bluuebunny/crossref_metadata_2025_split huggingface dataset:
A peptide-neurotensin conjugate that crosses the blood-brain barrier induces pharmacological hypothermia associated with anticonvulsant, neuroprotective and anti-inflammatory properties following status epilepticus in mice
Authors: Ferhat Lotfi , Soussi Rabia , Masse Maxime , Kyriatzis Grigorios , Girard Stéphane D. , Gassiot Fanny , Gaudin Nicolas , Laurencin Mathieu , Bernard Anne , Bôle Angélique , Ferracci Géraldine , Smirnova Maria , Roman François , Dive Vincent , Cisternino Salvatore , Temsamani Jamal , David Marion , Lécorché Pascaline , Jacquot Guillaume , Khrestchatisky Michel 
Published: July 2024

ABSTRACTPreclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to be efficient in pharmacologically induced hypothermia (PIH). Neurotensin (NT), a 13 amino-acid neuropeptide that regulates body temperature, interacts with various receptors to mediate its peripheral and central effects. NT induces PIH when administered intracerebrally. However, these effects are not observed if NT is administered peripherally, due to its rapid degradation and poor passage of the blood brain barrier (BBB). We conjugated NT to peptides that bind the low-density lipoprotein receptor (LDLR) to generate “vectorized” forms of NT with enhanced BBB permeability. We evaluated their effects in epileptic conditions following peripheral administration. One of these conjugates, VH-N412, displayed improved stability, binding potential to both the LDLR and NTSR-1, rodent/human cross-reactivity and improved brain distribution. In a mouse model of kainate (KA)-induced status epilepticus (SE), VH-N412 elicited rapid hypothermia associated with anticonvulsant effects, potent neuroprotection and reduced hippocampal inflammation. VH-N412 also reduced sprouting of the dentate gyrus mossy fibers and preserved learning and memory skills in the treated mice. In cultured hippocampal neurons, VH-N412 displayed temperature-independent neuroprotective properties. To the best of our knowledge, this is the first report describing the successful treatment of SE with PIH. In all, our results show that vectorized NT may elicit different neuroprotection mechanisms mediated either by hypothermia and/or by intrinsic neuroprotective properties.
Criticality explains structure-function relationships in the human brain
Authors: Angiolelli Marianna , Scarpetta Silvia , Sorrentino Pierpaolo , Lopez Emahnuel Troisi , Quarantelli Mario , Granata Carmine , Sorrentino Giuseppe , Palmieri Vincenzo , Messuti Giovanni , Stefano Mattia , Filippi Simonetta , Cherubini Christian , Loppini Alessandro , Chiodo Letizia 
Published: July 2024

AbstractHealthy brain exhibits a rich dynamical repertoire, with flexible spatiotemporal patterns replays on both microscopic and macroscopic scales. How do fixed structural connections yield a diverse range of dynamic patterns in spontaneous brain activity? We hypothesize that the observed relationship between empirical structure and functional patterns is best explained when the microscopic neuronal dynamics is close to a critical regime. Using a modular Spiking Neuronal Network model based on empirical connectomes, we posit that multiple stored functional patterns can transiently reoccur when the system operates near a critical regime, generating realistic brain dynamics and structural-functional relationships. The connections in the model are chosen as to force the network to learn and propagate suited modular spatiotemporal patterns. To test our hypothesis, we employ magnetoencephalography and tractography data from five healthy individuals. We show that the critical regime of the model is able to generate realistic features, and demonstrate the relevance of near-critical regimes for physiological brain activity.
Neophobic response of bull ants (Myrmecia midas) to odours introduced on their foraging route
Authors: Kambala Venkata Manvitha , Ahmed Yousef , Lee Jasmine , Jose Anwin , Nadir Sahera Syed , Priyanka B C , Gabir Ali , Sun Yingdie , Cheng Ken , Deeti Sudhakar 
Published: July 2024

ABSTRACTGoal-oriented learning and navigation is well known in eusocial insects. The solitary foraging of nocturnal bull antsMyrmecia midasin their visually complex environment relies on path integration and landmark learning. While this species seems to be ‘sensitive’ to handling and reacts to visual changes in their surroundings, not much is known about how added olfactory stimuli impact their route navigation on a vertical surface. In the current study, we added one of five different invisible odours on the trees on which foragers normally forage. We found that the bull ants showed neophobic responses to all the odours. The Tea-tree and Lavender odours showed the strongest impact on the bull ants’ navigation by causing detours, U-turns, and avoidance of the sensory stimuli, with the ants meandering more and scanning more frequently. The odours of Olive oil, Flax-seed oil, and Eucalyptus oil had a moderate impact on the ants’ navigation. These findings showed the widespread influence of non-visual chemical cues in shaping bull ant navigation and highlight the induction of neophobic responses stemming from chemical alterations on learned routes. Overall, this study contributes to the understanding of the effects of foreign odours, adding to our understanding of the complex learning processes of bull ants in their vertical navigation.
On the synergy between myelin proteins P0, MBP, and P2 in peripheral nerve major dense line formation
Authors: Krokengen Oda C. , Raasakka Arne , Klenow Martin Berg , Pal Antara , Hetland Øystein , Mularski Anna , Ruskamo Salla , Pedersen Jan Skov , Simonsen Adam Cohen , Kursula Petri 
Published: July 2024

AbstractMyelin is a proteolipid membrane multilayer held together by a set of proteins. The proper formation and function of the myelin sheath relies on the coordinated action of several key myelin proteins. Research exploring how proteins from the peripheral myelin cytoplasmic apposition – myelin basic protein (MBP), the cytoplasmic tail of myelin protein zero (P0ct), and peripheral myelin protein 2 (P2) – interact with each other and with myelin-like membranes was conducted using various techniques, such as small-angle X-ray diffraction (SAXD), differential scanning calorimetry (DSC), surface plasmon resonance (SPR), as well as electron and live epifluorescence microscopy. DSC revealed changes in lipid interactions depending on the protein combination, with MBP and P0ct binding more tightly to lipid membranes than P2, resulting in altered membrane fluidity and stability. These results were supported by SPR, which indicated that the myelin proteins may compete for membrane surface binding. Analysis of the Bragg peaks induced by the myelin proteins in lipidic environments showed both lamellar and non-lamellar phases in protein-lipid complexes. The results indicate both synergy and competition between the three main proteins residing in the PNS myelin major dense line. Furthermore, the observed direct effects of myelin proteins on lipid membrane properties may be relevant to their function in myelinating cells.
BMAP: a comprehensive and reproducible biomedical data analysis platform
Authors: Ren Yongyong , Cheng Zhiwei , Li Leijie , Zhang Yuening , Dai Fang , Deng Luojia , Wu Yijie , Gu Jianlei , Lin Qingmin , Wang Xiaolei , Kong Yan , Lu Hui 
Published: July 2024

AbstractIn the realm of biomedical research, efficient data analysis and processing are crucial due to the escalating volume and complexity of data generated by research teams. Managing these vast arrays of localized data presents significant challenges, necessitating precise, efficient, and reproducible analysis methodologies to ensure the integrity and reliability of scientific outcomes. Traditional management of analysis codes, computing environments, and the inherent difficulties in result traceability due to team dynamics often lead to inefficiencies and potential risks in maintaining academic integrity. Furthermore, while online storage platforms such as Dryad, GitHub, and Docker facilitate data, code, and environment management, they do not inherently guarantee the reproducibility of results, with issues like data incompleteness, forgotten parameters, or software discrepancies posing additional challenges. To address these critical gaps, we developed a BioMedical data Analysis Platform (BMAP) to offer online and localized categorized management of research assets. BMAP enhances workflow efficiency by transforming complex pipelines into user-friendly web applications, promoting consistency and standardization across team analyses. Its comprehensive web analysis module and seamless integration with data and computing resources support automated result reproducibility and visualization. According to the assessment, 1,692 omics-related figures from 101 recent articles, across 45 visualization types, were tested with BMAP, which could cover 37.8% of the types and 64.3% of the figures. BMAP also enables the sharing and enhancement of research methods through its cloud platform, allowing researchers to utilize the previously developed and validated tools, thereby reducing redundant effort and minimizing analytical discrepancies due to methodological differences.
Comprehensive elucidation of glutathione import inEscherichia coli
Authors: Knoke Lisa R. , Muskietorz Maik , Kühn Lena , Leichert Lars I. 
Published: July 2024

AbstractGlutathione is the major thiol-based antioxidant in a wide variety of biological systems, ranging from bacteria to eukaryotes. As a redox couple, consisting of reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), it is crucial for the maintenance of the cellular redox balance. Glutathione transport out of and into cellular compartments and the extracellular space is a determinant of the thiol-disulfide redox state of the organelles and bodily fluids in question, but is currently not well understood. Here we use the genetically-encoded, glutathione-measuring redox probe Grx1-roGFP2 to comprehensively elucidate the import of extracellular glutathione into the cytoplasm of the model organismEscherichia coli. The elimination of only two ATP-Binding Cassette (ABC) transporter systems, Gsi and Opp, completely abrogates glutathione import intoE. coli’s cytoplasm, both in its reduced and oxidized form. The lack of only one of them, Gsi, completely prevents import of oxidized glutathione (GSSG), while the lack of the other, Opp, substantially retards the uptake of reduced glutathione (GSH).
Congruent timing in Human, Nightingale, Parotid Wasp and Hawaiian Planthopper vocalisations
Authors: Fourcin Adrian 
Published: July 2024

AbstractEarlier multi-speaker, multi-language measurements found that in purposeful fluent speech, total voice duration was half that of the whole – a maximum Shannon entropy criterion for two state signals. The present aim is to discover whether other species’ vocalisations are similarly associated with maximum timing entropy control. Data selection has been based on the use of courtship songs since they are purposeful and fluent. These songs are intended for con-specific females and, at present, often too complex for reliable acoustic signal analysis. In consequence it has been necessary, for this preliminary study, to find courtship songs in which the echemes are well demarcated from silence – this has led to a curtailment of potential signal resources.The vocalisation timings in examples of the courtship songs of Nightingale, Parotid Wasp and Hawaiian Planthopper have been analysed. The resulting measurements are compared with those for voice timing in purposeful fluent, human speech. There are three primary findings:The same Shannon timing entropy maximising rule is intrinsic to all four vocalisations.Gaussian distributions of voice/vocalisation timings are present for each of the four signal types.In each case, maximum entropy of voice/vocalisation timing tends to be maintained continually throughout the production of the whole signal.
HINT1 Inhibitors as Selective Modulators of MOR-NMDAR Cross Regulation and Non-Opioid Analgesia
Authors: Dillenburg Maxwell , Peterson Cristina D. , Dolat Rafal , Ligori Kostana , Kitto Kelley F , Wilcox George L , Fairbanks Carolyn A. , Wagner Carston R. 
Published: July 2024

AbstractThe Human Histidine Triad Nucleotide Binding Protein 1 (HINT1) has recently become a protein of interest due to its involvement in several CNS processes, including neuroplasticity and the development of several neuropsychiatric disorders. Crucially, HINT1 behaves as a mediator for the cross-regulation of the mu opioid receptor (MOR) andN-methyl-D-aspartate receptor (NMDAR). Active site inhibition of HINT1 using small molecule inhibitors has been demonstrated to have a significant impact on this cross-regulatory relationshipin vivo. Herein, we describe the development of a series of ethenoadenosine HINT1 inhibitors to further evaluate the effect of HINT1 inhibition on morphine’s blockade of NMDA-evoked behaviors, the development of acute endomorphin-2 tolerance and analgesia. X-ray crystallographic analysis and HINT1 binding experiments demonstrate that modifications to the inhibitor nucleobase greatly impact the inhibitor binding interactions with HINT1. Our results reveal a complex structural-activity relationship for HINT1 inhibitors in which minor modifications to the ethenoadenosine scaffold resulted in dramatic changes to their activity in these assays modeling MOR-NMDAR interaction. Specifically, we observed the ability of HINT1 inhibitors to selectively affect individual pathways of MOR-NMDAR crosstalk. Furthermore, we observed that a carbamate ethenoadenosine inhibitor of HINT1 can induce analgesia, while not affecting opioid tolerance. Additionally, although past studies have indicated that that loss of HINT1 expression can result in the downregulation of p53, we have shown that inhibition of HINT1 has no effect on either the expression of HINT1 or p53. These studies highlight the critical role of HINT1 in MOR-NMDAR crosstalk and demonstrate the intriguing potential of using HINT1 active-site inhibitors as tools to probe its role in these biochemical pathways and its potential as a novel pain target.
Antigen-Specific modulation of Chronic Experimental Autoimmune Encephalomyelitis in Humanized Mice by TCR-like Antibody Targeting Auto-Reactive T-Cell Epitope
Authors: Goor Ilana , Altman Efrat , Arman Inbar , Haus-Cohen Maya , Reiter Yoram 
Published: July 2024

AbstractThe development and application of human T-cell receptor (TCR)-like antibodies (TCRL) recognizing disease-specific peptide-MHC complexes may prove an important tool for basic research and therapeutic applications.Multiple Sclerosis is characterized by aberrant CD4 T cell response to self-antigens presented by class II MHC molecules. This led us to select a panel of TCRL Abs targeting the immunodominant autoantigenic epitope MOG35-55 derived from Myelin Oligodendrocyte Glycoprotein (MOG) presented on HLA-DR2 which is associated with Multiple Sclerosis (MS).We demonstrate that these TCRL Abs bind with high specificity to human HLA-DR2/ MOG35-55 derived MHC class II molecules and can detect APCs that naturally present the MS-associated autoantigen in humanized EAE transgenic mouse model. The TCRLs can block ex vivo and in vivo CD4 T-cell proliferation in response to MOG35-55 stimulation in an antigen-specific manner. Most significant, administration of TCRL to MOG35-55 induced EAE model in HLA-DR2 transgenic mice both prevents and regresses established EAE. TCRL function was associated with reduction of autoreactive pathogenic T cells infiltration into the CNS, along with modulation of activated CD11b+ macrophages/microglia APCs.Collectively, these findings demonstrate the combined action of TCRL Abs in blocking TCR-MHC interactions and modulating APC presentation and activation, leading to a profound antigen-specific inhibitory effect on the neuroinflammatory process, resulting in regression of EAE.Our study constitutes an in vivo proof-of-concept for the utility of TCR-like antibodies as antigen-specific immunomodulators for CD4-mediated autoimmune diseases such as multiple sclerosis (MS), validating the importance of the TCR-MHC axis as a therapeutic target for various autoimmune and inflammatory diseases.
Proxi-RIMS-seq2 applied to native microbiomes uncovers hundreds of known and novelm5C methyltransferase specificities
Authors: Yang Weiwei , Luyten Yvette , Reister Emily , Mangelson Hayley , Sisson Zach , Auch Benjamin , Liachko Ivan , Roberts Richard J. , Ettwiller Laurence 
Published: July 2024

AbstractMethylation patterns in bacteria can be used to study Restriction-Modification (RM) or other defense systems with novel properties. Whilem4C andm6A methylation is well characterized mainly through PacBio sequencing, the landscape ofm5C methylation is under-characterized. To bridge this gap, we performed RIMS-seq2 on microbiomes composed of resolved assemblies of distinct genomes through proximity ligation. This high-throughput approach enables the identification ofm5C methylated motifs and links them to cognate methyltransferases directly on native microbiomes without the need to isolate bacterial strains. Methylation patterns can also be identified on viral DNA and compared to host DNA, strengthening evidence for virus-host interaction. Applied to three different microbiomes, the method unveils over 1900 motifs that were deposited in REBASE. The motifs include a novel 8-base recognition site (CATm5CGATG) that was experimentally validated by characterizing its cognate methyltransferase. Our findings suggest that microbiomes harbor arrays of untappedm5C methyltransferase specificities, providing insights to bacterial biology and biotechnological applications.
Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus
Authors: Daume Jonathan , Kamiński Jan , Salimpour Yousef , Anderson William S. , Valiante Taufik A. , Mamelak Adam N. , Rutishauser Ueli 
Published: July 2024

AbstractWorking Memory (WM) and Long-Term Memory (LTM) are often viewed as separate cognitive systems. Little is known about how these systems interact when forming memories. We recorded single neurons in the human medial temporal lobe while patients maintained novel items in WM and a subsequent recognition memory test for the same items. In the hippocampus but not the amygdala, the level of WM content-selective persist activity during WM maintenance was predictive of whether the item was later recognized with high confidence or forgotten. In contrast, visually evoked activity in the same cells was not predictive of LTM formation. During LTM retrieval, memory-selective neurons responded more strongly to familiar stimuli for which persistent activity was high while they were maintained in WM. Our study suggests that hippocampal persistent activity of the same cell supports both WM maintenance and LTM encoding, thereby revealing a common single-neuron component of these two memory systems.
An essential role for the Hv1 voltage-gated proton channel inPseudomonas aeruginosacorneal infection
Authors: Rodriguez Priscila , Abbondante Serena , Marshall Michaela , Abdelmeseh Jessica , Tombola Francesco , Pearlman Eric 
Published: July 2024

ABSTRACTAssembly of NADPH oxidase 2 (NOX2) proteins in neutrophils plays an essential role in controlling microbial infections by producing high levels of reactive oxygen species (ROS). In contrast, the role of the Hv1 voltage-gated proton channel that is required for sustained NOX2 activity is less well characterized. We examined the role of Hv1 in a murine model of blindingPseudomonas aeruginosacorneal infection and found that in contrast to C57BL/6 mice,Hvcn1-/-mice exhibit an impaired ability to kill bacteria and regulate disease severity.In vitro, we used a novel Hv1 Inhibitor Flexible (HIF) to block ROS production by human and murine neutrophils and found that HIF inhibits ROS production in a dose-dependent manner following stimulation with PMA or infection withP. aeruginosa. Collectively, these findings demonstrate an important role for Hv1 on controlling bacterial growth in a clinically relevant bacterial infection model.
Identifying candidate items for a prototype index on propensity to integrate research evidence into clinical decision-making in rehabilitation
Authors: Roberge-Dao Jacqueline , Thomas Aliki , Rochette Annie , Shikako Keiko , Mayo Nancy 
Published: July 2024

AbstractPurposeExisting measures of evidence-based practice (EBP) in rehabilitation provide a fragmented interpretation of EBP competencies as performance is rated on discrete domains without a harmonized measure to represent the multidimensionality of EBP. Building on previous work, this study aimed to provide evidence that a brief multidimensional index can be formed to determine a clinician’s propensity to integrate research evidence into decision-making to inform the subsequent development process.MethodsUsing a Canadian dataset of occupational and physical therapists (n=127) who responded to a survey containing 70 frequently used items to measure EBP (representing six domains), one item per key EBP domain was selected using Rasch measurement theory and expert consensus. A preliminary scoring algorithm was developed for testing purposes. The interpretability of the prototype index was examined across characteristics of the sample and compared to full EBP measures using generalized estimating equations.ResultsFive items were selected for inclusion in the prototype index representing the dimensions ofuse of research evidence, self-efficacy, resources, attitudes,andactivities. Testing demonstrated that the prototype behaves consistently regardless of age groups, gender, and setting, and provides comparable information to full EBP measures.ConclusionThis study provides promising preliminary evidence to justify continuing the index development process. The benefits of having a global index of EBP as opposed to having multiple domain-specific measures are discussed in this paper.