bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental and Historical Determinants of African Horse Sickness: Insights from Predictive Modeling
Authors: Kim KwangHyok , Xu TianGang , Villalan Arivizhivendhan Kannan , Chi TianYing , Yu XiaoJing , Jin MyongIl , Wu RenNa , Ni GuanYing , Sui ShiFeng , Wang ZhiLiang , Wang XiaoLong 
Published: February 2024

AbstractThis study marks a pioneering effort in analyzing the global epidemiological patterns of African Horse Sickness (AHS) across different regions. By employing predictive modeling with a comprehensive set of environmental variables, we uncovered overarching global patterns in AHS dynamics, a first in this field. Our analysis revealed significant regional differences influenced by specific climatic conditions, highlighting the disease’s complexity. The study also identifies new high-risk areas for AHS, underscoring the necessity for regionally tailored disease management strategies. Despite some limitations, such as the exclusion of wild equine data, this research offers critical insights for global AHS intervention and prevention, setting a path for future research incorporating broader datasets and socio-economic factors.Author SummaryAHS presents a significant challenge to the global equine industry, impacting both health and economic aspects. Our study highlights the profound effect of climate change, particularly the frequency of extreme climatic events including temperature and humidity variations, on the transmission dynamics of diseases like AHS. In our research, we focused on overcoming the challenges associated with identifying key environmental factors and determining the appropriate geographic scale for a comprehensive global understanding of AHS. Our aim was to bridge existing knowledge gaps and elucidate the fundamental principles governing AHS transmission. This study establishes a solid foundation for understanding the intricate dynamics of AHS and offers practical pathways for conservation efforts. It emphasizes the urgent need for environmentally conscious strategies to protect horse populations and the industries dependent on them. By highlighting the relationship between environmental factors, vector presence, and AHS transmission, our research underscores the importance of a holistic approach to disease mitigation. In conclusion, the findings of our study not only contribute to the scientific understanding of AHS but also serve as a guide for policymakers and practitioners in developing effective strategies for disease management and prevention, tailored to the specific environmental conditions and challenges faced in different regions around the world.
Bycatch mitigation of endangered marine life
Authors: García Mireia Villafáfila , Carpio Antonio , Rivas Marga L 
Published: February 2024

ABSTRACTThe fishing gear deployed by fishermen in seas and oceans throughout the world not only captures target species but also unintentionally ensnares non-target species, a phenomenon known as “by-catch”. This unintended capture of marine life can represent significant challenges for the fishing industry, with adverse impacts on both the environment and species such as sea turtles, marine mammals, seabirds and elasmobranchs, which may be injured or even killed. To address this problem, the fishing industry has implemented regulations and mitigation measures. In this literature review, we have examined 389 articles published between 2010 and 2022 that assess the effectiveness of these measures. It has been demonstrated that the most effective measures are ‘pingers’ for marine mammals, ‘TEDs’ (Turtle Excluder Devices) for sea turtles, and ‘BSLs’ (Bird Scaring Lines), more commonly known as ‘tori lines’, for seabirds. The most complex case is that of elasmobranchs, and the most effective measure has yet to be discovered. This complexity arises from the ongoing targeted fishing of these species, resulting in less monitoring of their catches and, therefore, fewer surveys. Overall, we encourage the global implementation of these measures by the fishing industry in order to reduce by-catch in an attempt to ensure the future of many endangered species.
Transient DREADD manipulation of the dorsal Dentate Gyrus in rats impairs disambiguation of similar place-outcome associations
Authors: Lim Judith , Souiki A. , Ahmad P. , Oomen Charlotte A. , Huis in ’t Veld Gerjan , Lansink Carien S. , Pennartz Cyriel M.A. , Olcese Umberto 
Published: February 2024

AbstractThe dentate gyrus subfield of the hippocampus is thought to be critically involved in the disambiguation of similar episodic experiences and places in a context-dependent manner. However, most empirical evidence has come from lesion and gene knock-out studies in rodents, in which the dentate gyrus function is permanently perturbed and compensation of affected functions via other areas within the memory circuit could take place. The acute and causal role of the dentate gyrus herein remains therefore elusive. The present study aimed to investigate the acute role of the dorsal dentate gyrus in disambiguation learning using reversible inhibitory DREADDs.Rats were trained on a location discrimination task and learnt to discriminate between a rewarded and unrewarded location with either small (similar condition) or large (dissimilar condition) separation. Reward contingencies switched after a reversal rule, allowing us to track the temporal engagement of the dentate gyrus during the task. Bilateral but not unilateral DREADD modulation of the dentate gyrus impaired the initial acquisition learning of place-reward associations, but performance rapidly recovered to control levels within the same session. Modelling of the behavioural patterns revealed that reward learning and reward sensitivity were not associated with the DREADD-dependent impairment during acquisition learning, suggesting that either the ability to encode place-reward associations, or the fine-grained coding of place were instead affected. Our study thus provides novel evidence that the dorsal dentate gyrus is acutely and bilaterally engaged during the initial acquisition learning of ambiguous place-reward associations, although the exact neural mechanisms supporting this function still need to be fully understood.
RNA-MobiSeq: Deep mutational scanning and mobility-based selection for RNA structure inference
Authors: Tang Jinle , Shi Yazhou , Zhang Zhe , Luo Dailin , Zhan Jian , Zhou Yaoqi 
Published: February 2024

ABSTRACTTertiary structures of RNAs are increasingly found to be essential for their functions and yet are notoriously challenging to be determined by experimental techniques or predicted by energy-based and AlphaFold2-like deep-learning-based computational methods. Here, we coupled deep mutational scanning with mobility-based selection to separate structurally stable from nonstable RNA variants. The subsequent high-throughput sequencing allows the detection of the covariational signals of key secondary and tertiary base pairs with significantly improved, RNA-specific, unsupervised analysis of covariation-induced deviation of activity (CODA2) and amplification of these signals by Monte-Carlo simulated annealing. The resulting base-pairing structures can serve as the restraints for final energy-based structure predictions. This MobiSeq technique was tested on four structurally different RNAs. The results show that the detection of tertiary base pairs by MobiSeq allows reasonably accurate prediction of RNA tertiary structures. The proposed method should be useful for structural inference and improved mechanistic understanding of all RNAs with detectable changes in mobility due to deleterious mutations.
Improved BOLD Detection with Sliced Inverse Regression
Authors: Lizarraga Andrew , Li Katherine 
Published: February 2024

AbstractFunctional magnetic resonance imaging (fMRI) has been effective in linking task-related brain responses to changes in blood oxygen level density (BOLD). However, its reliance on BOLD measurements makes it vulnerable to artifacts and false-positive signals. Commonly, researchers use many regressors in a General Linear Model to filter true signals, but this adds noise and complicates interpretation. In this paper we suggest using Sliced Inverse Regression (SIR) to simplify covariate dimensionality and identify relevant regressors. We compare a general linear model applied to both original and SIR-adjusted data, demonstrating that SIR improves signal detection, reduces noise, and yields statistically significant results even with conservative measures.
Female GluA3-KO mice show early onset hearing loss and afferent swellings in ambient sound levels
Authors: Pal Indra , Bhattacharyya Atri , V-Ghaffari Babak , Williams Essence D. , Xiao Maolei , Rutherford Mark A. , Rubio María Eulalia 
Published: February 2024

AbstractAMPA-type glutamate receptors (AMPAR) mediate excitatory cochlear transmission. However, the unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 (Gria3KO) in male mice reduced cochlear output by 8-weeks of age. SinceGria3is X-linked and considering sex differences in hearing vulnerability, we hypothesized accelerated presbycusis inGria3KOfemales. Here, auditory brainstem responses (ABR) were similar in 3-week-old femaleGria3WTandGria3KOmice. However, when raised in ambient sound, ABR thresholds were elevated and wave-1 amplitudes were diminished at 5-weeks and older inGria3KO. In contrast, these metrics were similar between genotypes when raised in quiet. Paired synapses were similar in number, but lone ribbons and ribbonless synapses were increased in femaleGria3KOmice in ambient sound compared toGria3WTor to either genotype raised in quiet. Synaptic GluA4:GluA2 ratios increased relative toGria3WT, particularly in ambient sound, suggesting an activity-dependent increase in calcium-permeable AMPARs inGria3KO. Swollen afferent terminals were observed by 5-weeks only inGria3KOfemales reared in ambient sound. We propose that lack of GluA3 induces sex-dependent vulnerability to AMPAR-mediated excitotoxicity.
WITHDRAWN: Assessment of Remediation Through Measuring Nuclear Respiratory Factor 1 (nrf1) Environmental Stressor Transcriptomic Gene Signatures
Authors: Morales Juan , Deoraj Alok , Felty Quentin , Lagos Leonel , Yoo Changwon , Roy Deodutta 
Published: February 2024

Withdrawal StatementThis manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding
Authors: Botova Maiia , Camacho-Zarco Aldo R. , Tognetti Jacqueline , Bessa Luiza Mamigonian , Guseva Serafima , Mikkola Emmi , Salvi Nicola , Maurin Damien , Herrmann Torsten , Blackledge Martin 
Published: February 2024

AbstractThe nucleoprotein (N) of SARS-CoV-2 encapsidates the viral genome and is essential for viral function. The central disordered domain comprises a serine-arginine-rich domain (SR) that is hyperphosphorylated in infected cells. This modification is thought to regulate function of N, although mechanistic details remain unknown. We use time-resolved NMR to follow local and long-range structural changes occurring during hyperphosphorylation by the kinases SRPK1/GSK-3/CK1, thereby identifying a conformational switch that abolishes interaction with RNA. When 8 approximately uniformly-distributed sites are phosphorylated, the SR domain competitively binds the same interface as single-stranded RNA, resulting in RNA binding inhibition. Phosphorylation by PKA does not prevent RNA binding, indicating that the pattern resulting from the physiologically-relevant kinases is specific for inhibition. Long-range contacts between the RNA-binding, linker and dimerization domains are also abrogated, phenomena possibly related to genome packaging and unpackaging. This study provides insight into recruitment of specific host kinases to regulate viral function.
The maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehavioral impairment in mice
Authors: Coley-O’Rourke Elena J. , Lum Gregory R. , Pronovost Geoffrey N. , Özcan Ezgi , Yu Kristie B. , McDermott Janet , Chakhoyan Anna , Goldman Eliza , Vuong Helen E. , Paramo Jorge , Chu Alison , Calkins Kara L. , Hsiao Elaine Y. 
Published: February 2024

AbstractProtein undernutrition is a global risk factor for impaired growth and neurobehavioral development in children. However, the critical periods, environmental interactions, and maternal versus neonatal influences on programming lasting behavioral abnormalities are poorly understood. In a mouse model of fetal growth restriction, limiting maternal protein intake particularly during pregnancy leads to cognitive and anxiety-like behavioral abnormalities in adult offspring, indicating a critical role for the gestational period. By cross-fostering newborn mice to dams previously exposed to either low protein or standard diet, we find that the adult behavioral impairments require diet-induced conditioning of both fetal development and maternal peripartum physiology, rather than either alone. This suggests that protein undernutrition during pregnancy directly disrupts fetal neurodevelopment and indirectly alters maternal state in ways that interact postnatally to precipitate behavioral deficits. Consistent with this, maternal protein restriction during pregnancy reduces the diversity of the maternal gut microbiome, modulates maternal serum metabolomic profiles, and yields widespread alterations in fetal brain transcriptomic and metabolomic profiles, including subsets of microbiome-dependent metabolites. Depletion of the maternal microbiome in protein-restricted dams further alters fetal brain gene expression and exacerbates neurocognitive behavior in adult offspring, suggesting that the maternal microbiome modifies the impact of gestational protein undernutrition on risk for neurobehavioral impairment in the offspring. To explore the potential for microbiome-targeted interventions, we find that maternal treatment with short chain fatty acids or a cocktail of 10 diet- and microbiome-dependent metabolites each yield differential effects on fetal development and/or postnatal behavior. Results from this study highlight impactful prenatal influences of maternal protein undernutrition on fetal neurodevelopment and adverse neurobehavioral trajectories in offspring, which are mitigated by microbiome-targeted interventions during pregnancy.
ProT-Diff: A Modularized and Efficient Approach to De Novo Generation of Antimicrobial Peptide Sequences through Integration of Protein Language Model and Diffusion Model
Authors: Wang Xue-Fei , Tang Jing-Ya , Liang Han , Sun Jing , Dorje Sonam , Peng Bo , Ji Xu-Wo , Li Zhe , Zhang Xian-En , Wang Dian-Bing 
Published: February 2024

AbstractAntimicrobial Peptides (AMPs) represent a promising class of antimicrobial agents crucial for combating antibiotic-resistant pathogens. Despite the emergence of deep learning approaches for AMP discovery, there remains a gap in efficiently generating novel AMPs across various amino acid lengths without prior knowledge of peptide structures or sequence alignments. Here we introduce ProT-Diff, a modularized and efficient deep generative approach that ingeniously combines a pre-trained protein language model with a diffusion model to de novo generate candidate AMP sequences. ProT-Diff enabled the rapid generation of thousands of AMPs with diverse lengths within hours. Following in silico screening based on physicochemical properties and predicted antimicrobial activities, we selected 35 peptides for experimental validation. Remarkably, 34 of these peptides demonstrated antimicrobial activity against Gram-positive or Gram-negative bacteria, with 6 exhibiting broad-spectrum efficacy. Of particular interest, AMP_2, one of the broad-spectrum peptides, displayed potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. Further in vivo assessment revealed its high effectiveness against a clinically relevant drug-resistantE. colistrain in a mouse model of acute peritonitis. This study not only presents a viable generative strategy for novel AMP design but also underscores its potential for generating other functional peptides, thereby broadening the horizon for new drug development.
Deciphering the impact of cancer cell’s secretome and its derived-peptide VGF on breast cancer brain metastasis
Authors: Carvalho Rita , Santos Liliana , Conde Inês , Leitão Ricardo , Ferreira Hugo R. S. , Gomes Célia , Silva Ana Paula , Schmitt Fernando , Carvalho-Maia Carina , Lobo João , Jerónimo Carmen , Paredes Joana , Ribeiro Ana Sofia 
Published: February 2024

AbstractBrain metastases (BM) are one of the most serious clinical problems in breast cancer (BC) progression, associated with lower survival rates and a lack of effective therapies. Thus, to dissect the early stages of the brain metastatic process, we have searched for a brain-tropic metastatic signature on BC cells’ secretome, as a promising source for the discovery of new biomarkers involved in brain metastatic progression.Therefore, six specifically deregulated peptides were found to be enriched in the secretome of brain organotropic BC cells. Importantly, these secretomes caused significant blood-brain barrier (BBB) disruption, as well as microglial activation,in vitroandin vivo. We identified the VGF nerve growth factor inducible as a brain-specific peptide, promoting BBB dysfunction similar to the secretome of brain organotropic BC cells. Concerning microglial activation, a slight increase was also observed upon VGF treatment.In a series of human breast tumors, VGF was found to be expressed in both cancer cells and in the adjacent stroma. VGF-positive tumors showed a significant worse prognosis and were associated with HER2 overexpression and triple-negative molecular signatures. Finally, in a cohort including primary breast tumors and their corresponding metastatic locations to the lung, bone, and brain, we found that VGF significantly correlates with the brain metastatic site.In conclusion, we found a specific BC brain metastatic signature, where VGF was identified as a key mediator in this process. Importantly, its expression was associated with poor prognosis for BC patients, probably due to its associated increased risk of developing BM.
Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons
Authors: Domingues Ana Verónica , Carvalho Tawan T. A. , Martins Gabriela J. , Correia Raquel , Coimbra Bárbara , Gonçalves Ricardo , Wezik Marcelina , Gaspar Rita , Pinto Luísa , Sousa Nuno , Costa Rui M. , Soares-Cunha Carina , Rodrigues Ana João 
Published: February 2024

AbstractThe nucleus accumbens (NAc) is a key brain region for motivated behaviors, yet how distinct neuronal populations encode appetitive or aversive stimuli remains undetermined. Using microendoscopic calcium imaging, we tracked NAc shell D1- or D2-medium spiny neurons’ (MSNs) activity during exposure to stimuli of opposing valence and associative learning. Despite drift in individual neurons’ coding, both D1- and D2-population activity was sufficient to discriminate opposing valence unconditioned stimuli, but not predictive cues. Notably, D1- and D2-MSNs were similarly co-recruited during appetitive and aversive conditioning, supporting a concurrent role in associative learning. Conversely, when contingencies changed, there was an asymmetric response in the NAc, with more pronounced changes in the activity of D2-MSNs. Optogenetic manipulation of D2-MSNs provided causal evidence of the necessity of this population in the extinction of aversive associations.Our results reveal how NAc shell neurons encode valence, Pavlovian associations and their extinction, and unveil new mechanisms underlying motivated behaviors.
Parkinsonism in bipolar disorder: a clinical-neuroimaging study
Authors: Nishio Yoshiyuki , Amemiya Kiyomi , Ohyama Jun 
Published: February 2024

ABSTRACTBackgroundParkinsonism is a frequently encountered symptom in individuals with bipolar disorder (BD). It can be drug-induced, co-occurring with Parkinson’s disease (PD), or a genuine motor abnormality of BD itself. This study aims to clarify the primary pathophysiology of parkinsonism in BD.MethodsSixteen patients with BD and parkinsonism were recruited from consecutive patients who were referred to a neurology clinic at a tertiary psychiatric center. The patients underwent clinical assessments, dopamine transporter single-photon computed tomography (DAT-SPECT), cardiac MIBG scintigraphy, and morphometric MRI. The positivity or negativity of Lewy body disease (LBD) biomarkers was determined based on the visual assessment of DAT-SPECT and heart-to-mediastinum ratio on cardiac MIBG scintigraphy. Four out of the 16 participants received 300-600mg of levodopa.ResultsThirteen patients were diagnosed with BD type 1, and 12 had experienced > 5 previous mood episodes. Parkinsonism developed more than 10 years after the onset of BD and after the age of 50 years in all patients. Four cases were positive for LBD biomarkers. Six patients with negative LBD biomarkers showed reduced striatal uptake with z-scores below -2.0. MRI morphometry revealed varying degrees of brain atrophy in most patients. Three of the 4 patients did not respond to 600mg of levodopa.ConclusionsThis study suggests that the majority of parkinsonism in BD is not due to PD/LBD. Parkinsonism may be a genuine motor abnormality of BD in late life.
Assessing the performance of Laboratory professionals following a day of malaria microscopy training in Kano, Nigeria
Authors: Ayando Oluwaseunayo Deborah , Ravi Nirmal , Obinnaya Okoronkwo Marizu 
Published: February 2024

AbstractMalaria is a global health burden with a projection of 247 million cases in 2021 in 84 countries known to be malaria-endemic. The majority of the cases are expected to occur in WHO African Region countries inclusive of Nigeria where the disease is a public health concern particularly in the northern regions. This study aimed to evaluate the effectiveness of a one-day malaria microscopy training program for laboratory professionals in Kano, Nigeria, and to assess the impact of the training on their proficiency in detecting malaria parasites. A total of 56 medical laboratory professionals from both public and private healthcare facilities participated in the training, which was based on the WHO basic microscopy learners guide. The training included theoretical and practical components, focusing on blood film preparation, staining techniques, and identification of Plasmodium species. Participants’ knowledge was assessed before and after the training using a pre-test and post-test survey, and their proficiency in malaria diagnosis was evaluated through the examination of a panel of stained blood slides. The sensitivity and specificity of the participants in detecting malaria parasites were determined as 66% and 34% respectively, indicating moderate sensitivity but very low specificity. A significant improvement in participants’ knowledge of malaria detection was observed post-training, with private facilities showing a median knowledge score increase from 47.5% to 65.0%, and public facilities from 55.0% to 70.0%. However, the overall agreement between participant readers and an expert reader, measured by the kappa coefficient, was zero, suggesting no agreement beyond chance. The study highlighted the need for enhanced training and standardization in malaria microscopy to improve diagnostic accuracy. Despite the moderate increase in knowledge and sensitivity post-training, the low specificity and agreement underscore the importance of ongoing education and quality assurance measures in malaria diagnosis, especially in high-prevalence settings like Kano.