bluuebunny/crossref_metadata_2025_split huggingface dataset:
Furry is required for cell movements during gastrulation and functionally interacts with NDR1
Authors: Cervino Ailen S. , Moretti Bruno , Stuckenholz Carsten , Grecco Hernán E. , Davidson Lance A. , Cirio M. Cecilia 
Published: May 2020

AbstractGastrulation is a key event in animal embryogenesis during which the germ layers precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation driving asymmetric cell division, cell movements and cell shape changes. Furry (Fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions mostly related to cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here we show that inXenopus, Fry participates in the regulation of morphogenetic processes during gastrulation. Using morpholino knock-down, we demonstrate a role of Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation, in addition to dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we demonstrate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.
HUMAN BREAST TUMOUR CELLS VIABILITY EFFECT OF AFRICAN DIOSCOREA ROTUNDATA TUBER EXTRACTS IN MCF-7 AND MDA-MB231 CELL LINES
Authors: Odimegwu Joy Ifunanya , Odukoya Olukemi Abiodun , Español Alejandro , Sales Maria Elena 
Published: May 2020

ABSTRACTObjectiveWe aim to test the efficacy of edibleDioscorea speciesgrown and consumed in Nigeria, Africa on two breast cancer cell lines; MCF-7 and MDA-MB231 derived from a luminal and a triple-negative breast cancer (TNBC) respectively and to confirm safety in non-tumour cells MCF-10A using a well established cytotoxic compound paclitaxel as a standard. Metastatic breast cancer is a prevalent cause of mortality in women around the world. Breast cancer therapies have greatly advanced in recent years, but many patients develop cancer re-occurrence and metastasis and subsequently yield to the disease because of chemoresistance.MethodsEthanolic extracts ofDioscorea rotundataboiled and raw (DiosB and DiosR) respectively were chemically analysed for the presence of diosgenin using HPLC and the cytotoxic activity of the extracts were tested on MCF-7, MDA-MB-231 and MCF-10A cellsIn vitroby MTT assay.ResultsDiosB and DiosR extracts showed a higher maximal effect on MCF-7 cells than on MDA-MB231 after 24 h and 48 h treatments (p<0.0001 and p<0.05 respectively). DiosR, if applied at a range between 50-70 g/ml, can be effective to reduce breast tumor cell viability without affecting non tumorigenic MCF-10A cells either at 24 h or at 48 h. DiosB showed an IC50of 38.83μg/ml while DiosR showed an IC50of 41.80μg/ml.ConclusionThese results show that ethanolic extracts ofDioscorea rotundatatubers could be used effectively to treat breast cancer tumors and this is in sync with its diosgenin content as otherDioscorea speciesapplied for similar treatments in Asia and elsewhere.
Song sparrows do not discriminate between their own song and stranger song
Authors: Akçay Çağlar , Beecher Michael D. 
Published: May 2020

AbstractBird song is socially learned. During song learning, the bird’s hearing its own vocalization is important for normal development of song. Whether bird’s own song is represented and recognized as a special category in adult birds, however, is unclear. If birds respond differently to their own songs when these are played back to them, this would be evidence for auditory self-recognition. To test this possibility, we presented song sparrow males (Melospiza melodia) playbacks of their own songs or stranger songs and measured aggressive responses as well as type matching. We find no evidence of behavioral discrimination of bird’s own song relative to the (non-matching) stranger song. These findings cast doubt on an earlier proposal that song sparrows display auditory self-recognition and support the common assumption in playback experiments that bird’s own song is perceived as stranger song.
Alterations in odor hedonics in the 5XFAD Alzheimer’s disease mouse model and the influence of sex
Authors: Roberts Elizabeth R. , Dossat Amanda M. , Mar Cortijo María del , Brundin Patrik , Wesson Daniel W. 
Published: May 2020

AbstractOlfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics are reported in the early stages of Alzheimer’s disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination – recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-months old 5XFAD (Tg6799) mice in the five-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD mice investigated odors longer than controls, an effect that was driven by 6-months old mice. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed towards individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences towards some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD mice. Taken together, 5XFAD mice, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations which may occur in AD mouse models, and how these are influenced by biological sex.
Extending the Martini coarse-grained forcefield to N-glycans
Authors: Shivgan Aishwary T. , Marzinek Jan K. , Huber Roland G. , Krah Alexander , Henchman Richard H. , Matsudaira Paul , Verma Chandra S. , Bond Peter J. 
Published: May 2020

AbstractGlycans play a vital role in a large number of cellular processes. Their complex and flexible nature hampers structure-function studies using experimental techniques. Molecular dynamics (MD) simulations can help in understanding dynamic aspects of glycans if the forcefield (FF) parameters used can reproduce key experimentally observed properties. Here, we present optimized coarse-grained (CG) Martini FF parameters for N-glycans, calibrated against experimentally derived binding affinities for lectins. The CG bonded parameters were obtained from atomistic (ATM) simulations for different glycan topologies including high mannose and complex glycans with various branching patterns. In the CG model, additional elastic networks are shown to improve maintenance of the overall conformational distribution. Solvation free energies and octanol-water partition coefficients were also calculated for various n-glycan disaccharide combinations. When using standard Martini non-bonded parameters, we observed that glycans spontaneously aggregated in the solution and required down-scaling of their interactions for reproduction of ATM model radial distribution functions. We also optimised the non-bonded interactions for glycans interacting with seven lectin candidates and show that scaling down the glycan-protein interactions can reproduce free energies obtained from experimental studies. These parameters should be of use in studying the role of glycans in various glycoproteins, carbohydrate binding proteins (CBPs) as well as their complexes, while benefiting from the efficiency of CG sampling.
Psychological morbidities and fatigue in patients with confirmed COVID-19 during disease outbreak: prevalence and associated biopsychosocial risk factors
Authors: Qi Rongfeng , Chen Wei , Liu Saiduo , Thompson Paul M. , Zhang Long Jiang , Xia Fei , Cheng Fang , Hong Ailing , Surento Wesley , Luo Song , Sun Zhi Yuan , Zhou Chang Sheng , Li Lingjiang , Jiang Xiangao , Lu Guang Ming 
Published: May 2020

AbstractObjectiveThe coronavirus disease 2019 (COVID-19) – a novel and highly infectious pneumonia – has now spread across China and beyond for over four months. However, its psychological impact on patients is unclear. We aim to examine the prevalence and associated risk factors for psychological morbidities and fatigue in patients with confirmed COVID-19 infection.MethodsAmidst the disease outbreak, 41 out of 105 COVID-19 patients in a local designated hospital in China were successfully assessed using a constellation of psychometric questionnaires to determine their psychological morbidities and fatigue. Several potential biopsychosocial risk factors (including pre-existing disabilities, CT severity score of pneumonia, social support, coping strategies) were assessed through multivariable logistic regression analyses to clarify their association with mental health in patients.Results43.9% of 41 patients presented with impaired general mental health, 12.2% had post-traumatic stress disorder (PTSD) symptoms, 26.8% had anxiety and/or depression symptoms, and 53.6% had fatigue. We did not find any association between pneumonia severity and psychological morbidities or fatigue in COVID-19 patients. However, high perceived stigmatization was associated with an increased risk of impaired general mental health and high perceived social support was associated with decreased risk. Besides, negative coping inclination was associated with an increased risk of PTSD symptoms; high perceived social support was associated with a decreased risk of anxiety and/or depression symptoms.ConclusionsPsychological morbidities and chronic fatigue are common among COVID-19 patients. Negative coping inclination and being stigmatized are primary risk factors while perceived social support is the main protective factor.
Early detection of severe COVID-19 disease patterns define near real-time personalised care, bioseverity in males, and decelerating mortality rates
Authors: Vizcaychipi Marcela P. , Shovlin Claire L , Hayes Michelle , Singh Suveer , Christie Linsey , Sisson Alice , Davies Roger , Lockie Christopher , Howard Alice , Brown Alexander , McCarthy Alex , Popescu Monica , Gupta Amandeep , Armstrong James , Said Hisham , Peters Timothy , Keays Richard T ,   ChelWest COVID-19 Consortium
Published: May 2020

ABSTRACTBackgroundCOVID-19 is a global health emergency. Recent data indicate a 50% mortality rate across UK intensive care units.MethodsA single institution, two-centre retrospective analysis following implementation of a Decision Support tool and real-time data dashboard for early detection of patients requiring personalised enhanced care, focussing on respiratory rate, diastolic blood pressure, oxygenation indices, C-reactive protein, D-dimer and ferritin. Protocols differing from conventional practice included high-dose prophylactic anticoagulation for all COVID-19 positive patients and prescription of antioxidants.ResultsBy 22/04/2020, 923 patients tested COVID-19 positive. 569 patients (61.7%) were male. The majority presented with advanced disease: interquartile ranges were C-reactive protein 44.9-179mg/L, D-dimer 1070-3802ng/mL, and ferritin 261-1208µg/L. Completed case fatality rates were 25.1% [95% CI 20.0, 30.0] in females, 40.5% [95% CI 35.9, 45.0] in males. 139 patients were admitted to intensive care where current death rates are 16.2% [95% CI 3.8, 28.7] in females, 38.2% [95% CI 28.6, 47.8] in males with no trends for differences based on ethnicity. A real-time traffic lights dashboard enabled rapid assessment of patients using critical parameters to accelerate adjustments to management protocols. In total 513 (55.6%) of patients were flagged as high risk for thromboembolic disease, exceeding the numbers flagged for respiratory deteriorations (N=391, 42.4%), or cytokine storm (N=68, 7.4%). There was minimal evidence that age was associated with disease severity, but males had higher levels of all dashboard indices, particularly C-reactive protein and ferritin (p<0.0001) which displayed no relationship with age.ConclusionsSurvival rates are encouraging. Protocols employed (traffic light-driven personalised care, protocolised early therapeutic anticoagulation based on D-dimer >1,000ng/mL and/or CRP>200 mg/L, personalised ventilatory strategies and antioxidants) are recommended to other units. Males are at greater risk of severe disease, most likely as the obligate SARS-CoV-2 receptor is encoded by the X-chromosome, and require especially close, and early attention.
Replicating extensive brain structural heterogeneity in individuals with schizophrenia and bipolar disorder
Authors: Wolfers Thomas , Rokicki Jaroslav , Alnæs Dag , Berthet Pierre , Agartz Ingrid , Kia Seyed Mostafa , Kaufmann Tobias , Zabihi Mariam , Moberget Torgeir , Melle Ingrid , Beckmann Christian F , Andreassen Ole A , Marquand Andre F , Westlye Lars T 
Published: May 2020

ABSTRACTIdentifying brain processes involved in the risk and development of mental disorders is a major aim. We recently reported substantial inter-individual heterogeneity in brain structural aberrations among patients with schizophrenia and bipolar disorder. Estimating the normative range of voxel-based morphometry (VBM) data among healthy individuals using a gaussian process regression (GPR) enables us to map individual deviations from the healthy range in unseen datasets. Here we aim to replicate our previous results in two independent samples of patients with schizophrenia (n1=94; n2=105), bipolar disorder (n1=116; n2=61) and healthy individuals (n1=400; n2=312). In line with previous findings with exception of the cerebellum our results revealed robust group level differences between patients and healthy individuals, yet only a small proportion of patients with schizophrenia or bipolar disorder exhibited extreme negative deviations from normality in the same brain regions. These direct replications support that group level-differences in brain structure disguise considerable individual differences in brain aberrations, with important implications for the interpretation and generalization of group-level brain imaging findings to the individual with a mental disorder.
Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips
Authors: Pichon Fabien , Busato Florence , Jochems Simon , Jacquelin Beatrice , Le Grand Roger , Deleuze Jean-Francois , Müller-Trutwin Michaela , Tost Jörg 
Published: May 2020

AbstractThe Infinium Human Methylation450 and Methylation EPIC BeadChips are useful tools for the study of the methylation state of hundreds of thousands of CpG across the human genome at affordable cost. However, in a wide range of experimental settings in particular for studies in infectious or brain-related diseases, human samples cannot be easily obtained. Hence, due to their close developmental, immunological and neurological proximity with humans, non-human primates are used in many research fields of human diseases and for preclinical research. Few studies have used DNA methylation microarrays in simian models. Microarrays designed for the analysis of DNA methylation patterns in the human genome could be useful given the genomic proximity between human and nonhuman primates. However, there is currently information lacking about the specificity and usability of each probe for many nonhuman primate species, including rhesus macaques (Macaca mulatta), originating from Asia, and African green monkeys originating from West-Africa (Chlorocebus sabaeus). Rhesus macaques and African green monkeys are among the major nonhuman primate models utilized in biomedical research. Here, we provide a precise evaluation and re-annotation of the probes of the two microarrays for the analysis of genome-wide DNA methylation patterns in these two Cercopithecidae species. We demonstrate that up to 162,000 of the 450K and 255,000 probes of the EPIC BeadChip can be reliably used inMacaca mulattaorChlorocebus sabaeus. The annotation files are provided in a format compatible with a variety of preprocessing, normalization and analytical pipelines designed for data analysis from 450K/EPIC arrays, facilitating high-throughput DNA methylation analyses inMacaca mulattaandChlorocebus sabaeus. They provide the opportunity to the research community to focus their analysis only on those probes identified as reliable. The described analytical workflow leaves the choice to the user to balance coverage versus specificity and can also be applied to other Cercopithecidae species.
Developmental chromatin programs determine oncogenic competence in melanoma
Authors: Baggiolini Arianna , Callahan Scott J. , Trieu Tuan , Tagore Mohita M. , Montal Emily , Weiss Joshua M. , Tischfield Sam E. , Fan Yujie , Campbell Nathaniel R. , Saurat Nathalie , Hollmann Travis , Simon-Vermot Theresa , Tickoo Satish K. , Taylor Barry S. , Koche Richard , Khurana Ekta , Studer Lorenz , White Richard M. 
Published: May 2020

AbstractOncogenes are only transforming in certain cellular contexts, a phenomenon called oncogenic competence. The mechanisms regulating this competence remain poorly understood. Here, using a combination of a novel human pluripotent stem cell (hPSC)-based cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600Edepends upon the intrinsic transcriptional program present in the cell of origin. Remarkably, in both systems, melanocytes (MC) are largely resistant to BRAF. In contrast, both neural crest (NC) and melanoblast (MB) populations are readily transformed. Molecular profiling reveals that NC/MB cells have markedly higher expression of chromatin modifying enzymes, and we discovered that the chromatin remodeler ATAD2 is required for response to BRAF and tumor initiation. ATAD2 forms a complex with SOX10, allowing for expression of downstream oncogenic programs. These data suggest that oncogenic competence is mediated by developmental regulation of chromatin factors, which then allow for proper response to those oncogenes.
Measuring context dependency in birdsong using artificial neural networks
Authors: Morita Takashi , Koda Hiroki , Okanoya Kazuo , Tachibana Ryosuke O. 
Published: May 2020

AbstractContext dependency is a key feature in sequential structures of human language, which requires reference between words far apart in the produced sequence. Assessing how long the past context has an effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper-bounded by methodological limitations. Here, we newly estimated the context dependency in birdsongs in a more scalable way using a modern neural-network-based language model whose accessible context length is sufficiently long. The detected context dependency was beyond the order of traditional Markovian models of birdsong, but was consistent with previous experimental investigations. We also studied the relation between the assumed/auto-detected vocabulary size of birdsong (i.e., fine-vs. coarse-grained syllable classifications) and the context dependency. It turned out that the larger vocabulary (or the more fine-grained classification) is assumed, the shorter context dependency is detected.
Functional requirement of theArabidopsisimportin-α nuclear transport receptor family in autoimmunity mediated by the NLR protein SNC1
Authors: Lüdke Daniel , Roth Charlotte , Kamrad Sieglinde A. , Messerschmidt Jana , Hartken Denise , Appel Jonas , Hörnich Bojan F. , Yan Qiqi , Kusch Stefan , Klenke Melanie , Gunkel Annette , Wirthmueller Lennart , Wiermer Marcel 
Published: May 2020

SUMMARYIMPORTIN-α3/MOS6 (MODIFIER OF SNC1, 6) is one of nine importin-α isoforms inArabidopsisthat recruit nuclear localization signal (NLS)-containing cargo proteins to the nuclear import machinery.IMP-α3/MOS6is required genetically for full autoimmunity of the nucleotide-binding leucine-rich repeat (NLR) immune receptor mutantsnc1(suppressor of npr1-1, constitutive 1) andMOS6also contributes to basal disease resistance. Here, we investigated the contribution of the otherimportin-α genes to both types of immune responses, and we analyzed potential interactions of all importin-α isoforms with SNC1. By using reverse-genetic analyses inArabidopsisand protein-protein interaction assays inN. benthamianawe provide evidence that among the nine α-importins inArabidopsis, IMP-α3/MOS6 is the main nuclear transport receptor of SNC1, and thatIMP-α3/MOS6is required selectively for autoimmunity ofsnc1and basal resistance to mildly virulentPseudomonas syringaeinArabidopsis.SIGNIFICANCE STATEMENTSpecific requirement for theArabidopsisα-importin MOS6 insnc1-mediated autoimmunity is explained by selective formation of MOS6-SNC1 nuclear import complexes.
Clinical Knowledge Graph Integrates Proteomics Data into Clinical Decision-Making
Authors: Santos Alberto , Colaço Ana R. , Nielsen Annelaura B. , Niu Lili , Geyer Philipp E. , Coscia Fabian , Albrechtsen Nicolai J Wewer , Mundt Filip , Jensen Lars Juhl , Mann Matthias 
Published: May 2020

SummaryThe promise of precision medicine is to deliver personalized treatment based on the unique physiology of each patient. This concept was fueled by the genomic revolution, but it is now evident that integrating other types of omics data, like proteomics, into the clinical decision-making process will be essential to accomplish precision medicine goals. However, quantity and diversity of biomedical data, and the spread of clinically relevant knowledge across myriad biomedical databases and publications makes this exceptionally difficult. To address this, we developed the Clinical Knowledge Graph (CKG), an open source platform currently comprised of more than 16 million nodes and 220 million relationships to represent relevant experimental data, public databases and the literature. The CKG also incorporates the latest statistical and machine learning algorithms, drastically accelerating analysis and interpretation of typical proteomics workflows. We use several biomarker studies to illustrate how the CKG may support, enrich and accelerate clinical decision-making.Graphical Abstract
Bioengineered ciprofloxacin loaded chitosan nanoparticles for the treatment of Bovine Mastitis
Authors: Yadav Preeti , Gaur Preksha , Yadav Awadh B. , Huma Z. I. , Sharma Neelesh 
Published: May 2020

AbstractMastitis is the most devastating economic disease of dairy cattle. Mastitis in dairy cattle frequently occurs during the dry period or in early lactation. E. coli. andS. aureusis the main causative agent of mastitis. S. aureushas an ability to form encapsulated focuses in the udder and develop subclinical form of mastitis. This property of bacteria hinders the effective cure during lactation period. Antibiotics used for treatments have a short half-life span at the site of action because of frequent milking, therefore unable to maintain desired drug concentration for effective clearance of bacteria. We demonstrated the potential of ciprofloxacin encapsulated nanocarriers which can improve availability of drugs and could provide effective means of the treatment of mastitis. These drug loaded nanoparticles show low toxicity & slow clearance from the site of action. Antimicrobial studied against clinical strain ofE.coli.andStaphylococcus aureuszone of inhibition depend on dose 0.5 mg to 2 mg/ml nanoparticles solution from 11.6 to 14.5 mm and 15 to 18mm. These nanoparticles show good antimicrobial activity in broth culture as well against bacteria.