bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult expression of the cell adhesion protein Fasciclin 3 is required for the maintenance of adult olfactory interneurons
Authors: Chithran Aarya Vaikakkara , Allan Douglas W. , O’Connor Timothy P. 
Published: March 2024

ABSTRACTThe proper functioning of the nervous system is dependent on the establishment and maintenance of intricate networks of neurons that form functional neural circuits. Once neural circuits are assembled during development, a distinct set of molecular programs is likely required to maintain their connectivity throughout the lifetime of the organism. Here, we demonstrate that Fasciclin 3 (Fas3), an axon guidance cell adhesion protein, is necessary for the maintenance of the olfactory circuit in adultDrosophila. We utilized the TARGET system to spatiotemporally knockdownFas3in selected populations of adult neurons. Our findings show thatFas3knockdown results in the death of olfactory circuit neurons and reduced survival of adults. We also demonstrated thatFas3knockdown activates caspase-3 mediated cell death in olfactory local interneurons, which can be rescued by overexpressing p35, an anti-apoptotic protein. This work adds to the growing set of evidence indicating a critical role for axon guidance proteins in the maintenance of neuronal circuits in adults.SUMMARY STATEMENTLittle is known about the maintenance of adult neural circuits. We show that the continuous expression of Fasciclin 3, a cell adhesion protein involved in axon guidance, is required for neuronal survival in the adult olfactory circuit.
Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer
Authors: Chen Kai-En , Tillu Vikas A. , Gopaldass Navin , Chowdhury Sudeshna Roy , Leneva Natalya , Kovtun Oleksiy , Ruan Juanfang , Guo Qian , Ariotti Nicholas , Mayer Andreas , Collins Brett M. 
Published: March 2024

ABSTRACTRetromer mediates endosomal retrieval of transmembrane proteins in all eukaryotes and was first discovered in yeast in complex with the Vps5 and Vps17 sorting nexins (SNXs). Cryoelectron tomography (cryoET) studies of Retromer–Vps5 revealed a pseudo-helical coat on membrane tubules where dimers of the Vps26 subunit bind Vps5 membrane-proximal domains. However, the Vps29 subunit is also required for Vps5–Vps17 association despite being far from the membrane. Here, we show that Vps5 binds both Vps29 and Vps35 subunits through its unstructured N-terminal domain. A Pro-Leu (PL) motif in Vps5 binds Vps29 and is required for association with Retromer on membrane tubulesin vitro, and for the proper recycling of the Vps10 cargo inSaccharomyces cerevisiae. CryoET of Retromer tubules with Vps5–Vps17 heterodimers show a similar architecture to the coat with Vps5–Vps5 homodimers, however, the spatial relationship between Retromer units is highly restricted, likely due to more limited orientations for docking. These results provide new mechanistic insights into how Retromer and SNX-BAR association has evolved across species.
Transforming spontaneous premature neonatal EEG to unpaired spontaneous fetal MEG using a CycleGan learning approach
Authors: Gallard Alban , Brebion Benoit , Sippel Katrin , Zaylaa Amer , Preissl Hubert , Moghimi Sahar , Fregier Yael , Wallois Fabrice 
Published: March 2024

AbstractA large body of electroencephalography (EEG) studies has characterized the spontaneous neural activity of premature neonates at different gestational ages. However, evaluation of normal and pathological fetal brain development is still a challenge due to the complexity of the extraction and analysis of fetal neural activity. Fetal magnetoencephalography (fMEG) is currently the only available technique to record fetal neural activity with a time resolution equivalent to that of EEG. However, the signatures and characteristics of fetal spontaneous neural activity are still largely unknown. Benefiting from progress in machine learning and artificial intelligence, we aimed to transfer premature EEG to fMEG, to characterize the manifestation of spontaneous activity using the knowledge obtained from premature EEG.In this study, 30 high-resolution EEG recordings from premature newborns and 44 fMEG recordings, both from 34 to 37 weeks of gestation (wGA) were used to develop a transfer function to predict the spontaneous neural activity of the fetus. After preprocessing, bursts of spontaneous activity were detected using the non-linear energy operator over both EEG and fMEG signals. Next, we proposed a CycleGAN-based model to transform the premature EEG to fMEG and vice versa and evaluated its performance with both time and frequency measurements on both forward and inverse conversions.In the time domain, the values were similar for the mean square error (< 5%) and correlation (0.91 ± 0.05 and 0.89 ± 0.08) for the EEG to fMEG and fMEG to EEG transformations between the original data and that generated by CycleGAN. However, considering the frequency content, the CycleGAN-based model modulated the frequency content of EEG to MEG transformed signals relative to the original signals by increasing the power, on average, in all frequency bands, except for the slow delta frequency band. Our developed model showed promising potential to generate a priori signatures of fMEG manifestations related to spontaneous neural activity. Collectively, this study represents the first steps toward identifying neurobiomarkers of fetal brain development.
A Set of Diagnostic Tests for Detection of ActiveBabesia duncaniInfection
Authors: Chand Meenal , Vydyam Pratap , Pal Anasuya C. , Thekkiniath Jose , Darif Dounia , Li Zeng , Choi Jae-Yeon , Magni Ruben , Luchini Alessandra , Tonnetti Laura , Horn Elizabeth J , Tufts Danielle M , Ben Mamoun Choukri 
Published: March 2024

ABSTRACTHuman babesiosis is a rapidly emerging and potentially fatal tick-borne disease caused by intraerythrocytic apicomplexan parasites of theBabesiagenus. Among the various species ofBabesiathat infect humans,B. duncanihas been found to cause severe and life-threatening infections. Detection of activeB. duncaniinfection is critical for accurate diagnosis and effective management of the disease. While molecular assays for the detection ofB. duncaniinfection in blood are available, a reliable strategy to detect biomarkers of active infection has not yet been developed. Here, we report the development of the firstB. duncaniantigen capture assays that rely on the detection of twoB. duncani-exported immunodominant antigens, BdV234 and BdV38. The assays were validated using blood samples from cultured parasites in human erythrocytes andB. duncani-infected laboratory mice at different parasitemia levels and following therapy. The assays display high specificity with no cross-reactivity withB. microti,B. divergens,BabesiaMO1, orP. falciparum.The assay also demonstrates high sensitivity, detecting as low as 115 infected erythrocytes/µl of blood. Screening of 1,731 blood samples from diverse biorepositories, including previously identified Lyme and/orB. microtipositive human samples and new specimens from field mice, showed no evidence ofB. duncaniinfection in these samples. The assays could be useful in diverse diagnostic scenarios, including point-of-care testing for earlyB. duncaniinfection detection in patients, field tests for screening reservoir hosts, and high-throughput screening such as blood collected for transfusion.Short summaryWe developed two ELISA-based assays, BdACA38 and BdACA234, for detectingB. duncani, a potentially fatal tick-borne parasite causing human babesiosis. The assays target two immunodominant antigens, BdV234 and BdV38, demonstrating high specificity (no cross-reactivity with otherBabesiaspecies orPlasmodium falciparum) and sensitivity (detecting as low as 115 infected erythrocytes/µl). The assays were validated using in vitro-cultured parasites and infected mice. Screening diverse blood samples showed no evidence ofB. duncaniactive infection among 1,731 human and field mice blood samples collected from the north-eastern, midwestern, and western US. These assays offer potential in diverse diagnostic scenarios, including early patient detection, reservoir animal screening, and transfusion-transmitted babesiosis prevention.
Similar effect of lidocaine and saline on ciliary beating of nasal epithelial cells in vitro
Authors: Savas Sibel T , Tschanz Stefan A , Latzin Philipp , Casaulta Carmen , Müller Loretta 
Published: March 2024

AbstractRationalePrimary ciliary dyskinesia is a rare genetic disease affecting ciliary motility and causing respiratory symptoms. Diagnosis can be done by high-speed- videomicroscopy using nasal epithelial cells (NECs) obtained via brushings. This procedure can be painful, especially for children. The use of lidocaine is proposed to reduce this pain; however, it is not clear whether lidocaine changes ciliary beating frequency (CBF) or pattern (CBP) in the subsequent high-speed-videomicroscopy.ObjectiveThe aim of this study was to analyse the effect of lidocaine on the CBF and the CBP of differentiated, air-liquid-interface cultured NECs.MethodsNECs from healthy volunteers were obtained via brushings and cultured at the air-liquid-interface. After differentiation, lidocaine or isotonic saline (IS, control) were added apically for 1 or 5 min each and CBF (in top view of whole inserts and side views of scratched cells) and CBP (only side view) were assessed and recorded up to 150 min. CBF was computed and CBP was analysed semiquantitatively.ResultsLidocaine as well as IS increased the CBF in the top view approach significantly compared to baseline. However, we found no significant differences between lidocaine and IS (control) treatment. Additionally, no effect of lidocaine on CBF, CBP, amplitude, inter- and intracellular coordination or transport was seen in the side view approach.
Differences in COVID-19 Vaccination and Experiences among Patients with Hypertension in Colombia and Jamaica during the COVID-19 Pandemic
Authors: Duncan Jacqueline P , Geng Siyi , Lindsay Carene , Ferguson Trevor , Mills Katherine , Lopez-Lopez Jose Patricio , He Hua , Lanza Paola , Williams Makeda , Tutse-Tonwe Veronica , Reyes Mabel , Campo Alfonso , Marshall Allison , Lopez-Jaramillo Patricio , Tulloch-Reid Marshall K 
Published: March 2024

AbstractBackgroundCOVID-19 vaccination and shielding targeted hypertensive patients in low and middle income countries. We describe the COVID-19 experiences of hypertensive patients in Colombia and Jamaica and discuss factors associated with vaccine acceptance.MethodsA cross-sectional study was conducted between December 2021 and February 2022 in 4 randomly selected primary care clinics in Colombia and 10 primary care clinics in Jamaica. Participants in Colombia were randomly selected from an electronic medical record. In Jamaica consecutive participants were selected on clinic days for non-communicable diseases. Interviewer-administered questionnaires were conducted by telephone.Results576 participants were recruited (50% Jamaica; 68.5% female). Jamaica’s participants were younger (36% vs 23% <60 years) and had a lower proportion of persons with “more than high school” education (17.2% vs 30.3%, p=0.011). Colombia’s participants more commonly tested positive for COVID-19 (24.2% vs 6.3%, p<0.001), had a family member or close friend test positive for COVID-19 (54.5% vs, 21.6%; p<0.001), experienced loss of a family member or friend due to COVID-19 (21.5% vs 7.8%, p<0.001) and had vaccination against COVID-19 (90.6% vs 46.7%, p<0.001). Fear of COVID-19 (AOR 2.71, 95% CI 1.20-6.13) and residence in Colombia (AOR 5.88 (95% CI 2.38-14.56) were associated with COVID-19 vaccination. Disruption in health services affecting prescription of medication or access to doctors was low (<10%) for both countries.ConclusionHealth services disruption was low but COVID-19 experiences such as fear of COVID-19 and vaccine acceptance differed significantly between Colombia and Jamaica. Addressing reasons for these differences are important for future pandemic responses.
Biomarker potential of vitreous microRNA in retinal disease: a meta-analysis
Authors: Joseph Diana , Grover Brian , Telias Michael 
Published: March 2024

AbstractBackgroundAcquired retinal diseases such as proliferative diabetic retinopathy and age-related macular degeneration pose significant challenges in diagnosis and prognosis. The vitreous fluid, situated in the posterior chamber of the eye behind the lens, holds a close relationship with the inner retina. Within this milieu, retinal cells secrete a diverse array of biomolecules, potentially harboring vital biomarkers. Among these, short, non-coding micro-RNAs (miRNAs) emerge as promising candidates. Their dynamic regulation by various gene signaling mechanisms, enhanced resistance to degradation, and secretion via separate exocytotic pathways make them particularly significant. Alterations in vitreal miRNA profiles may reflect pathological states and offer insights into disease etiology and progression.AbstractWe conducted a comprehensive meta-analysis of 22 peer-reviewed studies to assess the potential of vitreous miRNAs as biomarkers for retinal diseases. Our analysis demonstrates the potential utility of miRNAs as biomarkers in specific retinal pathologies. We show that miR-142, miR-9, and miR-21 emerge as robust biomarker candidates, displaying consistent and significant alterations correlating with proliferative vitreoretinal diseases. We also address the methodological challenges encountered in characterizing vitreous miRNA content, including the absence of standardized purification, amplification, and analysis protocols, as well as the scarcity of true control samples. Moreover, we make the case for the adoption of specific housekeeping genes and data normalization techniques to standardize miRNA analysis in the vitreous and explore potential methodologies for obtaining vitreous samples from healthy individuals.ConclusionVitreous miRNAs hold promise as potential biomarkers for various retinal diseases, with miR-142, miR-9, and miR-21 emerging as particularly promising candidates. Enhancing methodologies for vitreous sampling and miRNA analysis presents an opportunity to expand the repertoire and utility of miRNA biomarkers in retinal disease diagnosis and prognosis.Graphic abstractFrom left to right, the diagram shows the location of the retina and the vitreous humor within the eye; the microanatomy of the retinal layers showcasing the secretion of exosomes and biomolecules into the vitreous from its anterior side (inner retinal layers); a magnified illustration of miRNA secretion process from gene expression in the cell nucleus to exosome -dependent and - independent secretion pathways; and the process of intravitreal biopsy for collection and analysis of miRNA expression using quantitative PCR methods.
A Novel Digital Twin Strategy to Examine the Implications of Randomized Clinical Trials for Real-World Populations
Authors: Thangaraj Phyllis M. , Shankar Sumukh Vasisht , Huang Sicong , Nadkarni Girish N. , Mortazavi Bobak J. , Oikonomou Evangelos K. , Khera Rohan 
Published: March 2024

ABSTRACTRandomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. We developed a statistically informed Generative Adversarial Network (GAN) model, RCT-Twin-GAN, that leverages relationships between covariates and outcomes and generates a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population. We used RCT-Twin-GAN to reproduce treatment effect outcomes of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial, which tested the same intervention but found different treatment effects. To demonstrate treatment effect estimates of each RCT conditioned on the other RCT’s patient population, we evaluated the cardiovascular event-free survival of SPRINT digital twins conditioned on the ACCORD cohort and vice versa (ACCORD twins conditioned on SPRINT). The conditioned digital twins were balanced across intervention and control arms (mean absolute standardized mean difference (MASMD) of covariates between treatment arms 0.019 (SD 0.018), and the conditioned covariates of the SPRINT-Twin on ACCORD were more similar to ACCORD than SPRINT (MASMD 0.0082 SD 0.016 vs. 0.46 SD 0.20). Notably, across iterations, SPRINT conditioned ACCORD-Twin datasets reproduced the overall non-significant effect size seen in ACCORD (5-year cardiovascular outcome hazard ratio (95% confidence interval) of 0.88 (0.73-1.06) in ACCORD vs. median 0.87 (0.68-1.13) in the SPRINT conditioned ACCORD-Twin), while the ACCORD conditioned SPRINT-Twins reproduced the significant effect size seen in SPRINT (0.75 (0.64-0.89) vs. median 0.79 (0.72-0.86)) in the ACCORD conditioned SPRINT-Twin). Finally, we demonstrate the translation of this approach to real-world populations by conditioning the trials on an electronic health record population. Therefore, RCT-Twin-GAN simulates the direct translation of RCT-derived treatment effects across various patient populations.
Gag proteins encoded by endogenous retroviruses are required for zebrafish development
Authors: Chang Ni-Chen , Wells Jonathan N. , Wang Andrew Y. , Schofield Phillip , Huang Yi-Chia , Truong Vinh H. , Simoes-Costa Marcos , Feschotte Cédric 
Published: March 2024

AbstractTransposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an “addiction” model to explain how active TEs can be integrated into conserved developmental processes.
Microtubule-based nucleation results in a large sensitivity to cell geometry of the plant cortical array
Authors: Saltini Marco , Deinum Eva E. 
Published: March 2024

AbstractMany plant cell functions, including cell morphogenesis and anisotropic growth, rely on the self-organisation of cortical microtubules into aligned arrays with the correct orientation. An important ongoing debate is how cell geometry, wall mechanical stresses, and other internal and external cues are integrated to determine the orientation of the cortical array. Here, we demonstrate that microtubule-based nucleation can markedly shift the balance between these often competing forces. For this, we developed a novel, more realistic model for microtubule-based nucleation in the simulation platform CorticalSim, which avoids the longstanding inhomogeneity problem stemming from previous, less realistic models for microtubule-based nucleation. We show that microtubule-based nucleation increases the sensitivity of the array to cell geometry, extending the regime of spontaneous alignment compared to isotropic nucleation. In the case of cylindrical cell shapes, we show that this translates in a strong tendency to align in the transverse direction rather than along the vertical axis, and this is robust against small directional cues in the longitudinal direction. Our model provides a powerful tool for investigating how plant cells integrate multiple biases to orient their cortical arrays, offering new insights into the biophysical mechanisms underlying cell shape and growth.
State-dependent Online Reactivations for Different Learning Strategies in Foraging
Authors: Son Sangkyu , Wang Maya Zhe , Hayden Benjamin Y. , Yoo Seng Bum Michael 
Published: March 2024

SUMMARYReactivation of neural responses associated with navigation is thought to facilitate learning. We wondered whether reactivation is subject to contextual control, meaning that different types of learning promote different reactivation patterns. We trained macaques to forage in a first-person virtual maze and identified two distinct learning states prioritizing reward and information using unsupervised ethogramming based on low-level features. In orbitofrontal (OFC) and retrosplenial (RSC) cortices, representations of the goal, the path towards it, and recently traveled paths were strongly reactivated - online - during reward-prioritizing choices. During learning, reactivation of optimal paths increased in RSC after reward-prioritizing choices, and reactivation of uninformative paths decreased in RSC and OFC after information-prioritizing choices. Reactivation in OFC selectively covaried with ongoing RSC activity when prioritizing information; vice versa during prioritizing reward. These results highlight that cognitive states can drive learning and reactivation patterns can be tailored to the needs of the moment.
A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth
Authors: Saunders Harriet A. J. , van den Berg Cyntha M. , Hoogebeen Robin , Schweizer Donna , Stecker Kelly E. , Roepman Ronald , Howes Stuart C. , Akhmanova Anna 
Published: March 2024

AbstractCilia are essential motile or sensory organelles found on many eukaryotic cells. Their formation and function rely on axonemal microtubules, which exhibit very slow dynamics, however the underlying biochemical mechanisms are largely unexplored. Here, we reconstitutedin vitrothe individual and collective activities of the ciliary tip module proteins, CEP104, CSPP1, TOGARAM1, ARMC9 and CCDC66, which interact with each other and with microtubules, and, when mutated, cause ciliopathies such as Joubert syndrome. CEP104, a protein containing a tubulin-binding TOG domain, is an inhibitor of microtubule growth and shortening that interacts with EBs on the microtubule surface and with a luminal microtubule-pausing factor CSPP1. Another TOG-domain protein, TOGARAM1, overcomes growth inhibition imposed by CEP104 and CSPP1. CCDC66 and ARMC9 do not affect microtubule dynamics directly but act as scaffolds for their partners. Cryo-electron tomography showed that together, ciliary tip module members form plus-end-specific cork-like structures which reduce protofilament flaring. The combined effect of these proteins is very slow processive microtubule elongation, which recapitulates axonemal dynamics in cells.
Core-N-glycans are atypically abundant at the neuronal surface and regulate glutamate receptor signaling
Authors: Zhang Chun-Lei , Moutoussamy Cédric , Tuffery Matthieu , Varangot Alexandre , Piskorowski Rebecca , Hanus Cyril 
Published: March 2024

AbstractNeurotransmitter receptors, like most surface proteins, are extensively modified by covalent addition of N-glycans during their synthesis. Surprisingly, the most abundant N-glycans in the mammalian brain are core-glycans, sugars that typically earmark immature intracellular proteins in non-neuronal cells. The function of these glycans in neurons is yet largely unknown. To address this, we combined conditional gene knockout, mass spectrometry, quantitative imaging and electrophysiological recordings in cultured neurons and brain slices. We show that core-glycans are expressed at high levels at the neuronal surface, indicating expression on functional proteins. Focusing on excitatory synapses, we found that core-glycans reduce dendritic spine density and synaptic AMPA receptor expression but are overall sufficient to sustain functional synapses. Our results indicate that core-glycans slow the desensitization of AMPA receptor complexes and reduce NMDA receptor signaling at synapses. Core-glycans hence impair NMDA receptor-dependent synaptic plasticity, unraveling a previously unrecognized role for N-glycosylation in regulating synaptic composition and transmission efficacy.