bluuebunny/crossref_metadata_2025_split huggingface dataset:
Junctional Adhesion Molecule (JAM)-C recruitment of Pard3 and drebrin to cell contacts initiates neuron-glia recognition and layer-specific cell sorting in developing cerebella
Authors: Hallada Liam P. , Shirinifard Abbas , Solecki David J 
Published: March 2024

AbstractSorting maturing neurons into distinct layers is critical for brain development, with disruptions leading to neurological disorders and pediatric cancers. Lamination coordinates where, when, and how cells interact, facilitating events that direct migrating neurons to their destined positions within emerging neural networks and control the wiring of connections in functional circuits. While the role of adhesion molecule expression and presentation in driving adhesive recognition during neuronal migration along glial fibers is recognized, the mechanisms by which the spatial arrangement of these molecules on the cell surface dictates adhesive specificity and translates contact-based external cues into intracellular responses like polarization and cytoskeletal organization remain largely unexplored. We used the cerebellar granule neuron (CGN) system to demonstrate that JAM-C receptor cis-binding on the same cell and trans-binding to neighboring cells controls the recruitment of the Pard3 polarity protein and drebrin microtubule-actin crosslinker at CGN to glial adhesion sites, complementing previous studies that showed Pard3 controls JAM-C exocytic surface presentation. Leveraging advanced imaging techniques, specific probes for cell recognition, and analytical methods to dissect adhesion dynamics, our findings reveal: 1) JAM-C cis or trans mutants result in reduced adhesion formation between CGNs and cerebellar glia, 2) these mutants exhibit delayed recruitment of Pard3 at the adhesion sites, and 3) CGNs with JAM-C mutations experience postponed sorting and entry into the cerebellar molecular layer (ML). By developing a conditional system to image adhesion components from two different cells simultaneously, we made it possible to investigate the dynamics of cell recognition on both sides of neuron-glial contacts and the subsequent recruitment of proteins required for CGN migration. This system and an approach that calculates local correlation based on convolution kernels at the cell adhesions site revealed that CGN to CGN JAM recognition preferentially recruits higher levels of Pard3 and drebrin than CGN to glia JAM recognition. The long latency time of CGNs in the inner external germinal layer (EGL) can be attributed to the combined strength of CGN-CGN contacts and the less efficient Pard3 recruitment by CGN-BG contacts, acting as gatekeepers to ML entry. As CGNs eventually transition to glia binding for radial migration, our research demonstrates that establishing permissive JAM-recognition sites on glia via cis and trans interactions of CGN JAM-C serves as a critical temporal checkpoint for sorting at the EGL to ML boundary. This mechanism integrates intrinsic and extrinsic cellular signals, facilitating heterotypic cell sorting into the ML and dictating the precise spatial organization within the cerebellar architecture.Graphical Abstract
Maternal characteristics and their relation to early mother-child interaction and cognitive development in toddlers
Authors: Preiß Jasmin , Lang Adelheid , Hauser Theresa , Angerer Monika , Schernhardt Peter , Schabus Manuel 
Published: March 2024

AbstractEarly mother-infant interaction is believed to have a significant impact on the social, cognitive, and emotional development of children. These interactions are not only influenced by child and contextual factors but also by the mother’s personality traits and strain. In this study, we investigated the relation between maternal factors such as personality, depressive symptoms, or experiencing of emotions, with (i) children’s early cognitive development and (ii) interaction patterns in a sample of 116 mother-child dyads (mean child age = 18.63 months ± 6.42). Maternal factors were assessed using standardized questionnaires, children’s cognitive development was measured using the Bayley Scales of Infant and Toddler Development, and interaction patterns were evaluated using the CARE-Index. The study found that children of mothers who scored higher in agreeableness performed better in cognitive assessments. Additionally, our analysis revealed statistical trends indicating that mothers with higher levels of conscientiousness tended to be less unresponsive in the interaction with their infants, while those with higher levels of neuroticism were more likely to exhibit compulsive behavior in their toddlers. Additionally, there was a trend indicating that maternal depression was associated with increased maternal controlling behavior towards toddlers. Finally, mothers who placed significant importance on their bodily signals to assess their overall well-being had higher scores in the quality of interaction with their child. Overall, these findings show the intricate relation between maternal behavior and state with dyadic interaction quality. This should underline that optimal infant development is only possible if mothers are well supported especially if in need due to various burdens such as depressive symptoms.
Harnessing the Power of Large Language Models (LLMs) to Unravel the Influence of Genes and Medication on Biological Processes of Wound Healing*
Authors: Jui Jayati H. , Hauskrecht Milos 
Published: March 2024

AbstractRecent advancements in Large Language Models (LLMs) have ushered in a new era for knowledge extraction in the domains of biological and clinical natural language processing (NLP). In this research, we present a novel approach to understanding the regulatory effects of genes and medications on biological processes central to wound healing. Utilizing the capabilities of Generative Pre-trained Transformer (GPT) models by OpenAI, specifically GPT-3.5 and GPT-4, we developed a comprehensive pipeline for the identification and grounding of biological processes and the extraction of such regulatory relations. The performances of both GPTs were rigorously evaluated against a manually annotated corpus of 104 PubMed titles, focusing on their ability to accurately identify and ground biological process concepts and extract relevant regulatory relationships from the text. Our findings demonstrate that GPT-4, in particular, exhibits superior performance in all the tasks, showcasing its potential to facilitate significant advancements in biomedical research without requiring model fine-tuning.
Probing enzyme-dependent pseudouridylation using direct RNA sequencing to assess neuronal epitranscriptome plasticity
Authors: Fanari Oleksandra , Tavakoli Sepideh , Qiu Yuchen , Makhamreh Amr , Nian Keqing , Akeson Stuart , Meseonznik Michele , McCormick Caroline A. , Bloch Dylan , Gamper Howard , Jain Miten , Hou Ya-Ming , Wanunu Meni , Rouhanifard Sara H. 
Published: March 2024

SummaryChemical modifications in mRNAs, such as pseudouridine (psi), can control gene expression. Yet, we know little about how they are regulated, especially in neurons. We applied nanopore direct RNA sequencing to investigate psi dynamics in SH-SY5Y cells in response to two perturbations that model a natural and unnatural cellular state: retinoic-acid-mediated differentiation (healthy) and exposure to the neurotoxicant, lead (unhealthy). We discovered that the expression of some psi writers change significantly in response to physiological conditions. We also found that globally, lead-treated cells have more psi sites but lower relative occupancy than untreated cells and differentiated cells. Interestingly, examples of highly plastic sites were accompanied by constant expression for psi writers, suggesting trans-regulation. Many positions were static throughout all three cellular states, suggestive of a “housekeeping” function. This study enables investigations into mechanisms that control psi modifications in neurons and its possible protective effects in response to cellular stress.
Differential Non-Coding RNA Profiles for Lung Cancer Early Detection in African and White Americans
Authors: Gao Lu , Dhilipkannah Pushpa , Holden Van K , Deepak Janaki , Sachdeva Ashutosh , Todd Nevins W , Stass Sanford A , Jiang Feng 
Published: March 2024

AbstractIntroductionLung cancer leads in cancer-related deaths. Disparities are observed in lung cancer rates, with African Americans (AAs) experiencing disproportionately higher incidence and mortality compared to other ethnic groups. Non-coding RNAs (ncRNAs) play crucial roles in lung tumorigenesis. Our objective was to identify ncRNA biomarkers associated with the racial disparity in lung cancer.MethodsUsing droplet digital PCR, we examined 93 lung-cancer-associated ncRNAs in the plasma and sputum samples from AA and White American (WA) participants, which included 118 patients and 92 cancer-free smokers. Subsequently, we validated our results with a separate cohort comprising 56 cases and 72 controls.ResultsIn the AA population, plasma showed differential expression of ten ncRNAs, while sputum revealed four ncRNAs when comparing lung cancer patients to the control group. In the WA population, the plasma displayed eleven ncRNAs, and the sputum had five ncRNAs showing differential expression between the lung cancer patients and the control group. For AAs, we identified a three-ncRNA panel (plasma miRs-147b, 324-3p, 422a) diagnosing lung cancer in AAs with 86% sensitivity and 89% specificity. For WAs, a four-ncRNA panel was developed, comprising sputum miR-34a-5p and plasma miRs-103-3p, 126-3p, 205-5p, achieving 88% sensitivity and 87% specificity. These panels remained effective across different stages and histological types of lung tumors and were validated in the independent cohort.ConclusionsThe ethnicity-related ncRNA signatures have promise as biomarkers to address the racial disparity in lung cancer.
Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis
Authors: Ferrière-Steinert Santiago , Jiménez Joaquín Valenzuela , Araya Sebastián Heskia , Carvajal Thomas Kouyoumdjian , Ramos-Rojas José , Gajardo Abraham I. J. 
Published: March 2024

AbstractBackgroundSepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting.This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction.MethodsWe will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences.DiscussionThis study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment.Conclusion about the certainty of evidence will be presented in a ‘Summary of finding’ table.PROSPERO registration:(CRD42024468883)
Evaluating Magnetic Stimulation as an Innovative Approach for Treating Dry Eye Syndrome: Safety and Efficacy Initial study
Authors: Ben-Eli Hadas , Perelman Shimon , Wajnsztajn Denise , Solomon Abraham 
Published: March 2024

AbstractObjectiveThe objective of this study was to assess the safety and preliminary efficacy of repetitive magnetic stimulation (RMS) as an intervention for dry eye syndrome, focusing on symptom reduction.MethodologyThis investigation involved 22 adult participants diagnosed with moderate to severe dry eye syndrome. These individuals were subjected to RMS treatment targeting one or both eyes using the VIVEYE - Ocular Magnetic Neurostimulation System Ver 1.0 (Epitech-Mag LTD; NIH clinical trials registry #NCT03012698). A placebo-controlled group was also included for comparative analysis, with all subjects being monitored over a three-month period. The evaluation of safety encompassed monitoring changes in best corrected visual acuity, ocular pathology, and reporting of adverse events. Participant tolerance was gauged through questionnaires, measurements of intraocular pressure (IOP), Schirmer’s test, and vital signs. The efficacy of the treatment was assessed by comparing pre- and post-treatment scores on fluorescein staining (according to the National Eye Institute (NEI) grading) and patient-reported outcomes.ResultsThe study found no significant changes in visual acuity, IOP, or Schirmer’s test results between the RMS-treated and control groups (p<0.05), indicating RMS does not adversely affect these ocular functions. However, RMS treatment was associated with improved tear film stability (p=0.198 vs. p=0.045) and corneal health (p=0.52 vs. p=0.004), with no improvements in the control group. Initial symptom improvement was observed in both RMS-treated and placebo groups (p=0.007 vs p=0.008), suggesting RMS’s potential for treating ocular surface conditions.ConclusionThe findings of this study introduce repetitive magnetic stimulation (RMS) as a promising therapeutic option for dry eye syndrome, demonstrating its capability to promote corneal epithelium repair, enhance tear film stability, and improve subjective symptom evaluations without adversely affecting intraocular pressure, visual acuity, or tear production. This confirms the safety and suggests the efficacy of RMS therapy for dry eye conditions.
Distinct Motor Map Characteristics for Biceps and Triceps Muscles in Persons with Chronic Tetraplegia: Implications for Arm Function
Authors: Liu Jia , O’laughlin Kyle , Forrest Gail F. , Arora Tarun , Nemunaitis Gregory , Cunningham David , Kirshblum Steven , Pundik Svetlana , Baker Kelsey , Bryden Anne , Kilgore Kevin , Bethoux Francois , Wang Xiaofeng , Henzel M. Kristi , Brihmat Nabila , Bayram Mehmed Bugrahan , Plow Ela B. 
Published: March 2024

AbstractFollowing spinal cord injury (SCI), intact neural resources undergo widespread reorganization within the brain. Animal models reveal motor cortical representations devoted to spared muscles above injury expand at the expense of territories occupied by weaker muscles. In this study, we investigated whether motor representations are similarly reorganized between a relatively spared biceps muscle and a weakened triceps muscle in persons with chronic tetraplegia following traumatic cervical SCI in association with upper limb motor function. Twenty-four adults with cervical SCI and 15 able-bodied participants underwent motor mapping using transcranial magnetic stimulation. We determined following map characteristics: area, amplitude (maximal motor evoked potential and volume), and center of gravity. Maximal voluntary contraction (MVC) and motor function (Capabilities of the Upper Extremity Test or CUE-T) were also assessed. Findings reveal that participants with SCI had hyper-excitable biceps maps than triceps, and hyper-excitable biceps maps also compared to biceps maps in able-bodied participants. Higher amplitude of biceps and triceps maps was associated with better motor function (higher CUE-T) and more distal injury (i.e., more spared segments) in persons with SCI. Amplitudes of biceps but not the triceps maps were associated with higher muscle MVCs. In conclusion, over-excitable biceps than triceps map in SCI may represent deafferentation plasticity. For the first time, we demonstrate how map reorganization of spared and weaker muscles in persons with chronic cervical SCI is associated with upper limb motor status. Use-dependent mechanisms may shift neural balance in favor of spared muscles, supporting potential use as response biomarkers in rehabilitation studies.New & NoteworthyOur study reports evidence in humans with cervical SCI that motor representation for the relatively spared muscle becomes hyper-excitable compared to that for the weaker muscle to the extent that hyper-excitability is even higher compared to biceps maps in uninjured individuals. Use-dependent mechanisms likely favor such heightened excitability of spared maps. For the first time, we demonstrate clinical relevance of map excitability in humans with SCI, supporting potential use as a biomarker of recovery.
The Role of Morphological Adaptability inVibrio cholerae’s Motility and Pathogenicity
Authors: Xu Jun , Abe Keigo , Kodama Toshio , Sultana Marzia , Chac Denise , Markiewicz Susan M. , Kuba Erika , Tsunoda Shiyu , Alam Munirul , Weil Ana A. , Nakamura Shuichi , Yamashiro Tetsu 
Published: March 2024

ABSTRACTVibrio cholerae, the etiological agent of cholera, exhibits remarkable adaptability to different environmental conditions by undergoing morphological changes that significantly contribute to its pathogenicity and impact the epidemiology of the disease globally. This study investigates the morphological adaptability of the clinically isolatedV. choleraeO1 strain, specifically focusing on the motility and pathogenicity differences between the filamentous and original comma-shaped forms within diverse viscosity conditions. Utilizing the El Tor strain ofV. choleraeO1, we induced the transformation into the filamentous form and performed a comparative analysis with the canonical comma-shaped morphology. Our approach involved assessing motility patterns, swimming speeds, rotation rates, kinematics, and reversal frequencies through dark-field microscopy and high-speed imaging techniques. The findings reveal that filamentousV. choleraecell retains enhanced motility in viscous environments. This suggests an evolutionary adaptation enabling survival across a range of habitats, notably the human gastrointestinal tract. Filamentous forms demonstrated increased reversal behavior at mucin interfaces, hinting at an advantage in penetrating the mucus layer. Rabbit intestinal loop assays further showed that both morphological forms exhibit similar fluid accumulation ratios, thus indicating comparable pathogenic potentials. These results underscore the significance ofV. cholerae’s morphological flexibility in adapting to environmental viscosity changes, shedding light on the bacterium’s intricate survival and infection strategies. Our study provides critical insights into the dynamics of cholera, underlining the importance of considering bacterial morphology in developing effective cholera control strategies.
Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes
Authors: Bitria Laura Mora , Debebe Bisrat J. , Miners Kelly , Ladell Kristin , Kaur Charandeep , Traherne James A. , Jiang Wei , Hadcocks Linda , McQuibban Nicholas A.R. , Trowsdale John , Wong F Susan , Pontikos Nikolas , Niederalt Christoph , Asquith Becca 
Published: March 2024

AbstractInhibitory killer cell immunoglobulin-like receptors (iKIRs) are a family of inhibitory receptors that are expressed by natural killer cells and late-stage differentiated T cells. There is accumulating evidence that iKIRs regulate T cell-mediated immunity. Recently, we reported that T cell-mediated control was enhanced by iKIRs in chronic viral infections. We hypothesized that in the context of autoimmunity, where an enhanced T cell response might be considered detrimental, iKIRs would have an opposite effect. We studied Type 1 diabetes (T1D) as a paradigmatic example of autoimmunity. In T1D, variation in the Human Leucocyte Antigen (HLA) genes explains up to 50% of the genetic risk, indicating that T cells have a major role in T1D etiopathogenesis. To investigate if iKIRs affect this T cell response we asked whether HLA associations were modified by iKIR genes. We conducted an immunogenetic analysis of a case-control T1D dataset (N= 11,961) and found that iKIR genes, in the presence of genes encoding their ligands, have a consistent and significant effect on protective HLA class II genetic associations. Our results were validated in an independent data set. We conclude that iKIRs significantly decrease HLA class II protective associations and suggest that iKIRs regulate CD4+ T cell responses in T1D.
Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish
Authors: de Sousa Eveline Bezerra , Heymbeeck João Alphonse Apóstolo , Feitosa Leonardo Miranda , Xavier Amanda Gabriele Oliveira , Campos Kimberly dos Santos , dos Santos Rodrigues Lais do Socorro , de Freitas Larissa Mota , do Carmo Silva Rhayra Xavier , Ikeda Saulo Rivera , Silva Suellen de Nazaré dos Santos , Rocha Sueslene Prado , do Nascimento Wilker Leite , Moraes Edinaldo Rogério da Silva , Leão Luana Ketlen Reis , Herculano Anderson Manoel , Maximino Caio , Pereira Antonio , Lima-Maximino Monica 
Published: March 2024

AbstractNitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in time-dependent sensitization, a behavioral model of translational relevance to trauma and stress-related disorders, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents TDS; blocking NOS-2 90 min after stress also prevents TDS, as does blocking calcium-activated potassium channels in this latter time window. TDS is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce TDS.