bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN VITROANTI-VIRAL ACTIVITY OF HEXETIDINE (BACTIDOL®) ORAL MOUTHWASH AGAINST HUMAN CORONAVIRUS OC43 AND INFLUENZA A (H1N1) VIRUS
Authors: Tobias -Altura Marohren C , Ngelangel Corazon A 
Published: February 2021

ABSTRACTMouthwashes are used to decrease oral cavity microbial load due to their antiseptic properties. Hexetidine is a broad-spectrum antiseptic used for minor infections of mucous membranes, and in particular as a 0.1% mouthwash for local infections and oral hygiene.This study determined the anti-viral activity of the mouthwash hexetidine (Bactidol®), specifically in reducing viral concentration of Human Coronavirus OC43 (HCoV OC43; ATCC®VR-1558™) and Influenza A virus (IAV H1N1; clinical strain) in Vero 6 and MDCK cell cultures respectively, using in-vitro suspension assay (ASTM E-1052-11) designed to evaluate virucidal property of microbicides like hexetidine.Study results indicated that hexetidine was able to reduce infectivity of HCoV OC43 and IAV H1N1 at 25%, 50% and 100% concentrations by more than 80% at 15- and 30-seconds exposure times. One hundred percent (100%) concentration of hexetidine was found to be cytotoxic to MDCK cell line used for IAV H1N1 propagation. Hexetidine-treated cell lines achieved >80% survival rate for MDCK and Vero E6 at a contact time of 15 seconds and 30 seconds (which are the approximate times of gargling with hexetidine mouthwash).The anti-viral activity of hexetidine mouthwash against other more virulent or pathogenic coronaviruses like SARS-CoV-2 can be explored further.
Locomotor performance and CNS responses to hypoxia in a cyclic nucleotide-gated channel mutant of adultDrosophila
Authors: Qiu Shuang , Xiao Chengfeng , Robertson R Meldrum 
Published: February 2021

AbstractDrosophilaprovides an excellent opportunity to explore the genetic basis for behavioral and CNS responses to hypoxia. Cyclic guanosine monophosphate (cGMP) modulates the speed of recovery from anoxia in adults and mediates hypoxia-related behaviors in larvae. Cyclic nucleotide-gated channels (CNG) and cGMP-activated protein kinase (PKG) are two cGMP downstream targets. PKG is involved in behavioral tolerance to hypoxia and anoxia in adults, however little is known about CNG channels. We used a CNGL mutant with reducedCNGLtranscripts to investigate the contribution of CNGL to the hypoxia response. In control flies (w1118), hypoxia immediately reduced path length per minute in a locomotor assay. Flies took 30-40 mins in air to recover from 15 mins hypoxia. CNGL mutants had reduced locomotion under normoxia and impaired recovery from hypoxia, similar to the effects of pan-neuralCNGLknockdown. In the CNGL mutants hypoxia caused an acute increase in path length per minute followed by a gradual increase during hypoxia. Basal levels of CNS extracellular K+concentrations were reduced in the mutants. In response to hypoxia, the mutants had an increased extracellular K+concentration change, reduced time to reach the K+concentration peak, and delayed recovery time. Genetic manipulation to increase cGMP in the CNGL mutants eliminated the impairment of recovery from hypoxia and partially compensated for the effects of hypoxia on CNS K+. Although the neural mechanisms have yet to be determined, CNGL channels and cGMP signaling are involved in the hypoxia response of adultDrosophila.
Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection
Authors: Quiroga-Martinez D.R. , Hansen N. C. , Højlund A. , Pearce M. , Brattico E. , Holmes E. , Friston K. , Vuust P 
Published: February 2021

AbstractWhen listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in synaptic efficacy underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)—and its modulation by context predictability and musical expertise—are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)—typically related to gain control—or extrinsic connections between A1 and STG—typically related to propagation of prediction and error signals—better explained magnetoencephalography (MEG) responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing.Significance statementIn complex auditory contexts, being able to identify informative signals is of paramount importance. Such is the case of music listening, where surprising sounds play a fundamental role in its perceptual, aesthetical, and emotional experience. Crucially, surprising sounds in the pitch dimension are more easily detected and generate stronger cortical responses when melodies are predictable and when the listener is a musician. Using Dynamic Causal Modelling, here we show that such effects arise from a local increase in neural gain within auditory areas, rather than from passing of prediction and error signals between brain regions. Consistent with predictive processing theories, this suggests that the enhanced precision of auditory predictive models—through melodic predictability and musical training—up-regulates the processing of informative error signals in the brain.
Using a Human Circulation Mathematical Model to Simulate the Effects of Hemodialysis and Therapeutic Hypothermia
Authors: Joseph Jermiah J. , Hunter Timothy J. , Sun Clara , Goldman Daniel , Kharche Sanjay R. , McIntyre Christopher W. 
Published: February 2021

AbstractBackgroundThe human blood circulation is an intricate process regulated by multiple biophysical factors. Our patients often suffer from renal disease and atrial fibrillation, and are given treatments such as therapeutic hypothermia, exercise, and hemodialysis. In this work, a hemodynamic mathematical model of human circulation coupled to a representative dialysis machine is developed and used to explore causal mechanisms of our recent clinical observations.MethodsAn ordinary differential equation model consisting of human whole body circulation, baroreflex control, and a hemodialysis machine was implemented. Experimentally informed parameter alterations were used to implement hemodialysis and therapeutic hypothermia. By means of parameter perturbation, four model populations encompassing baseline, dialysed, hypothermia treated, and simultaneous dialysed with hypothermia were generated. In model populations, multiple conditions including atrial fibrillation, exercise, and renal failure were simulated. The effects of all conditions on clinically relevant non-invasive measurables such as heart rate and blood pressure were quantified. A parameter sensitivity analysis was implemented to rank model output influencing parameters in the presented model.ResultsResults were interpreted as alterations of the respective populations mean values and standard deviations of the clinical measurables, both in relation to the baseline population. A clinical measurable’s smaller standard deviation (in comparison to baseline population) was interpreted as a stronger association between a given clinical measure and the corresponding underlying process, which may permit the use of deducing one by observation of the other.The modelled dialysis was observed to increase systolic blood pressure, vessel shear, and heart rate. Therapeutic hypothermia was observed to reduce blood pressure as well as the intra-population standard deviation (heterogeneity) of blood flow in the large (aorta) and small (kidney) vasculature. Therapeutic hypothermia reduced shear in vessels, suggesting a potential benefit with respect to endothelial dysfunction and maintenance of microcirculatory blood flow. The action of therapeutic hypothermia under conditions such as atrial fibrillation, exercise, and renal failure was to reduce total blood flow, which was applicable in all simulated populations. Therapeutic hypothermia did not affect the dialysis function, but exercise improved the efficacy of dialysis by facilitating water removal.ConclusionsThis study illuminates some mechanisms of action for therapeutic hypothermia. It also suggests clinical measurables that may be used as surrogates to diagnose underlying diseases such as atrial fibrillation.
Phenotypic analysis of catastrophic childhood epilepsy genes: The Epilepsy Zebrafish Project
Authors: Griffin Aliesha , Carpenter Colleen , Liu Jing , Paterno Rosalia , Grone Brian , Hamling Kyla , Moog Maia , Dinday Matthew T. , Figueroa Francisco , Anvar Mana , Ononuju Chinwendu , Qu Tony , Baraban Scott C. 
Published: February 2021

AbstractGenetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes;ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADAandSTXBP1. A unifying epilepsy classification scheme was developed based on local field potential recordings and blinded scoring from ~3300 larvae. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.
Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells
Authors: Chevreau R. , Ghazale H , Ripoll C , Chalfouh C , Delarue Q , Hemonnot-Girard A.L. , Hirbec H , Wahane S , Perrin F , Noristani H , Guerout N , Hugnot JP 
Published: February 2021

AbstractEpendymal cells with stem cell properties reside in the adult spinal cord around the central canal. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, six of them more than 20 fold, namelyCrym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr. OSMR is the receptor for the inflammatory cytokine oncostatin (OSM) and we studied its regulation and role using neurospheres derived from ependymal cells. We found that OSM induces strong OSMR and p-STAT3 expression together with proliferation reduction and astrocytic differentiation. Conversely, production of oligodendrocyte-lineage OLIG1+cells was reduced. OSM is specifically expressed by microglial cells and was strongly upregulated after injury. We observed microglial cells apposed to ependymal cells in vivo and co-cultures experiments showed that these cells upregulate OSMR in neurosphere cells. Collectively, these results support the notion that microglial cells and OSMR/OSM pathway regulate ependymal cells in injury. In addition, the generated high throughput data provides a unique molecular resource to study how ependymal cell react to spinal cord lesion.
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
Authors: Planas Delphine , Bruel Timothée , Grzelak Ludivine , Guivel-Benhassine Florence , Staropoli Isabelle , Porrot Françoise , Planchais Cyril , Buchrieser Julian , Rajah Maaran Michael , Bishop Elodie , Albert Mélanie , Donati Flora , Behillil Sylvie , Enouf Vincent , Maquart Marianne , Gonzalez Maria , De Sèze Jérôme , Péré Hélène , Veyer David , Sève Aymeric , Simon-Lorière Etienne , Fafi-Kremer Samira , Stefic Karl , Mouquet Hugo , Hocqueloux Laurent , van der Werf Sylvie , Prazuck Thierry , Schwartz Olivier 
Published: February 2021

AbstractSARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.
Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation
Authors: Hegre Siv Anita , Samdal Helle , Klima Antonin , Stovner Endre B. , Nørsett Kristin G. , Liabakk Nina Beate , Olsen Lene Christin , Chawla Konika , Aas Per Arne , Sætrom Pål 
Published: February 2021

AbstractProper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 59 lncRNAs. We selected four of these lncRNAs –AC005682.5, RP11-132A1.4, ZFAS1, andEPB41L4A-AS1– for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.
Recurrent Vulvovaginal Candidiasis; a dynamic interkingdom biofilm disease ofCandidaandLactobacillus
Authors: McKloud Emily , Sherry Leighann , Kean Ryan , Delaney Christopher , Williams Shanice , Metcalfe Rebecca , Thomas Rachael , Williams Craig , Ramage Gordon 
Published: February 2021

AbstractVulvovaginal Candidiasis (VVC) is the most prevalentCandidainfection in humans affecting 75% of women at least once throughout their lifetime. In its debilitating recurrent form, RVVC is estimated to affect 140 million women annually. Despite this strikingly high prevalence, treatment options for RVVC remain limited with many women experiencing failed clinical treatment with frontline azoles. Further, the cause of onset and recurrence of disease is largely unknown with few studies identifying potential mechanisms of failed treatment. This study aimed to assess a panel of clinical samples from healthy women and those with RVVC to investigate the influence ofCandida, vaginal microbiome and antagonism betweenCandidaandLactobacilluson disease pathology. 16S rRNA sequencing characterised disease by a reduction in specific health-associatedLactobacillussuch asL. crispatus, coupled with an increase inL. iners.In vitroanalysis showedCandida albicansclinical isolates are capable of heterogeneous biofilm formation and show the presence of hyphae andC. albicansaggregates in vaginal lavage. Additionally, the ability ofLactobacillusto inhibitC. albicansbiofilm formation and biofilm-related gene expression was demonstrated. Using RNA sequencing technology, we were able to exploit a possible mechanism by whichL. crispatusmay aim to re-establish a healthy vaginal environment through amino-acid acquisition fromC. albicans. This study suggests RVVC is not entirely due to an arbitrary switch inC. albicansfrom commensal to pathogen and understanding interactions between the yeast and vaginalLactobacillusspecies may be more crucial to elucidating the cause of RVVC and developing appropriate therapies.
Direct-from-specimen microbial growth inhibition spectrums under antibiotic exposure and comparison to conventional antimicrobial susceptibility testing
Authors: Chen Jade , San Su Su Soe , Kung Amelia , Tomasek Michael , Liu Dakai , Rodgers William , Gau Vincent 
Published: February 2021

AbstractIncreasing global travel and changes in the environment may increase the frequency of contact with a natural host carrying an infection, and therefore increase our chances of encountering microorganisms previously unknown to humans. During an emergency (man-made, natural disaster, or pandemic), the etiology of infection might be unknown at the time of patient treatment. The existing local or global Antimicrobial Stewardship Programs might not be fully prepared for emerging/re-emerging infectious disease outbreaks, especially if they are caused by an unknown organism, engineered bioterrorist attack, or rapidly evolving superbug. We demonstrate an antimicrobial efficacy profiling method that can be performed in hours directly from clinical urine specimens. The antimicrobial potency is determined by the microbial growth inhibition and compared to conventional antimicrobial susceptibility testing (AST) results. The oligonucleotide probe pairs on the sensor were designed to target gram-negative bacteria, specificallyEnterobacteralesandPseudomonas aeruginosa. A total of 10 remnant clinical specimens from the CLIA labs of New York-Presbyterian Queens were tested, resulting in 100% categorical agreement with reference AST methods (Vitek and broth microdilution method). The combined categorical susceptibility reporting of 12 contrived urine specimens was 100% for ciprofloxacin, gentamicin, and meropenem over a range of microbial loads from 105to 108CFU/mL.
Promiscuous specialists: Host specificity patterns among generalist louse flies
Authors: Lehikoinen Aleksi , Pohjola Pekka , Valkama Jari , Mutanen Marko , Pohjoismäki Jaakko L.O. 
Published: February 2021

AbstractEctoparasites such as louse flies (Diptera: Hippoboscidae) have tendency for host specialization, which is driven by adaptation to host biology as well as competition avoidance between parasites of the same host. However, some louse fly species, especially in genera attacking birds, show wide range of suitable hosts. In the presented study, we have surveyed the current status of bird attacking louse flies in Finland to provide comprehensive host association data to analyse the ecological requirements of the generalist species. A thorough sampling of 9342 birds, representing 134 species, recovered 576 specimens of louse flies, belonging to six species:Crataerina hirundinis, C. pallida, Ornithomya avicularia, O. chloropus, O. fringillinaandOrnithophila metallica. Despite some overlapping hosts, the threeOrnithomyaspecies showed a notable pattern in their host preference, which was influenced not only by the host size but also by the habitat and host breeding strategy. We also provide DNA barcodes for most Finnish species of Hippoboscidae, which can be used as a resource for species identification as well as metabarcoding studies in the future.
Genome sequencing of the bacteriophage CL31 and interaction with the host strainCorynebacterium glutamicumATCC 13032
Authors: Hünnefeld Max , Viets Ulrike , Sharma Vikas , Wirtz Astrid , Hardy Aël , Frunzke Julia 
Published: February 2021

AbstractIn this study, we provide a comprehensive analysis of the genomic features of the phage CL31 and the infection dynamics with the biotechnologically relevant host strainCorynebacterium glutamicumATCC 13032. Genome sequencing and annotation of CL31 revealed a 45-kbp genome composed of 72 open reading frames, mimicking the GC content of its host strain (54.4 %). An ANI-based distance matrix showed the highest similarity of CL31 to the temperate corynephage Φ16. While theC. glutamicumATCC 13032 wild type strain showed only mild propagation of CL31, a strain lacking thecglIR-cglIIR-cglIMrestriction-modification system was efficiently infected by this phage. Interestingly, the prophage-free strainC. glutamicumMB001 featured an even accelerated amplification of CL31 compared to the Δresmodstrain suggesting a role of cryptic prophage elements in phage defense. Proteome analysis of purified phage particles and transcriptome analysis provide important insights into structural components of the phage and the response ofC. glutamicumto CL31 infection. Isolation and sequencing of CL31-resistant strains revealed SNPs in genes involved in mycolic acid biosynthesis suggesting a role of this cell envelope component in phage adsorption. Altogether, these results provide an important basis for further investigation of phage-host interactions in this important biotechnological model organism.