bluuebunny/crossref_metadata_2025_split huggingface dataset:
R-loops acted on by RNase H1 are a determinant of chromosome length-associated DNA replication timing and genome stability inLeishmania
Authors: Damasceno Jeziel D. , Briggs Emma M. , Krasilnikova Marija , Marques Catarina A. , Lapsley Craig , McCulloch Richard 
Published: May 2024

AbstractGenomes in eukaryotes normally undergo DNA replication in a choreographed temporal order, resulting in early and late replicating chromosome compartments.Leishmania, a human protozoan parasite, displays an unconventional DNA replication program in which the timing of DNA replication completion is chromosome size-dependent: larger chromosomes complete replication later then smaller ones. Here we show that both R-loops and RNase H1, a ribonuclease that resolves RNA-DNA hybrids, accumulate inLeishmania majorchromosomes in a pattern that reflects their replication timing. Furthermore, we demonstrate that such differential organisation of R-loops, RNase H1 and DNA replication timing across the parasite’s chromosomes correlates with size-dependent differences in chromatin accessibility, G quadruplex distribution and sequence content. Using conditional gene excision, we show that loss of RNase H1 leads to transient growth perturbation and permanently abrogates the differences in DNA replication timing across chromosomes, as well as altering levels of aneuploidy and increasing chromosome instability in a size-dependent manner. This work provides a link between R-loop homeostasis and DNA replication timing in a eukaryotic parasite and demonstrates that orchestration of DNA replication dictates levels of genome plasticity inLeishmania.
Microstimulation reveals anesthetic state-dependent effective connectivity of neurons in cerebral cortex
Authors: Hudetz Anthony G 
Published: May 2024

AbstractComplex neuronal interactions underlie cortical information processing that can be compromised in altered states of consciousness. Here intracortical microstimulation was applied to investigate the state-dependent effective connectivity of neurons in rat visual cortex in vivo. Extracellular activity was recorded at 32 sites in layers 5/6 while stimulating with charge-balanced discrete pulses at each electrode in random order. The same stimulation pattern was applied at three levels of anesthesia with desflurane and in wakefulness. Spikes were sorted and classified by their waveform features as putative excitatory and inhibitory neurons. Microstimulation caused early (<10ms) increase followed by prolonged (11-100ms) decrease in spiking of all neurons throughout the electrode array. The early response of excitatory but not inhibitory neurons decayed rapidly with distance from the stimulation site over 1mm. Effective connectivity of neurons with significant stimulus response was dense in wakefulness and sparse under anesthesia. Network motifs were identified in graphs of effective connectivity constructed from monosynaptic cross-correlograms. The number of motifs, especially those of higher order, increased rapidly as the anesthesia was withdrawn indicating a substantial increase in network connectivity as the animals woke up. The results illuminate the impact of anesthesia on functional integrity of local circuits affecting the state of consciousness.
The Noisy Encoding of Disparity Model Predicts Perception of the McGurk Effect in Native Japanese Speakers
Authors: Magnotti John F. , Lado Anastasia , Beauchamp Michael S. 
Published: May 2024

AbstractThe McGurk effect is an illusion that demonstrates the influence of information from the face of the talker on the perception of auditory speech. The diversity of human languages has prompted many intercultural studies of the effect, including in native Japanese speakers. Studies of large samples of native English speakers have shown that the McGurk effect is characterized by high variability, both in the susceptibility of different individuals to the illusion and in the frequency with which different experimental stimuli induce the illusion. The noisy encoding of disparity (NED) model of the McGurk effect uses Bayesian principles to account for this variability by separately estimating the susceptibility and sensory noise for each individual and the strength of each stimulus. To test whether the NED model could account for McGurk perception in a non-Western culture, we applied it to data collected from 80 native Japanese-speaking participants. Fifteen different McGurk stimuli were presented, along with audiovisual congruent stimuli. The McGurk effect was highly variable across stimuli and participants, with the percentage of illusory fusion responses ranging from 3% to 78% across stimuli and from 0% to 91% across participants. Despite this variability, the NED model accurately predicted perception, predicting fusion rates for individual stimuli with 2.1% error and for individual participants with 2.4% error. Stimuli containing the unvoiced pa/ka pairing evoked more fusion responses than the voiced ba/ga pairing. Model estimates of sensory noise was correlated with participant age, with greater sensory noise in older participants. The NED model of the McGurk effect offers a principled way to account for individual and stimulus differences when examining the McGurk effect within and across cultures.
Analysis of Hippocampal Synaptic Function in a Rodent Model of Early Life Stress
Authors: Wilkinson Matthew P , Robinson Emma S J , Mellor Jack R 
Published: May 2024

AbstractBackgroundEarly life stress (ELS) is an important risk factor in the aetiology of depression. Developmental glucocorticoid exposure impacts multiple brain regions with the hippocampus being particularly vulnerable. Hippocampal mediated behaviours are dependent upon the ability of neurones to undergo long-term potentiation (LTP), an N-methyl-D-aspartate receptor (NMDAR) mediated process. In this study we investigated the effect of ELS upon hippocampal NMDAR function.MethodsHooded Long-Evans rat pups (n=82) were either undisturbed or maternally separated for 180 minutes per day (MS180) between post-natal day (PND) 1 and PND14. Model validation consisted of sucrose preference (n=18) and novelty supressed feeding (NSFT, n=34) tests alongside assessment of corticosterone (CORT) and paraventricular nucleus (PVN) cFos reactivity to stress and hippocampal neurogenesis (all n=18). AMPA/NMDA ratios (n=19), miniEPSC currents (n=19) and LTP (n=15) were assessed in whole-cell patch clamp experiments in CA1 pyramidal neurones.ResultsMS180 animals showed increased feeding latency in the NSFT alongside increased overall CORT in the restraint stress experiment and increased PVN cFos expression in males but no changes in neurogenesis or sucrose preference. MS180 was associated with a lower AMPA/NMDA ratio with no change in miniEPSC amplitude or area. There was no difference in short- or long-term potentiation between MS180 and control animals nor were there any changes during the induction protocol.ConclusionsThe MS180 model showed a behavioural phenotype consistent with previous work. MS180 animals showed increased NMDAR function with preliminary evidence suggesting that this was not concurrent with an increase in LTP.
A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology
Authors: Sutton Nate , Gutiérrez-Guzmán Blanca , Dannenberg Holger , Ascoli Giorgio A. 
Published: May 2024

AbstractComputational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties fromHippocampome.orgto study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal was to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies. We investigate the spiking dynamics in specific neuron types and the synaptic activities between groups of neurons. Modeling the rodent hippocampal formation keeps the simulations to a computationally reasonable scale while also anchoring the parameters and results to experimental measurements. Our model generates grid cell activity that well matches the spacing, size, and firing rates of grid fields recorded in live behaving animals from both published datasets and new experiments performed for this study. Our simulations also recreate different scales of those properties, e.g., small and large, as found along the dorsoventral axis of the medial entorhinal cortex. Computational exploration of neuronal and synaptic model parameters reveals that a broad range of neural properties produce grid fields in the simulation. These results demonstrate that the continuous attractor network model of grid cells is compatible with a spiking neural network implementation sourcing data-driven biophysical and anatomical parameters fromHippocampome.org. The software is released as open source to enable broad community reuse and encourage novel applications.
Alterations of PINK1-PRKN signaling in mice during normal aging
Authors: Baninameh Zahra , Watzlawik Jens O. , Hou Xu , Richardson Tyrique , Kurchaba Nicholas W. , Yan Tingxiang , Di Florio Damian N. , Fairweather DeLisa , Kang Lu , Nguyen Justin H. , Kanekiyo Takahisa , Dickson Dennis W. , Noda Sachiko , Sato Shigeto , Hattori Nobutaka , Goldberg Matthew S. , Ganley Ian G. , Stauch Kelly L. , Fiesel Fabienne C. , Springer Wolfdieter 
Published: May 2024

ABSTRACTThe ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studiedin vitroupon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagyin vivois less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessmentin vivo,setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.
Avian Influenza Virus Infections in Felines: A Systematic Review of Two Decades of Literature
Authors: Coleman Kristen K. , Bemis Ian G. 
Published: May 2024

AbstractAs an avian influenza virus (AIV) panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern. Domestic cats are susceptible to AIV infection and provide a potential pathway for zoonotic spillover to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of AIV infections in felines reported from 2004 – 2024. We identified 607 AIV infections in felines, including 302 associated deaths, comprising 18 countries and 12 felid species. We observed a drastic flux in the number of AIV infections among domestic cats in 2023 and 2024, commensurate with the emergence of H5N1 clade 2.3.4.4b. We estimate that this phenomenon is underreported in the scientific literature and argue that increased surveillance among domestic cats is urgently needed.
Reporting of paediatric exercise-induced respiratory symptoms by physicians and parents
Authors: Pedersen Eva SL , Glick Sarah , de Jong Carmen CM , Ardura-Garcia Cristina , Jochmann Anja , Casaulta Carmen , Hartog Katharina , Marangu-Boore Diana , Mueller-Suter Dominik , Regamey Nicolas , Singer Florian , Moeller Alexander , Kuehni Claudia E 
Published: May 2024

AbstractAims of the studyRoutinely collected health data are increasingly used for research, however important history items may be incomplete in medical records. We assessed clinical documentation of exercise-induced respiratory symptoms (EIS) by treating physicians and compared with parent-reported EIS for the same children.MethodsWe analysed data from the Swiss Paediatric Airway Cohort (SPAC), a multicentre observational study of children treated in Swiss outpatient pulmonology clinics. We included children 6 to 17 years of age who were referred to a paediatric pulmonologist for evaluation of EIS. Features of EIS recorded by physicians were extracted from outpatient clinical letters transmitted to the referring physician, while parent-reported EIS data were collected from a standardized questionnaire completed at SPAC enrolment. We calculated agreement between physician-documented and parent-reported EIS characteristics using Cohen’s and Fleiss’s kappa.ResultsOf 1669 children participating in SPAC (2017-2019), 193 (12%) met the inclusion criteria, of whom 48% were girls. Physicians provided detailed information on EIS in 186 (96%) outpatient clinical letters. Documented characteristics included: type of physical activity triggering EIS (69%), localisation of EIS in chest or throat (48%), respiratory phase of EIS (45%), and timing of EIS during or after exercise (37%). Previous bronchodilator use (94%) and its effect on EIS (88%) were consistently documented by physicians. The clinical letters of children diagnosed with dysfunctional breathing more often contained detailed EIS characteristics than for children diagnosed with asthma. The agreement between physician-documented and parent-reported EIS was moderate for use of bronchodilators (k=0.53) and poor to fair for all other features (k=0.01-0.36).ConclusionThis study highlights that outpatient clinical letters may lack some details on EIS characteristics, information which parents could provide. A standardized and detailed method for documenting paediatric respiratory symptoms in the coordinated data infrastructure may enhance future analyses of routinely collected health data.
Harmonizing multisite neonatal diffusion-weighted brain MRI data for developmental neuroscience
Authors: Bonthrone Alexandra F. , Blesa Cábez Manuel , Edwards A. David , Hajnal Jo V. , Counsell Serena J. , Boardman James P. 
Published: May 2024

AbstractLarge diffusion-weighted brain MRI (dMRI) studies in neonates are crucial for developmental neuroscience. Our aim was to investigate the utility of ComBat, and empirical Bayes tool for multisite harmonization, for removing site effects from white matter (WM) dMRI measures in healthy infants born 37-42+6 weeks from the Theirworld Edinburgh Birth Cohort (n=86) and Developing Human Connectome Project (n=287).Skeletonized fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD, RD) maps were harmonized. The differences between voxel-wise metrics, skeleton means and histogram widths (5th-95th percentile) were assessed before and after harmonization, as well as variance associated with gestational age at birth.Before harmonization, large cohort differences were observed in all measures. Harmonization removed all voxel-wise differences from MD maps and all metric means and histogram widths, however small voxel-wise differences (<1.5% of voxels) remained in FA, AD and RD. We detected significant relationships between GA at birth and all metrics. When comparing single site and multi-site harmonized datasets of equal sample sizes, harmonized data resulted in smaller standardized regression coefficients.ComBat will enable unprecedented sample sizes in developmental neuroscience, offering new horizons for biomarker discovery and validation, understanding typical and atypical brain development, and assessment of neuroprotective therapies.
The relationship between the size and asymmetry of the lateral ventricles and cortical myelin content in individuals with mood disorders
Authors: Manelis A , Hu H , Miceli R , Satz S , Lau R , Iyengar S , Swartz HA 
Published: May 2024

AbstractBackgroundAlthough enlargement of the lateral ventricles was previously observed in individuals with mood disorders, the link between ventricular size and asymmetry with other indices of brain structure remains underexplored. In this study, we examined the association of lateral ventricular size and asymmetry with cortical myelin content in individuals with bipolar (BD) and depressive (DD) disorders compared to healthy controls (HC).MethodsMagnetic resonance imaging (MRI) was used to obtain T1w and T2w images from 149 individuals (age=27.7 (SD=6.1) years, 78% female, BD=38, DD=57, HC=54). Cortical myelin content was calculated using the T1w/T2w ratio. Elastic net regularized regression identified brain regions whose myelin content was associated with ventricular size and asymmetry. A post-hoc linear regression examined how participants’ diagnosis, illness duration, and current level of depression moderated the relationship between the size and asymmetry of the lateral ventricles and levels of cortical myelin in the selected brain regions.ResultsIndividuals with mood disorders had larger lateral ventricles than HC. Larger ventricles and lower asymmetry were observed in individuals with BD who had longer lifetime illness duration and more severe current depressive symptoms. A greater left asymmetry was observed in participants with DD than in those with BD (p<0.01). Elastic net revealed that both ventricular enlargement and asymmetry were associated with altered myelin content in cingulate, frontal, and sensorimotor cortices. In BD, but not other groups, ventricular enlargement was related to altered myelin content in the right insular regions.ConclusionsLateral ventricular enlargement and asymmetry are linked to myelin content imbalance, thus, potentially leading to emotional and cognitive dysfunction in mood disorders.
Pharmacologic and genetic evidence converge on mechanisms of psychotic illness
Authors: Fennessy Brian , Cotter Liam , Simons Nicole W. , Liharska Lora E. , Nadkarni Girish N. , Ruderfer Douglas M. , Charney Alexander W. 
Published: May 2024

AbstractIdiopathic and substance-induced forms of psychotic illness afflict millions of people worldwide, and it is largely unknown whether these two forms emerge through the same molecular mechanisms. Though genetic studies have implicated thousands of genes in idiopathic psychotic illnesses (e.g., schizophrenia), consensus is lacking regarding which of these genes are most likely to treat psychotic illness when modulated pharmacologically and, as a result, antipsychotic medications targeting these genes have yet to be developed. Previous studies suggest that one way to determine if a candidate target gene is likely to lead to an effective treatment for a given illness is if the gene is implicated by multiple lines of evidence (e.g., genetic, pharmacologic). Here, pharmacologic, genetic, and clinical data were leveraged to determine if the idiopathic and substance-induced forms of psychotic illness are related to one another through a common set of genes. A set of medications that cause psychotic illness as a side effect (“propsychotics”) were identified by analyzing 15 million medication side effects reports from over 100 countries. There was a significant overlap of target genes among propsychotics and antipsychotics and for many of the shared target genes propsychotics act through a mechanism that was qualitatively the opposite of the mechanism through which antipsychotics act (e.g., activation vs. inhibition). Propsychotic and antipsychotic target genes were significantly enriched for genes implicated in schizophrenia by rare loss-of-function genetic variation but not for genes implicated in schizophrenia by common genetic variation. Only one gene –GRIN2A, encoding the GluN2A subunit of the NMDA glutamate receptor – was implicated in psychotic illness by propsychotics, rare loss-of-function genetic variation, and common genetic variation. Mining genetic data from a diverse cohort of 30,000 adults treated in a New York City health system, a carrier of a rare loss-of-function variant inGRIN2Awith severe psychotic illness was identified with a clinical course notable for psychotic symptoms and cognitive deficits that are not targeted by current antipsychotics. Altogether, this report shows how integrating pharmacologic, genetic, and clinical data from large cohorts can prioritize target genes for novel drug development and align the prioritized targets with specific clinical presentations.
A multi-centre cross-sectional study on hepatitis B vaccination coverage and associated factors among personnel working in health facilities in Kumasi, Ghana
Authors: Okwan Daniel Kobina , Scott Godfred Yawson , Takyi Pius , Boateng Clinton Owusu , Antwi Philemon Boasiako , Abrampah Akwasi Amponsah , Obeng Michael Agyemang 
Published: May 2024

AbstractAs part of efforts to reach the elimination target by 2030, the WHO and CDC recommend that all HCWs adhere to the 3-dose hepatitis B vaccination schedule to protect themselves against the infection. This study assessed Hepatitis B vaccination coverage and associated factors among personnel working in health facilities in Kumasi, Ghana.A cross-sectional study involving 530 HCWs was conducted in four hospitals in Kumasi from September to November, 2023. An investigator-administered questionnaire was employed in gathering participant demographics and other information related to vaccination coverage. IBM SPSS version 26.0 and GraphPad prism 8.0 were used for analysing the data.Even though, majority (70.6%) reported having taken at least one dose of the vaccine, only 43.6% were fully vaccinated (≥ 3 doses). More than a quarter (29.4%) had not taken any dose of the HBV vaccine. Close to a quarter (23.6%) had not screened or tested for HBV infection in their lifetime. The Statistically significant variables influencing vaccination status were age, marital status, profession and status in the hospital. Majority (44.9%) of the participants who have not taken the vaccine reported they do not have reason for not taking the vaccine and high proportion (80.1%) were willing to take the vaccine when given for free.To combat the low hepatitis B vaccination coverage among healthcare workers in Kumasi, Ghana, amidst the significant public health threat of HBV infection, comprehensive measures are necessary. These include implementing infection prevention control programmes, enhancing occupational health and safety, and conducting health promotion campaigns in healthcare facilities. Extending and intensifying hepatitis B screening and vaccination initiatives to tertiary institutions and encouraging employers, supervisors or team leaders to provide these services nationwide are also recommended.