bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Thalamic and Intracortical Inhibitory Function of Somatosensory System Is Unchanged in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis
Authors: Akıncı Tuba , Gündüz Ayşegül , Özkara Çiğdem , Kızıltan Meral E. 
Published: March 2021

Purpose:In mesial temporal lobe epilepsy with hippocampal sclerosis, there is parietal atrophy and cognitive involvement in related domains. In this context, we hypothesized that inhibitory input into somatosensory cortex and thalamus may be increased in these patients, which could improve after epilepsy surgery. Thus, we analyzed the inhibitory function of somatosensory system by studying surround inhibition (SI) and recovery function of somatosensory evoked potentials in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.Methods:Nine patients with unoperated mesial temporal lobe epilepsy with hippocampal sclerosis, 10 patients who underwent epilepsy surgery, and 12 healthy subjects were included. For SI of somatosensory evoked potentials, we recorded somatosensory evoked potentials after stimulating median or ulnar nerve at wrist separately and after median and ulnar nerves simultaneously and calculated SI% in all participants. For recovery function of somatosensory evoked potentials, paired stimulation of median nerve at 40- and 100-millisecond intervals was performed. We compared the findings among groups. As a secondary analysis, we determined the outliers in the patient group and analyzed the relation to the clinical findings.Results:The mean SI% or recovery function was similar among three groups. However, there were five patients with SI loss on normal side in the patient group, which was related to the antiseizure drugs.Conclusions:In contrast to our hypothesis, both intracortical (SI) and thalamic/striatal (recovery function) inhibitory modulation of the somatosensory cortex was not altered in mesial temporal lobe epilepsy with hippocampal sclerosis and did not differ in surgical and nonsurgical groups.
EZH2 Abundance Regulated by UHRF1/UBE2L6/UBR4 Ubiquitin System is the Potential Therapeutic Target to Trigger Pigmented Phenotype in Melanoma
Authors: Abali Gamze Kuser , Zhang Youfang , Szeto Pacman , Zhao Peinan , Moghaddam Samar Masoumi , Leece Isobel , Huang Cheng , Cheung Jen , Ameratunga Malaka , Noguchi Fumihito , Andrews Miles , Wong Nicholas C. , Schittenhelm Ralf , Shackleton Mark 
Published: March 2021

ABSTRACTCellular heterogeneity in cancer is linked to disease progression and therapy response, although the mechanisms regulating distinct cellular states within tumours are not well understood. To address this, we identified melanin pigment content as a major source of phenotypic and functional heterogeneity in melanoma and compared RNAseq data from high (HPC) and low pigmented melanoma cells (LPC), revealing the polycomb repressor complex protein, EZH2, as a master regulator of these states. EZH2 protein, but not RNA expression, was found to be upregulated in LPCs and inversely correlated with melanin in pigmented patient melanomas. Surprisingly, conventional EZH2 methyltransferase inhibitors, GSK126 and EPZ6438, had no effect on LPC survival, clonogenicity and pigmentation, despite fully inhibiting methyltransferase activity. In contrast, EZH2 silencing by siRNA strategy or DZNep, MS1943 that reduces EZH2 protein levels, significantly inhibited cell growth in LPCs by hampering ribosome biogenesis. In addition, decline in EZH2 protein level induces pigmented cell phenotype by inducing melanin biosynthesis. Proteasomal inhibitor, MG132 treatment induced EZH2 protein levels in HPCs prompted us to look for differentially regulated ubiquitin system proteins in HPC vs LPCs. UBE2L6, E2 conjugating enzyme has been shown to be downregulated significantly in LPCs by UHRF1-mediated CpG methylation. Both biochemical assays and animal studies demonstrated that UBE2L6 expression decline, in turn, promotes EZH2 protein stability due to lack of ubiquitination on K381 residue in LPCs. UBR4 cooperates with UBE2L6 to facilitate this ubiquitination process. Targeting UHRF1/UBE2L6/UBR4 axis can be a better treatment option to trigger HPC state in melanoma in which conventional EZH2 inhibitors are ineffective.
Multiomics Analyses Reveal Dynamic Bioenergetic Pathways and Functional Remodeling of the Heart During Intermittent Fasting
Authors: Arumugam Thiruma V. , Alli-Shaik Asfa , Liehn Elisa A. , Selvaraji Sharmelee , Poh Luting , Rajeev Vismitha , Cho Yoonsuk , Cho Yongeun , Kim Jongho , Kim Joonki , Swa Hannah L. F. , Hao David Tan Zhi , Ratttanasopa Chutima , Fann David Yang-Wei , Mayan David Castano , Ng Gavin Yong-Quan , Baik Sang-Ha , Mallilankaraman Karthik , Gelderblom Mathias , Drummond Grant R. , Sobey Christopher G. , Kennedy Brian K. , Singaraja Roshni R. , Mattson Mark P. , Jo Dong-Gyu , Gunaratne Jayantha 
Published: March 2021

AbstractAimsIntermittent fasting (IF) reduces cardiovascular risk factors in animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction, but the underlying molecular mechanisms are unknown. To delineate molecular and cellular adaptations of the heart to IF, we carried out system-wide comprehensive analyses of proteome and phosphoproteome, complemented with transcriptome profiling, followed by functional analysis.Methods and resultsIn order to understand molecular and cellular remodeling of the heart during IF, we employed advanced mass spectrometry for system-wide profiling of the proteome and phosphoproteome of heart tissues obtained from mice maintained for 6 months on either daily 12- or 16-hour fasting, every-other-day fasting or ad libitum control feeding regimens. We also performed transcriptome analyses using RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. IF regimens significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Comparison of differentially expressed proteome and transcriptome upon IF showed the higher correlation of pathway alternation in short IF regimen but the inverse correlation of metabolic processes such as fatty acid oxidation and immune processes in longer IF regimens. In addition, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance.ConclusionOur systematic multi-omics study elucidates a molecular framework for understanding how IF impacts the heart’s function and its vulnerability to injury and disease.Translational perspectiveIntermittent fasting is emerging as a desirable lifestyle adaptation to impact cardiovascular health through the modulation of molecular and cellular mechanisms, and by acting on disease risk factors. Evidence from numerous studies indicates that the fasting cycles are highly and consistently effective in protecting against cardiovascular diseases and improving cardiac health in animals and human. Using multi-omics, here we dissect distinct molecular adaptations of the heart to different intermittent fasting regimens. Our results unveil novel cardioprotective mechanisms and open up new avenues for innovative pharmacological approaches to prevent and treat cardiovascular diseases.
Hypnotic visual hallucination induces greater lateralised brain activity than visual imagery
Authors: Lanfranco Renzo C. , Rivera-Rei Álvaro , Huepe David , Ibáñez Agustín , Canales-Johnson Andrés 
Published: March 2021

AbstractHypnotic suggestions can produce a broad range of perceptual experiences, including hallucinations. Visual hypnotic hallucinations differ in many ways from regular mental images. For example, they are usually experienced as automatic, vivid, and real images, typically compromising the sense of reality. While both hypnotic hallucination and mental imagery are believed to mainly rely on the activation of the visual cortex via top-down mechanisms, it is unknown how they differ in the neural processes they engage. Here we used an adaptation paradigm to test and compare top-down processing between hypnotic hallucination, mental imagery, and visual perception in very highly hypnotisable individuals whose ability to hallucinate was assessed. By measuring the N170/VPP event-related complex and using multivariate decoding analysis, we found that hypnotic hallucination of faces involves greater top-down activation of sensory processing through lateralised mechanisms in the right hemisphere compared to mental imagery. Our findings suggest that the neural signatures that distinguish hypnotically hallucinated faces from imagined faces lie in the right brain hemisphere.
An atypical class of non-coding small RNAs produced in rice leaves upon bacterial infection
Authors: Reshetnyak Ganna , Jacobs Jonathan M. , Auguy Florence , Sciallano Coline , Claude Lisa , Medina Clemence , Perez-Quintero Alvaro L. , Comte Aurore , Thomas Emilie , Bogdanove Adam , Koebnik Ralf , Szurek Boris , Dievart Anne , Brugidou Christophe , Lacombe Severine , Cunnac Sebastien 
Published: March 2021

ABSTRACTNon-coding small RNAs (sRNA) act as mediators of gene silencing and regulate plant growth, development and stress responses. Early insights into plant sRNAs established a role in antiviral defense and they are now extensively studied across plant-microbe interactions. Here, sRNA sequencing discovered a class of sRNA in rice (Oryza sativa) specifically associated with foliar diseases caused byXanthomonas oryzaebacteria.Xanthomonas-induced small RNAs (xisRNAs) loci were distinctively upregulated in response to diverse virulent strains at an early stage of infection producing a single duplex of 20-22nt sRNAs. xisRNAs production was dependent on the Type III secretion system, a major bacterial virulence factor for host colonization. xisRNA loci overlap with annotated transcripts sequences often encoding protein kinase domain proteins. A number of the corresponding ricecis-genes have documented functions in immune signaling and some xisRNA loci coincide with the coding sequence of a conserved kinase motif. xisRNAs exhibit features of small interfering RNAs and their biosynthesis depend on canonical componentsOsDCL1andOsHEN1.xisRNA induction possibly mediates post-transcriptional gene silencing but they do not broadly suppresscis-genes expression on the basis of mRNA-seq data. Overall, our results identify a group of unusual sRNAs with a potential role in plant-microbe interactions.
Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals
Authors: Trinité Benjamin , Pradenas Edwards , Marfil Silvia , Rovirosa Carla , Urrea Víctor , Tarrés-Freixas Ferran , Ortiz Raquel , Vergara-Alert Júlia , Segalés Joaquim , Guallar Victor , Lepore Rosalba , Izquierdo-Useros Nuria , Trujillo Glòria , Trapé Jaume , González-Fernández Carolina , Flor Antonia , Pérez-Vidal Rafel , Chamorro Anna , Paredes Roger , Blanco Ignacio , Grau Eulalia , Massanella Marta , Carrillo Jorge , Clotet Bonaventura , Blanco Julià 
Published: March 2021

AbstractTo assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7.FundingThis study was funded by Grifols, theDepartament de Salutof theGeneralitat de Catalunya, the Spanish Health Institute Carlos III, CERCA Programme/Generalitat de Catalunya, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos.
Transparent exploration of machine learning for biomarker discovery from proteomics and omics data
Authors: Torun Furkan M. , Winter Sebastian Virreira , Doll Sophia , Riese Felix M. , Vorobyev Artem , Mueller-Reif Johannes B. , Geyer Philipp E. , Strauss Maximilian T. 
Published: March 2021

AbstractBiomarkers are of central importance for assessing the health state and to guide medical interventions and their efficacy, but they are lacking for most diseases. Mass spectrometry (MS)-based proteomics is a powerful technology for biomarker discovery, but requires sophisticated bioinformatics to identify robust patterns. Machine learning (ML) has become indispensable for this purpose, however, it is sometimes applied in an opaque manner, generally requires expert knowledge and complex and expensive software. To enable easy access to ML for biomarker discovery without any programming or bioinformatic skills, we developed ‘OmicLearn’ (https://OmicLearn.com), an open-source web-based ML tool using the latest advances in the Python ML ecosystem. We host a web server for the exploration of the researcher’s results that can readily be cloned for internal use. Output tables from proteomics experiments are easily uploaded to the central or a local webserver. OmicLearn enables rapid exploration of the suitability of various ML algorithms for the experimental datasets. It fosters open science via transparent assessment of state-of-the-art algorithms in a standardized format for proteomics and other omics sciences.Graphical AbstractHighlightsOmicLearn is an open-source platform allows researchers to apply machine learning (ML) for biomarker discoveryThe ready-to-use structure of OmicLearn enables accessing state-of-the-art ML algorithms without requiring any prior bioinformatics knowledgeOmicLearn’s web-based interface provides an easy-to-follow platform for classification and gaining insights into the datasetSeveral algorithms and methods for preprocessing, feature selection, classification and cross-validation of omics datasets are integratedAll results, settings and method text can be exported in publication-ready formats
Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin
Authors: Ylösmäki Erkko , Martins Beatriz , Fusciello Manlio , Feola Sara , Hamdan Firas , Chiaro Jacopo , Ylösmäki Leena , Vaughan Matthew J. , Viitala Tapani , Kulkarni Prasad S. , Cerullo Vincenzo 
Published: March 2021

AbstractIntratumoural bacillus Calmette-Guérin (BCG) therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumour. Here, we have developed a novel cancer vaccine platform based on BCG that can direct BCG-induced immune responses against tumour antigens. By physically attaching tumour-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoural T cell-specific immune responses towards the attached tumour antigens. These therapeutic peptides can be attached to the mycobacterial outer membrane using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat, N-terminally fused to the tumour-specific peptides. Alternatively, therapeutic peptides can be conjugated with a poly-lysine sequence N-terminally fused to the tumour-specific peptides. Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the anti-tumour responses of BCG can be significantly improved by coating the BCG with tumour-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-PD-1 immune checkpoint inhibitor therapy, the number of responders to anti-PD-1 immunotherapy can be significantly increased.
Gut markers of bodily self-consciousness
Authors: Monti Alessandro , Porciello Giuseppina , Panasiti Maria Serena , Aglioti Salvatore M. 
Published: March 2021

AbstractBodily self-consciousness, the state of mind that allows humans to be aware of their own body, forms the backdrop for almost every human experience, yet its underpinnings remain elusive. Here we combine an ingestible, minimally invasive capsule with surface electrogastrography to probe if gut physiology correlates with bodily self-consciousness during a virtual bodily illusion. We discover that specific patterns of stomach and bowel activity (temperature, pressure, pH, and gastric peak frequency) covary with specific facets of bodily self-consciousness (feelings of body agency, location, and disembodiment). These results uncover the hitherto untapped potential of minimally invasive probes to study the link between mental and gut states, and reveal a deep visceral pathway to the self-conscious perception of ourselves as embodied beings.
Neutralization heterogeneity of United Kingdom and South-African SARS-CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers
Authors: Marot Stéphane , Malet Isabelle , Jary Aude , Leducq Valentin , Abdi Basma , Teyssou Elisa , Soulie Cathia , Wirden Marc , Rodriguez Christophe , Fourati Slim , Pawlotsky Jean-Michel , Boutolleau David , Burrel Sonia , Calvez Vincent , Marcelin Anne-Geneviève 
Published: March 2021

ABSTRACTThere are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, most of the sera harbored at least a NAb titer ≥ 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.
The effect of disturbance and drought on Hairy Jointgrass (Arthraxon hispidus) in north coast New South Wales: Understanding threatened species populations in a dynamic landscape
Authors: White Laura , Catterall Claudia , Taffs Kathryn 
Published: March 2021

AbstractEcological disturbances such as fire, grazing or mechanical cultivation can promote or suppress plant populations within vegetation communities. Therefore, such processes can threaten vulnerable species, or play a significant role in their conservation, so an understanding of a species’ ecological response to disturbance is foundational to threatened species management. Various types of anthropogenic disturbance are listed as threats to the vulnerable‐listed Arthraxon hispidus (Hairy Jointgrass) (Poaceae) in NSW; however, there is evidence that slashing, grazing and fire can stimulate the recruitment and establishment of this annual species in some circumstances. We undertook field experiments to investigate the effects of each of these disturbance regimes on A. hispidus populations over two growing seasons within modified wetlands/moist pastures in north coast NSW. We found that the application of fire in winter had a stronger promotional effect on A. hispidus recruitment than slashing, though both treatments increased its abundance and reduced the height and cover of surrounding vegetation, particularly exotic perennial grasses. Following initial establishment, A. hispidus declined under drought conditions during the study, and continuous grazing exacerbated this effect. Drought also increased the abundance of introduced species relative to native wetland species across the study sites. Results confirm that disturbance, particularly fire, can promote A. hispidus populations in some vegetation communities; however, climatic variation also plays a role in its population dynamics. Consideration of each of these factors and their potential interactions is important when developing conservation approaches for this threatened species.
Pregnancy outcomes following gestational exposure to papaverine: An observational comparative study
Authors: Gueta Itai , Braun Adi , Gilan Adi , Berlin Maya , Kohn Elkana , Barchel Dana , Markovits Noa , Berkovitch Matitiahu , Loebstein Ronen 
Published: March 2021

AimsPapaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death.MethodsA retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database.ResultsThe study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P < .001), CS (35.9 vs. 24.1%, P < .001) and lower birth weight (3207 vs. 3246 g, P = .02). Adjustment for treatment indication demonstrated that these remained significant only when given for obstetrical/surgical aetiologies. Comparable rates were observed for the remaining outcomes.ConclusionsShort‐term gestational exposure to papaverine adjusted for indication was not associated with preterm deliveries, CS, lower birthweight, small for gestational age or perinatal death. Rate of major malformations among 46 first trimester exposures was comparable to controls.
Influence of prenatal perceived stress on postpartum weight retention is mediated by high gestational weight gain in women with overweight
Authors: Leonard Krista S. , Adams Elizabeth L. , Savage Jennifer S. , Paul Ian M. , Kraschnewski Jennifer L. , Pattison Krista L. , Kjerulff Kristen H. , Symons Downs Danielle 
Published: March 2021

SummaryWomen with excessive gestational weight gain (GWG) are at risk for poor psychosocial well‐being and postpartum weight retention (PPWR). Scant research has examined longitudinal interrelations of GWG, psychosocial factors, and PPWR. This study examined: (a) pre‐pregnancy weight status (ie, normal, overweight, obesity) differences in PPWR and its psychosocial determinants (perceived social support, perceived stress, depression) in women with excessive GWG (ie, above 2009 Institute of Medicine guidelines); and (b) whether GWG mediated associations between psychosocial determinants and PPWR. Women (N = 1352) reported third trimester perceived social support, perceived stress, and depressive symptoms, GWG, and 6‐ and 12‐month PPWR via telephone interviews. Multivariate ANOVA analyses showed women with normal weight had higher 6‐month PPWR than women with obesity; univariate ANOVA showed no group differences in psychosocial factors. Hayes mediation analyses indicated that GWG mediated the association between perceived stress and PPWR in women with overweight but not women with normal weight or obesity; perceived stress predicted GWG, and in turn, PPWR. Prenatal perceived stress may be a modifiable target of GWG and PPWR. Future research is needed to examine the utility of tailoring perinatal weight regulation interventions to reduce perceived stress in pregnant women with overweight.