bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocyte-secreted chordin-like 1 regulates spine density after ischemic stroke
Authors: Blanco-Suarez Elena , Allen Nicola J 
Published: December 2020

AbstractIschemic stroke occurs when the brain is deprived of blood flow, preventing cells from receiving nutrients necessary to perform basic vital functions. In the peri-infarct area neurons undergo an acute loss of dendritic spines along with morphological alterations, which ultimately modify synaptic plasticity and determine neuronal survival. Astrocytes have been shown to play protective or detrimental roles in neuronal survival post-stroke, depending on the specific stage, yet we lack a clear understanding of the underlying mechanisms triggered at these different time points. Recently chordin-like 1 (Chrdl1) was identified as an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse visual cortex, leading us to ask if Chrdl1 regulates spine density and recovery from stroke. Using photothrombosis to model ischemic stroke, we studied Chrdl1 KO mice during the acute and subacute phases post-stroke (1 and 7 days after injury, respectively) to assess the potential of Chrdl1 to regulate spine density, glial reactivity and injury volume, characteristics that are involved in functional recovery after ischemia. We find that the absence of Chrdl1 prevents ischemia-induced spine loss in the peri-infarct area, a feature that indicates an important role of astrocytes in recovery from ischemic stroke.
Myogenetic oligodeoxynucleotide (myoDN) complexed with berberine promotes differentiation of chicken skeletal muscle myoblasts
Authors: Nihashi Yuma , Shinji Sayaka , Umezawa Koji , Shimosato Takeshi , Ono Tamao , Kagami Hiroshi , Takaya Tomohide 
Published: December 2020

AbstractSkeletal muscle myoblasts are myogenic precursors that develop into myofibers during muscle formation. Improvement of myoblast differentiation is important for advancing meat production by domestic animals. We recently identified novel oligodeoxynucleotides (ODNs) termed myogenetic ODNs (myoDNs) that promote the differentiation of mammalian myoblasts. An isoquinoline alkaloid, berberine, forms a complex with one of the myoDNs, iSN04, and enhances its activities. This study investigated the effects of myoDNs on chicken myoblasts to elucidate their species-specific actions. Seven myoDNs (iSN01-iSN07) were found to facilitate the differentiation of chicken myoblasts into myosin heavy chain (MHC)-positive myocytes. The iSN04-berberine complex exhibited a higher myogenetic activity than iSN04 alone, which was shown to enhance the differentiation of myoblasts into myocytes, myotube formation, and myogenic gene expression (MyoD, myogenin, MHC, and myomaker). These data indicate that myoDNs promoting chicken myoblast differentiation may be used as potential feed additives in broiler diets.
Development and external validation of a logistic regression derived formula based on repeated routine hematological measurements predicting survival of hospitalized Covid-19 patients
Authors: Heber Stefan , Pereyra David , Schrottmaier Waltraud C. , Kammerer Kerstin , Santol Jonas , Pawelka Erich , Hana Markus , Scholz Alexander , Liu Markus , Hell Agnes , Heiplik Klara , Lickefett Benno , Havervall Sebastian , Traugott Marianna T. , Neuböck Matthias , Schörgenhofer Christian , Seitz Tamara , Firbas Christa , Karolyi Mario , Weiss Günter , Jilma Bernd , Thålin Charlotte , Bellmann-Weiler Rosa , Salzer Helmut J.F. , Fischer Michael J.M. , Zoufaly Alexander , Assinger Alice 
Published: December 2020

AbstractBackgroundThe Covid-19 pandemic has become a global public health crisis and providing optimal patient care while preventing a collapse of the health care system is a principal objective worldwide.ObjectiveTo develop and validate a prognostic model based on routine hematological parameters to predict uncomplicated disease progression to support the decision for an earlier discharge.DesignDevelopment and refinement of a multivariable logistic regression model with subsequent external validation. The time course of several hematological variables until four days after admission were used as predictors. Variables were first selected based on subject matter knowledge; their number was further reduced using likelihood ratio-based backward elimination in random bootstrap samples.SettingModel development based on three Austrian hospitals, validation cohorts from two Austrian and one Swedish hospital.ParticipantsModel development based on 363 survivors and 78 non-survivors of Covid-19 hospitalized in Austria. External validation based on 492 survivors and 61 non-survivors hospitalized in Austria and Sweden.OutcomeIn-hospital death.Main ResultsThe final model includes age, fever upon admission, parameters derived from C-reactive protein (CRP) concentration, platelet count and creatinine concentration, approximating their baseline values (CRP, creatinine) and change over time (CRP, platelet count). In Austrian validation cohorts both discrimination and calibration of this model were good, with c indices of 0.93 (95% CI 0.90 - 0.96) in a cohort from Vienna and 0.93 (0.88 - 0.98) in one from Linz. The model performance seems independent of how long symptoms persisted before admission. In a small Swedish validation cohort, the model performance was poorer (p = 0.008) compared with Austrian cohorts with a c index of 0.77 (0.67 - 0.88), potentially due to substantial differences in patient demographics and clinical routine.ConclusionsHere we describe a formula, requiring only variables routinely acquired in hospitals, which allows to estimate death probabilities of hospitalized patients with Covid-19. The model could be used as a decision support for earlier discharge of low-risk patients to reduce the burden on the health care system. The model could further be used to monitor whether patients should be admitted to hospital in countries with health care systems with emphasis on outpatient care (e.g. Sweden).
In vitro measurements of protein–protein interactions show that antibody affinity governs the inhibition of SARS-CoV-2 spike/ACE2 binding in convalescent serum
Authors: Fiedler Sebastian , Piziorska Monika A. , Denninger Viola , Morgunov Alexey S. , Ilsley Alison , Malik Anisa Y. , Schneider Matthias M. , Devenish Sean R. A. , Meisl Georg , Aguzzi Adriano , Fiegler Heike , Knowles Tuomas P. J. 
Published: December 2020

AbstractThe humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2–spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the binding energies of the binary interactions between the ACE2 receptor and the spike protein, and the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential areas of application ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.
Mutation Landscape of SARS COV2 in Africa
Authors: Nassir Angus A. , Musanabaganwa Clarisse , Mwikarago Ivan 
Published: December 2020

ABSTRACTCOVID-19 disease has had a relatively less severe impact in Africa. To understand the role of SARS CoV2 mutations on COVID-19 disease in Africa, we analysed 282 complete nucleotide sequences from African isolates deposited in the NCBI Virus Database. Sequences were aligned against the prototype Wuhan sequence (GenBank accession:NC_045512.2) in BWA v. 0.7.17. SAM and BAM files were created, sorted and indexed in SAMtools v. 1.10 and marked for duplicates using Picard v. 2.23.4. Variants were called with mpileup in BCFtools v. 1.11. Phylograms were created using Mr. Bayes v 3.2.6. A total of 2,349 single nucleotide polymorphism (SNP) profiles across 294 sites were identified. Clades associated with severe disease in the United States, France, Italy, and Brazil had low frequencies in Africa (L84S=2.5%, L3606F=1.4%, L3606F/V378I/=0.35, G251V=2%). Sub Saharan Africa (SSA) accounted for only 3% of P323L and 4% of Q57H mutations in Africa. Comparatively low infections in SSA were attributed to the low frequency of the D614G clade in earlier samples (25% vs 67% global). Higher disease burden occurred in countries with higher D614G frequencies (Egypt=98%, Morocco=90%, Tunisia=52%, South Africa) with D614G as the first confirmed case. V367F, D364Y, V483A and G476S mutations associated with efficient ACE2 receptor binding and severe disease were not observed in Africa. 95% of all RdRp mutations were deaminations leading to CpG depletion and possible attenuation of virulence. More genomic and experimental studies are needed to increase our understanding of the temporal evolution of the virus in Africa, clarify our findings, and reveal hot spots that may undermine successful therapeutic and vaccine interventions.
Patch characteristics and domestic dogs differentially affect carnivore space use in fragmented landscapes in Southern Chile
Authors: Malhotra Rumaan , Jiménez Jaime E. , Harris Nyeema C. 
Published: December 2020

AbstractIn an increasingly anthropogenic world, native species face multiple interacting threats. Habitat fragmentation and domestic dogs are two such perturbations threatening terrestrial mammals globally. Here, we implemented a camera trap survey in the fragmented central valley/Andean foothills transition of the Los Lagos Region in Southern Chile to evaluate space use of native carnivores in a landscape comprised of patches of native forest amidst a matrix of pastureland. Using an occupancy modeling framework to account for imperfect detection, we examined the impacts of dogs and landscape metrics of fragmentation on three mesocarnivores – the foxes culpeo (Lycalopex culpaeus) and chilla (Lycalopex griseus) and the wild cat güiña (Leopardus guigna). Factors driving occupancy differed for each of the native species, while detection rates for both canid species increased with dog occupancy. We found that a small (12%) simulated increase in dog occupancy negatively impacted the spatial use of the culpeo. Habitat loss and fragmentation were positive drivers for the chilla and the dog, and indirectly impacted the culpeo through the domestic dog. The güiña did not respond to fragmentation and other habitat covariates or dog occupancy. Instead, all native carnivore species temporally partitioned diel activity with dogs. We highlight that the effects of dogs or fragmentation are not ubiquitous across the carnivore guild with varied tolerance. However, future conditions of increased fragmentation and habitat loss will likely increase the potential contact between domestic dogs and native carnivores.
Calibrating Hall-Effect valvometers accounting for electromagnetic properties of the sensor and dynamic geometry of the bivalves shell
Authors: Guarini Jean-Marc , Coston-Guarini Jennifer , Comeau Luc A. 
Published: December 2020

AbstractHall-Effect valvometry (HES) is being used to describe bivalve valve gape variations and infer environmental perturbations in a variety of aquatic environments. Surprisingly, the published calibrations in ecological literature ignore both the electromagnetic properties of HES and that the valves rotate around their hinge when they move. The high sensitivity of HES suggests these features should be accounted for explicitly to estimate measurement accurately. To address these issues, two calibration functions were developed based on the electromagnetic properties of the HES: one assumes that the HES and magnet are maintained on the same linear axis, and the second model accounts for the geometric properties of the system (i.e. variations of the angle between HES and the magnet during shell rotation). The great scallop (Pecten maximus) was used as biological model because of its large range of valve openings. HES were installed on the flat valve and magnets installed on the opposing rounded valve; 12 individuals of similar size (10 ± 1(SD) cm), were equipped and placed in controlled experimental conditions. A calibration was done for each individual once time series recordings were completed. The variability of parameter estimates was calculated with a bootstrap method. The second model (with rotatation) improves valve gape distance estimates for larger openings despite the decrease of sensor sensitivity. To infer valve gape dynamics, the reciprocal calculation of the calibration function was formalized and applied to the Hall voltage time series. Our analysis suggests that under controlled laboratory conditions, scallops are partially open most of the time (inter-valve distance equalca. 27 mm on average, or 45 % of the average maximum opening distance). Interspersed in this continuous regime, individual scallops performed closing events at a frequency ofca. 2.5 closings per hour. A closing event is a movement that is fast enough relative to the recording frequency (10 Hz) to qualify as discrete. We find that the inversed calibration model without rotation allows negative value estimates, which indicates that this calibration function is incorrect. In contrast, the inversed calibration model with valve rotation around the hinge constrains gape distance values in their domain of definition which automatically excludes sensor readings that produce negative values from estimated gape time series.
Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus
Authors: Salisbury Aaron J. , Blackwood Christopher A. , Cadet Jean Lud 
Published: December 2020

AbstractPeople suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression ofGluA1-3 and GluN2a-csubunits as well asGrm3,Grm5,Grm6andGrm8subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes inGluA1-3, Grm6, and Grm8mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.
Information Retrieval using Machine Learning for Biomarker Curation in the Exposome-Explorer
Authors: Lamurias Andre , Jesus Sofia , Neveu Vanessa , Salek Reza M , Couto Francisco M 
Published: December 2020

AbstractIn 2016, the International Agency for Research on Cancer, part of the World Health Organization, released the Exposome-Explorer, the first database dedicated to biomarkers of exposure for environmental risk factors for diseases. The database contents resulted from a manual literature search that yielded over 8500 citations, but only a small fraction of these publications were used in the final database. Manually curating a database is time-consuming and requires domain expertise to gather relevant data scattered throughout millions of articles. This work proposes a supervised machine learning approach to assist the previous manual literature retrieval process.The manually retrieved corpus of scientific publications used in the Exposome-Explorer was used as training and testing sets for the machine learning models (classifiers). Several parameters and algorithms were evaluated to predict an article’s relevance based on different datasets made of titles, abstracts and metadata.The top performance classifier was built with the Logistic Regression algorithm using the title and abstract set, achieving an F2-score of 70.1%. Furthermore, from 705 articles classified as relevant, we extracted 545 biomarkers, including 460 new candidate entries to the Exposome-Explorer database.Our methodology reduced the number of articles to be manually screened by the database curators by nearly 90%, while only misclassifying 22.1% of the relevant articles. We expect that this methodology can also be applied to similar biomarkers datasets or be adapted to assist the manual curation process of similar chemical or disease databases.
Structures of the human mitochondrial ribosome recycling complexes reveal distinct mechanisms of recycling and antibiotic resistance
Authors: Koripella Ravi Kiran , Deep Ayush , Agrawal Ekansh K. , Keshavan Pooja , Banavali Nilesh K. , Agrawal Rajendra K. 
Published: December 2020

AbstractRibosomes are recycled for a new round of translation initiation by dissociation of ribosomal subunits, messenger RNA and transfer RNA from their translational post-termination complex. Mitochondrial ribosome recycling factor (RRFmt) and a recycling-specific homolog of elongation factor G (EF-G2mt) are two proteins with mitochondria-specific additional sequences that catalyze the recycling step in human mitochondria. We have determined high-resolution cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) in complex with RRFmt, and the mitoribosomal large 39S subunit in complex with both RRFmtand EF-G2mt. In addition, we have captured the structure of a short-lived intermediate state of the 55S•RRFmt•EF-G2mtcomplex. These structures clarify the role of a mitochondria-specific segment of RRFmtin mitoribosome recycling, identify the structural distinctions between the two isoforms of EF-Gmtthat confer their functional specificity, capture recycling-specific conformational changes in the L7/L12 stalk-base region, and suggest a distinct mechanistic sequence of events in mitoribosome recycling. Furthermore, biochemical and structural assessments of the sensitivity of EF-G2mtto the antibiotic fusidic acid reveals that the molecular mechanism of antibiotic resistance for EF-G2mtis markedly different from that exhibited by mitochondrial elongation factor EF-G1mt, suggesting that these two homologous mitochondrial proteins have evolved diversely to negate the effect of a bacterial antibiotics.
Dissecting the midlife crisis: Disentangling social, personality and demographic determinants in social brain anatomy
Authors: Kiesow Hannah , Uddin Lucina Q. , Bernhardt Boris C. , Kable Joseph , Bzdok Danilo 
Published: December 2020

AbstractIn any stage of life, humans crave social connection with other people. In midlife, transitions in social networks can be related to new leadership roles at work or becoming a caregiver for aging parents. Previous neuroimaging studies have reported that during midlife, especially the medial prefrontal cortex (mPFC) undergoes structural remodeling changes. Social behavior, personality predisposition, and demographic profile all bear intimate relation with the mPFC according to separate literature streams. To integrate these three areas commonly studied in isolation, we explicitly modeled their unique links with brain structure using a fully probabilistic framework. We weighed against each other a rich collection of 40 traits with their interindividual variation in social brain morphology in ~10,000 middle-aged UK Biobank participants (40-69 years at recruitment). Across conducted analyses, household size and daily routine schedules showed several of the largest effects in explaining variation in social brain regions. We revealed male-biased effects in the dorsal mPFC and amygdala for job income, and a female-biased effect in the ventral mPFC for health satisfaction. Our population investigation offers a more complete perspective into how adults at the midlife milestone may navigate life depending on their identity and status.
High-resolution Cell Atlas of Domestic Pig Lung and Online Platform Exploring for Lung Single Cell
Authors: Zhang Lijing , Zhu Jiacheng , Wang Haoyu , Xia Jun , Liu Ping , Chen Fang , Jiang Hui , Wu Weiying , Luo Lihua , Chen Dongsheng , Zhang Xingliang 
Published: December 2020

AbstractDue to the comparable organ sizes and physiology to human beings, genetically engineered pig is gradually regarded as an optimal source of human for transplantation and an excellent model for human diseases research. The major barrier between pig and human is mainly cellular heterogeneity and immune incompatibilities. Myriad scRNA-seq data of human has been reported, but the counterpart in pig is scarce. Here, we applied scRNA-seq technology to study the cellular heterogeneity of 3 months old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on this data, we systematically characterized transcription factor regulatory networks, cell-cell communications in each cell type, and comparison of them and those in human lung. We first presented a comprehensive and openly accessible online platform, ScdbLung, which was composed of three functional modules (Marker, Cluster, and Download) and dedicated to exploiting the valuable resources of lung scRNA-seq data across four mammalian species. Overall, our scRNA-seq atlas of domestic pig lung, conserved transcription factor regulatory networks and cell-cell communications between domestic pig and human, and ScdbLung could provide guidance for porcine lung research and clinical applicability.