bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing of multiepitope-based vaccine against Leptospirosis using Immuno-Informatics approaches
Authors: Abdullah Mohd , Kadivella Mohammad , Sharma Rolee , Faisal Syed M. , Azam Sarwar 
Published: February 2021

AbstractLeptospirais a zoonotic pathogen causing significant morbidity and mortality both in animals and humans. Although several surface proteins have been identified as vaccine candidate, they failed to induce sterilizing immunity and cross protection against different serovars. Thus, identification of highly immunogenic antigens that are conserved among pathogenic serovars would be first step towards development of universal vaccine for Leptospirosis. Here we used reverse vaccinology pipeline to screen core genome of pathogenicLeptospiraspp.in order to identify suitable vaccine candidates. Based on properties like sub cellular localization, adhesin, homology to human proteins, antigenicity and allergenicity, 18 antigenic proteins were identified and were further investigated for immunological properties. Based on immunogenicity, Protegenicity, Antigenicity, B-cell and promiscuous T-cell epitopes, 6 Potential Vaccine Candidates (PVCs) were finally selected which covered most of the affected world population. For designing a Multi-Epitope Vaccine (MEV), 6 B-cell and 6 promiscuous MHC-I and MHC-II epitopes from each candidate were clustered with linkers in between and stitched along with a TLR4 adjuvant (APPHALS) at the N-terminal to form a construct of 361 amino acids. The physiochemical properties, secondary and tertiary structure analysis revealed that MEV was highly stable. Molecular docking analysis revealed the deep binding interactions of the MEV construct within the grooves of human TLR4 (4G8A). In-silico codon optimization and cloning of the vaccine construct assured good expression. Further, immune simulations have shown that MEV could induce strong and diverse B and T cell responses. Taken together our results indicate that the designed MEV could be a promising subunit vaccine candidate against Leptospirosis, however it requires experimental validation.
improv: A software platform for real-time and adaptive neuroscience experiments
Authors: Draelos Anne , Loring Matthew D. , Nikitchenko Maxim , Sriworarat Chaichontat , Gupta Pranjal , Sprague Daniel Y. , Pnevmatikakis Eftychios , Giovannucci Andrea , Benster Tyler , Deisseroth Karl , Pearson John M. , Naumann Eva A. 
Published: February 2021

AbstractCurrent neuroscience research is often limited to testing predetermined hypotheses and post hoc analysis of already collected data. Adaptive experimental designs, in which modeling drives ongoing data collection and selects experimental manipulations, offer a promising alternative. Still, tight integration between models and data collection requires coordinating diverse hardware configurations and complex computations under real-time constraints. Here, we introduceimprov, a software platform that allows users to fully integrate custom modeling, analysis, and visualization with data collection and experimental control. We demonstrate bothin silicoandin vivohowimprovenables more efficient experimental designs for discovery and validation across various model organisms and data types.Improvcan orchestrate custom real-time behavioral analyses, rapid functional typing of neural responses from large populations via calcium microscopy, and optimal visual stimulus selection. We incorporate real-time machine learning methods for dimension reduction and predictive modeling of latent neural and behavioral features. Finally, we demonstrate howimprovcan perform model-driven interactive imaging and simultaneous optogenetic photostimulation of visually responsive neurons in the larval zebrafish brain expressing GCaMP6s and the red-shifted opsin rsChRmine. Together, these results demonstrate the power ofimprovto integrate modeling with data collection and experimental control to achieve next-generation adaptive experiments.
Astrocyte-derived TNF and glutamate critically modulate microglia reactivity by methamphetamine
Authors: Canedo Teresa , Portugal Camila Cabral , Socodato Renato , Bravo Joana , Almeida Tiago Oliveira , Magalhães João D. , Guerra-Gomes Sónia , Oliveira João Filipe , Sousa Nuno , Magalhães Ana , Relvas João Bettencourt , Summavielle Teresa 
Published: February 2021

AbstractMethamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation that contributes to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders linked to cognitive impairment and neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in human Meth abusers), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a manner dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production or suppressing astrocytic calcium mobilization prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth exposure. Overall, our data indicate that glial crosstalk is critical to relay behavioral alterations caused by acute Meth exposure.One Sentence SummaryGlial crosstalk under methamphetamine exposure
The last battle of Anne of Brittany: solving mass grave through an interdisciplinary approach (paleopathology, anthropobiology, history, multiple isotopes and radiocarbon dating)
Authors: Colleter Rozenn , Bataille Clément , Dabernat Henri , Pichot Daniel , Hamon Philippe , Duchesne Sylvie , Labaune-Jean Françoise , Jean Stéphane , Cloirec Gaétan Le , Milano Stefania , Trost Manuel , Steinbrenner Sven , Marchal Marine , Guilbeau-Frugier Céline , Telmon Norbert , Crubézy Éric , Jaouen Klervia 
Published: February 2021

AbstractMass graves are usually key historical markers with strong incentive for archeological investigations. The identification of individuals buried in mass graves has long benefitted from traditional historical, archaeological, anthropological and paleopathological techniques. The addition of novel methods including genetic, genomic and isotopic geochemistry have renewed interest in solving unidentified mass graves. In this study, we demonstrate that the combined use of these techniques allows the identification of the individuals found in two Breton historical mass graves, where one method alone would not have revealed the importance of this discovery. The skeletons likely belong to soldiers from the two enemy armies who fought during a major event of Breton history: the siege of Rennes in 1491, which ended by the wedding of the Duchess of Brittany with the King of France and signaled the end of the independence of the region. Our study highlights the value of interdisciplinary approaches with a particular emphasis on increasingly accurate isotopic markers. The development of the sulfur isoscape and testing of the triple isotope geographic assignment are detailed in a companion paper [1].
How human runners regulate footsteps on uneven terrain
Authors: Dhawale Nihav , Venkadesan Madhusudhan 
Published: February 2021

AbstractRunning stably on uneven natural terrain takes skillful control and was critical for human evolution. Even as runners circumnavigate hazardous obstacles such as steep drops, they must contend with uneven ground that is gentler but still destabilizing. We do not know how footsteps are guided based on the uneven topography of the ground and how those choices influence stability. Therefore, we studied human runners on trail-like undulating uneven terrain and measured their energetics, kinematics, ground forces, and stepping patterns. We find that runners do not selectively step on more level ground areas. Instead, the body’s mechanical response, mediated by the control of leg compliance, helps maintain stability without requiring precise regulation of footsteps. Furthermore, their overall kinematics and energy consumption on uneven terrain showed little change from flat ground. These findings may explain how runners remain stable on natural terrain while devoting attention to tasks besides guiding footsteps.
The Optimum Cut-off Value of the Nelwan Score to Diagnose Typhoid Fever in Adults
Authors: Nelwan Erni Juwita , Paramita Luh Putu Listya , Sinto Robert , Hosea Fransiscus Nikodemus , Nugroho Pringgodigdo , Pohan Herdiman T. 
Published: February 2021

AbstractIntroductionTyphoid fever can be challenging to diagnose since clinicians often depend merely on clinical presentation. Clinical scores are useful to provide more accurate diagnosis. Variables in Nelwan Score are derived from clinical signs and symptoms of suspected cases for typhoid. Diagnostic value of Nelwan Score based on a cut-off value has never been evaluated.MethodsA cross sectional study was conducted between July 2017 and January 2018 in five hospitals and two Primary Health Centers in Jakarta and Tangerang. The inclusion criteria were patients with 3-14 days of fever and gastrointestinal symptoms between July 2017 and January 2018. Diagnosis are confirmed by blood culture, rectal swab culture, or PCR. Cut-off analysis was performed by using Receiver Operating Characteristic (ROC) curve and diagnostic value was analyzed to generate sensitivity, specificity, predictive value and likelihood ratio.ResultFrom 233 subjects involved, 4.72% of them were confirmed to have typhoid fever. The optimal cut-off value of Nelwan Score is 10 with AUC 71.3%. This cut-off value has sensitivity 81.8%, specificity 60.8%, PPV 9.3%, NPV 98.5%, LR + 2.086, and LR – 0.299.ConclusionNelwan Score with cut-off value of 10 provides a good diagnostic performance as a screening tool for patients with suspected typhoid fever clinical presentation.
ERICA: Emulated Retinal Image CApture - A tool for testing, training and validating retinal image processing methods
Authors: Young Laura K , Smithson Hannah E 
Published: February 2021

ABSTRACTHigh resolution retinal imaging systems, such as adaptive optics scanning laser ophthalmoscopes (AOSLO), are increasingly being used for clinical and fundamental studies in neuroscience. These systems offer unprecedented spatial and temporal resolution of retinal structuresin vivo. However, a major challenge is the development of robust and automated methods for processing and analysing these images. We present ERICA (Emulated Retinal Image CApture), a simulation tool that generates realistic synthetic images of the human cone mosaic, mimicking images that would be captured by an AOSLO, with specified image quality and with corresponding ground truth data. The simulation includes a self-organising mosaic of photoreceptors, the eye movements an observer might make during image capture, and data capture through a real system incorporating diffraction, residual optical aberrations and noise. The retinal photoreceptor mosaics generated by ERICA have a similar packing geometry to human retina, as determined by expert labelling of AOSLO images of real eyes. In the current implementation ERICA outputs convincingly realisticen faceimages of the cone photoreceptor mosaic but extensions to other imaging modalities and structures are also discussed. These images and associated ground-truth data can be used to develop, test and validate image processing and analysis algorithms or to train and validate machine learning approaches. The use of synthetic images has the advantage that neither access to an imaging system, nor to human participants is necessary for development.
Diffuse optical reconstructions of fNIRS data using Maximum Entropy on the Mean
Authors: Cai Zhengchen , Machado Alexis , Chowdhury Rasheda Arman , Spilkin Amanda , Vincent Thomas , Aydin Ümit , Pellegrino Giovanni , Lina Jean-Marc , Grova Christophe 
Published: February 2021

AbstractFunctional near-infrared spectroscopy (fNIRS) measures the hemoglobin concentration changes associated with neuronal activity. Diffuse optical tomography (DOT) consists of reconstructing the optical density changes measured from scalp channels to the oxy-/deoxy-hemoglobin (i.e., HbO/HbR) concentration changes within the cortical regions. In the present study, we adapted a nonlinear source localization method developed and validated in the context of Electro- and Magneto-Encephalography (EEG/MEG): the Maximum Entropy on the Mean (MEM), to solve the inverse problem of DOT reconstruction. We first introduced depth weighting strategy within the MEM framework for DOT reconstruction to avoid biasing the reconstruction results of DOT towards superficial regions. We also proposed a new initialization of the MEM model improving the temporal accuracy of the original MEM framework. To evaluate MEM performance and compare with widely used depth weighted Minimum Norm Estimate (MNE) inverse solution, we applied a realistic simulation scheme which contained 4000 simulations generated by 250 different seeds at different locations and 4 spatial extents ranging from 3 to 40cm2along the cortical surface. Our results showed that overall MEM provided more accurate DOT reconstructions than MNE. Moreover, we found that MEM was remained particularly robust in low signal-to-noise ratio (SNR) conditions. The proposed method was further illustrated by comparing to functional Magnetic Resonance Imaging (fMRI) activation maps, on real data involving finger tapping tasks with two different montages. The results showed that MEM provided more accurate HbO and HbR reconstructions in spatial agreement with the main fMRI cluster, when compared to MNE.HighlightsWe introduced a new fNIRS reconstruction method - Maximum Entropy on the Mean.We implemented depth weighting strategy within the MEM framework.We improved the temporal accuracy of the original MEM reconstruction.Performances of MEM and MNE were evaluated with realistic simulations and real data.MEM provided more accurate and robust reconstructions than MNE.
The amyloid concentric β-barrel hypothesis: models of Synuclein oligomers, annular protofibrils, lipoproteins, and transmembrane channels
Authors: Durell Stewart R. , Guy H. Robert 
Published: February 2021

AbstractAmyloid beta (Aβ of Alzheimer’s disease) and α-synuclein (α-Syn of Parkinson’s disease) form large fibrils. Evidence is increasing however that much smaller oligomers are more toxic and that these oligomers can form transmembrane ion channels. We have proposed previously that Aβ42 oligomers, annular protofibrils, and ion channels adopt concentric β-barrel molecular structures. Here we extend that hypothesis to the superfamily of α, β, and γ-synucleins. Our models of numerous Synuclein oligomers, annular protofibrils, tubular protofibrils, lipoproteins, and ion channels were developed to be consistent with sizes, shapes, molecular weights, and secondary structures of assemblies as determined by EM and other studies. The models have the following features: 1) all subunits have identical structures and interactions; 2) they are consistent with conventional β-barrel theory; 3) the distance between walls of adjacent β-barrels is between 0.6 and 1.2 nm; 4) hydrogen bonds, salt bridges, interactions among aromatic side-chains, burial and tight packing of hydrophobic side-chains, and aqueous solvent exposure of hydrophilic side-chains are relatively optimal; and 5) residues that are identical among distantly related homologous proteins cluster in the interior of most oligomers whereas residues that are hypervariable are exposed on protein surfaces. Atomic scale models of some assemblies were developed.
Human immunocompetent Organ-on-Chip platforms allow safety profiling of tumor-targeted T-cell bispecific antibodies
Authors: Kerns S. Jordan , Belgur Chaitra , Petropolis Debora B. , Barrile Riccardo , Kanellias Marianne , Sam Johannes , Weinzierl Tina , Fauti Tanja , Freimoser-Grundschober Anne , Eckmann Jan , Hage Carina , Geiger Martina , Ng Patrick , Tien-Street William , Manatakis Dimitris V. , Micallef Virginie , Gerard Régine , Bscheider Michael , Breous-Nystrom Ekaterina , Schneider Anneliese , Giusti Anna-Maria , Bertinetti-Lapatki Cristina , Grant Heather S. , Roth Adrian B. , Hamilton Geraldine A. , Singer Thomas , Karalis Katia , Moisan Annie , Bruenker Peter , Klein Christian , Bacac Marina , Gjorevski Nikolce , Cabon Lauriane 
Published: February 2021

AbstractTraditional drug safety assessment often fails to predict complications in humans, especially when the drug targets the immune system. Here, we show the unprecedented capability of two Organs-on-Chips to evaluate the safety profile of T-cell bispecific antibodies (TCBs) targeting tumor antigens. Although promising for cancer immunotherapy, TCBs are associated with an on-target, off-tumor risk due to low levels of expression of tumor antigens in healthy tissues. We leveraged in vivo target expression and toxicity data of TCBs targeting folate receptor 1 (FOLR1) or carcinoembryonic antigen (CEA) to design and validate human immunocompetent Organs-on-Chips safety platforms. We discovered that the Lung-Chip and Intestine-Chip could reproduce and predict target-dependent TCB safety liabilities, based on sensitivity to key determinants thereof, such as target expression and antibody affinity. These novel tools broaden the research options available for mechanistic understandings of engineered therapeutic antibodies and assessing safety in tissues susceptible to adverse events.
Male mate choice unresolved in the mangrove rivulus
Authors: Gresham Jennifer D. , Bowman Sarah N. , Keck Chloe M.T. , Quertermous Haylee M. , Earley Ryan L. 
Published: February 2021

AbstractMate choice has the potential to drive phenotypic evolution because it can determine traits that increase an individual’s likelihood to reproduce (courtship behaviors, elaborate ornamentation). These traits, however, can also be detrimental for health or survival, often antagonizing the evolution of extreme phenotypes. Mangrove rivulus fish (Kryptolebias marmoratus) develop as self-fertilizing simultaneous hermaphrodites. Hermaphrodites overwhelmingly self-fertilize their eggs internally, but occasionally oviposit unfertilized eggs. Some individuals change sex to male after sexual maturity, essentially forgoing the reproductive assurance of selfing. In a continuing effort to understand how sex change to male is maintained this species, I designed an experiment to determine whether males act as choosers to increase their likelihood of finding unfertilized eggs for reproduction. I hypothesized that males would prefer to associate with younger hermaphrodites when given a dichotomous choice, as they lay a greater proportion of unfertilized eggs compared to older hermaphrodites. The males in this study did not show a preference for either the younger or older hermaphrodite but exhibited greater within individual variance across subtrials than among individual variation. I discuss alternative hypotheses concerning male mate choice in mangrove rivulus, which may illuminate hypotheses to be tested in this and other hermaphroditic species.
Surfactin stimulated by pectin molecular patterns and root exudates acts as a key driver ofBacillus-plant mutualistic interaction
Authors: Hoff Grégory , Arguelles-Arias Anthony , Boubsi Farah , Prsic Jelena , Meyer Thibault , Ibrahim Heba M. M. , Steels Sebastien , Luzuriaga Patricio , Legras Aurélien , Franzil Laurent , Lequart Michelle , Rayon Catherine , Osorio Victoria , de Pauw Edwin , Lara Yannick , Deboever Estelle , de Coninck Barbara , Jacques Philippe , Deleu Magali , Petit Emmanuel , Van Wuytswinkel Olivier , Ongena Marc 
Published: February 2021

AbstractBacillus velezensisis considered as model species belonging to the so-calledB. subtiliscomplex that typically evolved to dwell in the soil rhizosphere niche and establish intimate association with plant roots. This bacterium provides protection to its natural host against diseases and represents one of the most promising biocontrol agents. However, the molecular basis of the cross-talk that this bacterium establishes with its natural host has been poorly investigated. We show here that these plant-associated bacteria have evolved some polymer-sensing system to perceive their host and that in response, they increase the production of the surfactin-type lipopeptide. Furthermore, we demonstrate that surfactin synthesis is favoured upon growth on root exudates and that this lipopeptide is a key component used by the bacterium to optimize biofilm formation, motility and early root colonization. In this specific nutritional context, the bacterium also modulates qualitatively the pattern of surfactin homologues co-producedin plantaand mainly forms variants that are the most active at triggering plant immunity. Surfactin represents a shared good as it reinforces the defensive capacity of the host.ImportanceWithin the plant-associated microbiome, some bacterial species are of particular interest due to the disease protective effect they provide via direct pathogen suppression and/or stimulation of host immunity. While these biocontrol mechanisms are quite well characterized, we still poorly understand the molecular basis of the cross talk these beneficial bacteria initiate with their host. Here we show that the model speciesBacillus velezensisstimulates production of the surfactin lipopeptide upon sensing pectin as cell surface molecular pattern and upon feeding on root exudates. Surfactin favors bacterial rhizosphere fitness on one hand and primes the plant immune system on the other hand. Our data therefore illustrate how both partners use this multifunctional compound as unique shared good to sustain mutualistic interaction.
NF-κB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly via P450scc/SOD2 deacetylation during spermatogenesis
Authors: Wang Mei , Zeng Ling , Xiong Yao , Wang Xiao-fei , Cheng Lin , Wang Fang , Su Ping , Zhang Yuan-zhen 
Published: February 2021

AbstractTesticular homeostasis requires the balanced interplay between specific molecules in Sertoli cells, Leydig cells, germ cells. Loss of this coordination can lead to the disruption of spermatogenesis, even male infertility. By operating the upregulation and downregulation of Sirt3 in our male subfertility rats model and two testicular cells models, we indicated that Sirt3 overexpression and activator ameliorated cholesterol metabolism via P450scc deacetylation in Leydig cells, and cytoskeleton assembly via PDLIM1 with SOD2 deacetylation in Sertoli cells and elongating spermatids. In terms of the upstream regulator of Sirt3, the phosphorylation of NF-κB p65Ser536stimulated the nuclear translocation of NF-κB subunits (p50, p65, RelB), which bound to TFBS1 and TFBS2 synchronously in the promoter of Sirt3, repressing Sirt3 transcription. This study demonstrates that NF-κB-repressed SIRT3 acts directly on cholesterol metabolism of Leydig cells and cytoskeleton assembly of Sertoli cells via P450scc/SOD2 deacetylation to regulate sperm differentiation, influencing spermatogenesis, even male fertility.Research organism: Rat, mouse