bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunopharmacological evaluation of adjuvant efficacy of Monophosphoryl lipid-A and CpG ODN with SARS-CoV-2 RBD antigen
Authors: Sambyal Shainy , Sravanthi Vemireddy , Khatri Ritika , Siddqui Gazala , Ahmed Shubbir , Samal Sweety , Sampath Kumar Halmuthur M 
Published: April 2022

AbstractSARS-CoV-2 infection has made the mankind to witness most sever and serious pandemic situation in the history. Millions of people have suffered and are still suffering with this infection which has caused a mass mortality in the past three years. Development of an effective vaccine to control the spread of infection and to prevent this viral infection is need of the hour. Adjuvanted vaccines have proven their efficacy in controlling many other viral infections like flu, keeping this context in view we have evaluated the immunopharmacological efficacy of two adjuvants MPL-A and CpG ODN in combination with MF59 emulsion against SARS-CoV-2 antigen. From the data obtained we can infer that both the adjuvants were capable of eliciting a potent antibody response against antigen alone and MF59 groups. Comparatively MPL-A was eliciting a Th1 polarized response in terms of IgG2a and cytokine production. Both the adjuvants were capable of enhancing the CD 4, 8 and 19 cell populations. Overall the pre clinical evaluation has given a clue of the effectiveness of MPL-A and CpG adjuvants against SARS-CoV-2 antigen.
The strength of feedback processing is associated with resistance to visual backward masking during illusory contour processing in adult humans
Authors: Foxe John J. , Knight Emily J. , Myers Evan J. , Cao Cody Zhewei , Molholm Sophie , Freedman Edward G. 
Published: April 2022

ABSTRACTRe-entrant feedback processing is a key mechanism of visual object-recognition, especially under compromised viewing conditions where only sparse information is available and object features must be interpolated. Illusory contour stimuli are commonly used in conjunction with visual evoked potentials (VEP) to study these filling-in processes, with characteristic modulation of the VEP in the ~100-150ms timeframe associated with this re-entrant processing. Substantial inter-individual variability in timing and amplitude of feedback-related VEP modulation is observed, raising the question whether this variability might underlie inter-individual differences in the ability to form strong perceptual gestalts. Backward masking paradigms have been used to study inter-individual variance in the ability to form robust object perceptions before processing of the mask interferes with object-recognition. Some individuals recognize objects when the time between target object and mask is extremely short, whereas others struggle to do so even at longer target-to-mask intervals. We asked whether timing and amplitude of feedback-related VEP modulations were associated with individual differences in resistance to backward masking. Participants (N=40) showed substantial performance variability in detecting illusory contours at intermediate target-to-mask intervals (67ms and 117ms), allowing us to use kmeans clustering to divide the population into four performance groups (poor, low-average, high-average, superior). There was a clear relationship between the amplitude (but not the timing) of feedback-related VEP modulation and illusory contour detection during backward masking. We conclude that individual differences in the strength of feedback processing in neurotypical humans lead to differences in the ability to quickly establish perceptual awareness of incomplete visual objects.
CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever
Authors: Shu Bo , Ooi Justin S.G. , Tan Aaron W.K , Ng Thiam-Seng , Dejnirattisai Wanwisa , Mongkolsapaya Juthathip , Fibriansah Guntur , Shi Jian , Kostyuchenko Victor A. , Screaton Gavin , Lok Shee-Mei 
Published: April 2022

AbstractDengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional: the intracellular dimeric NS1 (iNS1) forms part of the viral replication complex, the extracellular multi-oligomeric secreted NS1 (sNS1) is a major factor contributing to DHF. The structure of the iNS1 is well studied but not sNS1. Here we show the tetrameric (stable and loose conformation) and hexameric structures of sNS1. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain – elongated β-sheet or β-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.
Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders
Authors: Invernizzi Azzurra , Rechtman Elza , Curtin Paul , Papazaharias Demetrios M. , Jalees Maryam , Pellecchia Alison C. , Bromet Evelyn J. , Lucchini Roberto G. , Luft Benjamin J. , Clouston Sean A. , Tang Cheuk Y. , Horton Megan K. 
Published: April 2022

AbstractWorld Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have higher prevalence (23%) of persistent, clinically significant WTC-related post-traumatic stress disorder (WTC-PTSD). Here, we applied eigenvector centrality (EC) metrics and data driven methods on resting state functional magnetic resonance (fMRI) outcomes to investigate neural mechanisms underlying WTC-PTSD and to identify how EC shifts in brain areas relate to WTC-exposure and behavioral symptoms. Nine brain areas differed significantly and contributed the most to differentiate functional neuro-profiles between WTC-PTSD and non-PTSD responders. The association between WTC-exposure and EC values differed significantly between WTC-PTSD and non-PTSD in the right anterior parahippocampal gyrus and left amygdala (p= 0.010; p= 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, the index of PTSD symptoms was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Our understanding of functional changes in neural mechanisms underlying WTC-related PTSD is key to advance intervention and treatment.
Zebrafish Galectin 3 binding protein (Lgals3bp) is the target antigen of the microglial 4C4 monoclonal antibody
Authors: Rovira Mireia , Montanari Alice , Hammou Latifa , Chomette Laura , Miserocchi Magali , Pozo Jennifer , Imbault Virginie , Bisteau Xavier , Wittamer Valérie 
Published: April 2022

ABSTRACTBackgroundTwo decades ago, the fish-specific monoclonal antibody 4C4 was found to be highly reactive to zebrafish microglia, the macrophages of the central nervous system. This has resulted in 4C4 being widely used, in combination with available fluorescent transgenic reporters to identify and isolate microglia. However, the target protein of 4C4 remains unidentified, which represents a major caveat. In addition, whether the 4C4 expression pattern is strictly restricted to microglial cells in zebrafish has never been investigated.ResultsHaving demonstrated that 4C4 is able to capture its native antigen from adult brain lysates, we used immunoprecipitation/mass-spectrometry, coupled to recombinant expression analyses, to identify its target. The cognate antigen was found to be a paralog of Galectin 3 binding protein (Lgals3bpb), known as MAC2-binding protein in mammals. Notably, 4C4 did not recognize other paralogs, demonstrating specificity. Moreover, our data show that Lgals3bpb expression, while ubiquitous in microglia, also identifies leukocytes in the periphery, including populations of gut and liver macrophages.ConclusionsThe 4C4 monoclonal antibody recognizes Lgals3bpb, a predicted highly glycosylated protein whose function in the microglial lineage is currently unknown. Identification of Lgals3bpb as a new pan-microglia marker will be fundamental in forthcoming studies using the zebrafish model.
Developmental switch in prediction and adaptation to pain in human neonates
Authors: Rupawala Mohammed , Bucsea Oana , Laudiano-Dray Maria Pureza , Whitehead Kimberley , Meek Judith , Fitzgerald Maria , Olhede Sofia , Jones Laura , Fabrizi Lorenzo 
Published: April 2022

ABSTRACTHabituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain and indicates the ability of the brain to encode expectation of imminent nociception. However, it is not known whether the newborn brain can predict and habituate to recurrent noxious inputs. We used electroencephalography to investigate changes in cortical microstates, which represent the complex sequential processing of noxious inputs, following repeated clinically-required heel lances in term and preterm infants. Noxious stimulus repetition decreased the engagement of early sensory-related microstates and associated behavioural and physiological responses in term infants, while preterm infants did not show signs of adaptation. Nevertheless, both groups displayed a switch between different microstates at longer latencies. These data suggests that the preterm brain is capable of encoding high-level contextual differences in pain, but cannot update its prediction, which allows for adaptation, emphasising the vulnerability of this population to recurrent pain.
Targeted protein S-nitrosylation of ACE2 as potential treatment to prevent spread of SARS-CoV-2 infection
Authors: Oh Chang-ki , Nakamura Tomohiro , Beutler Nathan , Zhang Xu , Piña-Crespo Juan , Talantova Maria , Ghatak Swagata , Trudler Dorit , Carnevale Lauren N. , McKercher Scott R. , Bakowski Malina A. , Diedrich Jolene K. , Roberts Amanda J. , Woods Ashley K. , Chi Victor , Gupta Anil K. , Rosenfeld Mia A. , Kearns Fiona L. , Casalino Lorenzo , Shaabani Namir , Liu Hejun , Wilson Ian A. , Amaro Rommie E. , Burton Dennis R. , Yates John R. , Becker Cyrus , Rogers Thomas F. , Chatterjee Arnab K. , Lipton Stuart A. 
Published: April 2022

AbstractPrevention of infection and propagation of SARS-CoV-2 is of high priority in the COVID-19 pandemic. Here, we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 Spike protein, thereby inhibiting viral entry, infectivity, and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and thus spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E-protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model, and thus provide a novel avenue for therapy.
HOTARU: Automatic sorting system for large-scale calcium imaging data
Authors: Takekawa Takashi , Nomoto Masanori , Asai Hirotaka , Ohkawa Noriaki , Okubo-Suzuki Reiko , Ghandour Khaled , Sato Masaaki , Ohkura Masamichi , Nakai Junichi , Muramatsu Shin-ichi , Hayashi Yasunori , Inokuchi Kaoru , Fukai Tomoki 
Published: April 2022

AbstractCurrently, calcium imaging allows long-term recording of large-scale neuronal activity in diverse states. However, it remains difficult to extract neuronal dynamics from recorded imaging data. In this study, we propose an improved constrained nonnegative matrix factorization (CNMF)-based algorithm and an effective method to extract cell shapes with fewer false positives and false negatives through image processing. We also show that the evaluation metrics obtained during image and signal processing can be combined and used for false-positive cell determination. For the CNMF algorithm, we combined cell-by-cell regularization and baseline shrinkage estimation, which greatly improved its stability and robustness. We applied these methods to real data and confirmed their effectiveness. Our method is simpler and faster, detects more cells with lower firing rates and signal-to-noise ratios, and enhances the quality of the extracted cell signals. These advances can improve the standard of downstream analysis and contribute to progress in neuroscience.
Mind the gap: Nodes of Ranvier are remodeled by chronic psychosocial stress and neuronal activity
Authors: Koskinen M-K , Laine MA , Abdollahzadeh A , Gigliotta A , Mazzini G , Journée SH , Alenius V , Trontti K , Tohka J , Hyytiä P , Sierra A , Hovatta I 
Published: April 2022

AbstractDifferential expression of myelin-related genes and changes in myelin thickness have been demonstrated in mice after chronic psychosocial stress, a risk factor for anxiety disorders. To determine whether and how stress affects structural remodeling of nodes of Ranvier, another form of myelin plasticity, we developed a 3D reconstruction analysis of node morphology in C57BL/6NCrl and DBA/2NCrl mice. We identified strain-dependent effects of chronic stress on node morphology, including elongation of paranodes in the medial prefrontal cortex (mPFC) in DBA/2NCrl mice. Furthermore, chronic chemogenetic activation of the ventral hippocampus-to-mPFC pathway resulted in increased risk assessment behavior and shortened paranodes specifically in stimulated axons, providing a direct link between anxiety-like behavior and remodeling of the nodes. Altogether, our data demonstrate genetic regulation of nodal remodeling in stress and suggest an activity-dependent regulation of paranodes in anxiety-related circuits. Nodal remodeling may thus contribute to the aberrant circuit function associated with anxiety disorders.
Comparative study between radiofrequency-induced and muscimol-induced inhibition of cultured networks of cortical neuron
Authors: Lemercier Clément E. , Garenne André , de Gannes Florence Poulletier , El Khoueiry Corinne , Arnaud-Cormos Delia , Levêque Philippe , Lagroye Isabelle , Percher-ancier Yann , Lewis Noёlle 
Published: April 2022

AbstractPrevious studies have shown that spontaneously active cultured networks of cortical neuron grown planar microelectrode arrays are sensitive to radiofrequency (RF) fields and exhibit an inhibitory response more pronounced as the exposure time and power increase. To better understand the mechanism behind the observed effects, we aimed at identifying similarities and differences between the inhibitory effect of RF fields (continuous wave, 1800 MHz) to the γ-aminobutyric acid type A (GABAA) receptor agonist muscimol (MU). Inhibition of the network bursting activity in response to RF exposure became apparent at an SAR level of 28.6 W/kg and co-occurred with an elevation of the culture medium temperature of ~1 °C. Exposure to RF fields preferentially inhibits bursting over spiking activity and exerts fewer constraints on neural network bursting synchrony, differentiating it from a pharmacological inhibition with MU. Network rebound excitation, a phenomenon relying on the intrinsic properties of cortical neurons, was observed following the removal of tonic hyperpolarization after washout of MU but not in response to cessation of RF exposure. This implies that hyperpolarization is not the main driving force mediating the inhibitory effects of RF fields. At the level of single neurons, network inhibition induced by MU and RF fields occurred with reduced action potential (AP) half-width. As changes in AP waveform strongly influence efficacy of synaptic transmission, the narrowing effect on AP seen under RF exposure might contribute to reducing network bursting activity. By pointing only to a partial overlap between the inhibitory hallmarks of these two forms of inhibition, our data suggest that the inhibitory mechanisms of the action of RF fields differ from the ones mediated by the activation of GABAA receptors.
Asynchrony rescues statistically-optimal group decisions from information cascades through emergent leaders
Authors: Reina Andreagiovanni , Bose Thomas , Srivastava Vaibhav , Marshall James A. R. 
Published: April 2022

AbstractIt is usually assumed that information cascades are most likely to occur when an early but incorrect opinion spreads through the group. Here we analyse models of confidence-sharing in groups and reveal the opposite result: simple but plausible models of naïve Bayesian decision-making exhibit information cascades when group decisions are synchronous; however, when group decisions are asynchronous, the early decisions reached by Bayesian decision makers tend to be correct, and dominate the group consensus dynamics. Thus early decisions actually rescue the group from making errors, rather than contribute to it. We explore the likely realism of our assumed decision-making rule with reference to the evolution of mechanisms for aggregating social information, and known psychological and neuroscientific mechanisms.
Hyperglycemia and Cancer. Human lung carcinoma by means of Raman spectroscopy and imaging
Authors: Abramczyk H. , Kopeć M. , Beton K. 
Published: April 2022

AbstractRaman spectroscopy and Raman imaging allow to identify the biochemical and structural features of human cancer lung cell line (CCL-185) and the cell line supplemented with glucose and deuterated glucose in normal and hyperglycemia conditions. We found that isotope substitution of glucose by deuterated glucose allows to separate de novo lipid synthesis from exogenous uptake of lipids obtained from the diet. We demonstrated that glucose is largely utilized for de novo lipid synthesis. Our results provide a direct evidence that high level of glucose decreases the metabolism via oxidative phosporylation in mitochondria in cancer cells and shifts the metabolism to glycolysis via Wartburg effect.Graphical Abstract
MicroRNA inhibition using antimiRs in acute human brain tissue sections
Authors: Morris Gareth , Langa Elena , Fearon Conor , Conboy Karen , E-How Kelvin Lau , Sanz-Rodriguez Amaya , O’Brien Donncha F , Sweeney Kieron , Lacey Austin , Delanty Norman , Beausang Alan , Brett Francesca M , Cryan Jane B , Cunningham Mark O , Henshall David C 
Published: April 2022

AbstractIntroductionAn emerging pre-clinical approach for the treatment of pharmacoresistant epilepsy is targeting the microRNA (miRNA) system. MiRNAs are short noncoding RNAs that suppress gene expression at the post-transcriptional level. Targeting miRNAs, which is possible using antisense oligonucleotide ‘antimiRs’ can produce broad effects on gene expression suited to the complex pathophysiology in temporal lobe epilepsy. Potent anti-seizure and disease- modifying effects have been reported for antimiRs targeting microRNA-134 (antimiR-134). To date, however, pre-clinical testing has been performed using in vitro cell cultures and rodent models. It is uncertain how well this approach will translate to the clinic. Here, we develop an antimiR testing platform in human brain tissue sections.MethodologyHuman brain specimens were obtained with consent from patients undergoing resective surgery to treat focal drug-resistant epilepsy. Neocortical specimens were submerged in modified artificial cerebrospinal fluid (ACSF), dissected for clinical neuropathological examination, and unused material transferred for sectioning. Individual tissue sections were incubated in oxygenated ACSF, containing either antimiR-134 or a non-targeting control antimiR, for 24 hours at room temperature. RNA integrity was assessed using BioAnalyzer processing, and individual miRNA levels measured using RT-qPCR.ResultsACSF transport had no obvious impact on any clinical neurosurgical or neuropathological procedure and specimens were confirmed to be viable following this process. RNA was well- preserved by transportation of specimens in ACSF, with RNA integrity scores significantly higher than tissue transported without ACSF. AntimiR-134 mediated a specific and dose- dependent knockdown of miR-134 in human neocortical sections, with approximately 75% reduction of miR-134 at 1 µM and 90% reduction at 3 µM. These doses did not have off- target effects on expression of a selection of three other miRNAs (miR-10, miR-129 or miR- 132).SignificanceThis is the first demonstration of antimiR-134 effects in live human brain tissues. The findings lend further support to the preclinical development of miR-134 and offer a flexible platform for the pre-clinical testing of antimiRs, and other antisense oligonucleotide therapeutics, in human brain.Key pointsASO antimiRs are promising treatments for pharmacoresistant epilepsyWe developed a pipeline to preserve live human neocortical brain specimens from people undergoing resective surgeryRNA integrity was sufficient to measure miRNA levels in human brain tissues transported in modified ACSFIncubation of acute human neocortical specimens in antimiR-134 resulted in potent and specific reduction in miR-134 levelsAcute human brain slices are a promising model for testing ASOs
Concentration dependent dual effect of the endozepine ODN on neuronal spiking activity
Authors: Hazime M , Gasselin M , Alasoadura M , Lanfray D , Leclerc J , Lefranc B , Basile M , Duparc C , Vaudry D , Leprince J , Chuquet J 
Published: April 2022

AbstractEndozepines, known as the endogenous ligands of benzodiazepine-binding sites, include the diazepam binding inhibitor (DBI) and its processing products, the triakontatetraneuropeptide (TTN) and the octadecaneuropeptide (ODN). Despite indisputable evidences of the binding of ODN on GABAAR-BZ-binding sites, their action on this receptor lacks compelling electrophysiological observations, some studies reporting that ODN acts as a negative allosteric modulator (NAM) of GABAAR while others suggest the opposite (positive allosteric modulation, PAM effect). All these studies were carried out in vitro with various neuronal cell types. To further elucidate the role of ODN on neuronal excitability, we tested its effect in vivo in the cortex of the anesthetized mouse. Spontaneous neuronal spikes were recorded by the mean of an extracellular pipette in the vicinity of which ODN was micro-infused, either at high dose (10-5M) or low dose (10-11M). ODN at high dose induced a significant increase of neuronal spiking. This effect could be antagonized by the GABAAR-BZ-binding sites blocker flumazenil. In sharp contrast, at low concentration, ODN reduced neuronal spiking in a magnitude similar to GABA itself. Interestingly, this decrease of neuronal activity by low dose of ODN was not flumazenil dependent suggesting that this effect is mediated by another receptor. Finally, we show that astrocytes in culture, known to be stimulated by picomolar dose of ODN via a GPCR, increased their export of GABA when stimulated by low dose of ODN. Our results confirm the versatility of ODN in the control of GABA transmission, but suggest that its PAM-like effect is, at least in part, mediated via an astrocytic non-GABAAR ODN receptor.