantine onSaimiri macrodon.

Discussion

New World monkey species displayed hormonal and epigenetic dysregulation 10-months after starting quarantine period, suggesting long-term physiological and genomic stress as a response to captivity. Species specific differences in stress adaptability might mediate observed effects.
Individual corticosterone response to intermittent swim stress predicts a shift in economic demand for ethanol from pre- stress to post-stress in male rats
Authors: Robison Christopher L. , Madore Victoria , Cova Nicole , Drugan Robert C. , Charntikov Sergios
Published: February 2024

This study investigated the relationship between stress exposure and subsequent ethanol use, focusing on individual differences among male rats. We combined operant self-administration with behavioral economics to assess how intermittent swim stress affects ethanol consumption. This approach allowed for a nuanced analysis of the transition from regular ethanol intake to stress-induced escalation in economic demand. Results showed a consistent rise in ethanol demand post-stress among subjects, irrespective of exposure to actual swim stress or a sham procedure. This increase may result from a two-week abstinence or an inherent rise in demand over time. Significantly, we identified a direct link between post-stress corticosterone levels and the demand for ethanol, considering baseline levels. This correlation was particularly pronounced when examining the shifts in both corticosterone levels and demand for ethanol post-stress. However, neither post-stress corticosterone levels nor their change over time correlated significantly with changes in ethanol demand following a forced swim test that was administered 24 hours after the intermittent swim stress test. This suggests potential context-specific or stressor-specific effects. Importantly, pre-stress ethanol demand did not significantly predict the corticosterone response to stress, indicating that high ethanol-demand rats do not inherently exhibit heightened stress sensitivity. Our research brings to light the complex interplay between stress and ethanol consumption, highlighting the critical role of individual differences in this relationship. This research introduces a nuanced perspective, underscoring the need for future studies in the realm of stress and substance use to give greater consideration to individual variability.