bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory-Dependent Model for the Dynamics of COVID-19 Pandemic
Authors: Furati K.M. , Sarumi I.O. , Khaliq A.Q.M. 
Published: June 2020

AbstractCOVID-19 pandemic has impacted people all across the world. As a result, there has been a collective effort to monitor, predict, and control the spread of this disease. Among this effort is the development of mathematical models that could capture accurately the available data and simulate closely the futuristic scenarios. In this paper, a fractional-order memory-dependent model for simulating the spread of COVID-19 is proposed. In this model, the impact of governmental action and public perception are incorporated as part of the time-varying transmission rate. The model simulation is performed using the two-step generalized exponential time-differencing method and tested for data from Wuhan, China. The mean-square errors demonstrate the merit of the fractional-order model and provide a good estimate of the optimal order.
Predictors of postoperative biochemical remission in acromegaly
Authors: Yao Shun , Chen Wen-Li , Tavakol Sherwin , Akter Farhana , Catalino Michael P. , luo Jie , Guo Xiao-Peng , Zeng Ai-Liang , Zekelman Leo , Mao Zhi-Gang , Zhu Yong-Hong , Wu Qing-Zhi , Laws Edward R , Bi Wenya Linda , Wang Hai-Jun 
Published: June 2020

ABSTRACTOBJECTIVEAcromegaly is a rare neuroendocrine condition that can lead to significant morbidity; therefore, large studies are invaluable for understanding the disease burden. Despite China’s vast population size, studies on acromegaly remain sparse. In this report, we aimed to investigate clinical characteristics and predictors of biochemical remission after surgery for acromegaly.METHODSA retrospective nationwide study was conducted using patient-reported data from the China Acromegaly Patient Association (CAPA) from 1998 to 2018. Univariate analyses were performed using Wilcoxon rank-sum tests, two-sample t-tests, and chi-squared tests. Using the purposeful selection method, multivariate logistic regression analysis was employed to determine independent predictors of biochemical remission at 3 months in patients after surgery.RESULTSOf the 575 cases (mean age: 37.3 years; 59% female), macroadenomas and invasive tumors (Knosp score 3-4) were 87% and 61%, respectively. Ninety-five percent of patients were treated first with surgery (5.1% transcranial and 94.9% endonasal) and 38.3% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 μg/L [odds ratio (OR)=0.61; 95% confidence interval (CI), 0.39-0.96; p=0.031], preoperative GH levels >28 μg/L (OR=0.56; 95% CI, 0.35-0.90; p=0.016), macroadenoma (OR=0.57; 95% CI, 0.33-0.97; p=0.041), giant adenomas (OR=0.17; 95% CI, 0.06-0.44; p=0.0005), Knosp score 3-4 (OR=0.39; 95% CI, 0.25-0.59; p<0.0001), and preoperative medication usage (OR=2.16; 95% CI, 1.38-3.39; p=0.0008).CONCLUSIONSIn this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.
A Streamlined CyTOF Workflow To Facilitate Standardized Multi-Site Immune Profiling of COVID-19 Patients
Authors: Geanon Daniel , Lee Brian , Kelly Geoffrey , Handler Diana , Upadhyaya Bhaskar , Leech John , Herbinet Manon , Valle Diane Del , Gnjatic Sacha , Kim-Schulze Seunghee , Merad Miriam , Rahman Adeeb H. 
Published: June 2020

AbstractMass cytometry (CyTOF) represents one of the most powerful tools in immune phenotyping, allowing high throughput quantification of over 40 single parameters at single-cell resolution. However, wide deployment of CyTOF-based immune phenotyping studies are limited by complex experimental workflows and the need for specialized CyTOF equipment and technical expertise. Furthermore, differences in cell isolation and enrichment protocols, antibody reagent preparation, sample staining and data acquisition protocols can all introduce technical variation that can potentially confound integrative analyses of large data-sets of samples processed across multiple labs.Here, we describe the validation of a streamlined whole blood CyTOF workflow that addresses many of these challenges and facilitates wider adoption of CyTOF immune monitoring across sites with limited technical expertise or sample-processing resources or equipment. Our workflow utilizes commercially available reagents including the Fluidigm MaxPar Direct Immune Profiling Assay, a dry tube 30-marker immunophenotyping panel, and SmartTube Proteomic Stabilizer, which allows for simple and reliable fixation and cryopreservation of whole blood samples. We validate a workflow that allows for streamlined staining of whole blood samples with minimal processing requirements or expertise at the site of sample collection, followed by shipment to a central CyTOF core facility for batched downstream processing and data acquisition. We further demonstrate the application of this workflow to characterize immune responses in a cohort of hospitalized COVID-19 patients, highlighting key disease-associated changes in immune cell frequency and phenotype.
Chronic exposure to TNF reprograms cell signaling pathways in fibroblast-like synoviocytes by establishing long-term inflammatory memory
Authors: Gangishetti Umesh , Ramirez-Perez Sergio , Jones Kyle , Arif Abul , Drissi Hicham , Bhattaram Pallavi 
Published: June 2020

ABSTRACTFibroblast-like synoviocytes (FLS) play a critical role in the pathogenesis of rheumatoid arthritis (RA). Chronic inflammation induces transcriptomic and epigenetic modifications that imparts a persistent catabolic phenotype to the FLS, despite their dissociation from the inflammatory environment. We analyzed high throughput gene expression and chromatin accessibility data from human and mouse FLS from our and other studies available on public repositories, with the goal of identifying the persistently reprogrammed signaling pathways driven by chronic inflammation. We found that the gene expression changes induced by short-term tumor necrosis factor-alpha (TNF) treatment were largely sustained in the FLS exposed to chronic inflammation. These changes that included both activation and repression of gene expression, were accompanied by the remodeling of chromatin accessibility. The sustained activated genes (SAGs) included established pro-inflammatory signaling components known to act at multiple levels of NF-kappaB, STAT and AP-1 signaling cascades. Interestingly, the sustained repressed genes (SRGs) included critical mediators and targets of the BMP signaling pathway. We thus identified sustained repression of BMP signaling as a unique constituent of the long-term inflammatory memory induced by chronic inflammation. We postulate that simultaneous targeting of these activated and repressed signaling pathways may be necessary to combat RA persistence.
In silico prediction of structure and function for a large family of transmembrane proteins that includes human Tmem41b
Authors: Mesdaghi Shahram , Murphy David L. , Rodríguez Filomeno Sánchez , Burgos-Mármol J. Javier , Rigden Daniel J. 
Published: June 2020

AbstractRecent strides in computational structural biology have opened up an opportunity to understand previously mysterious uncharacterised proteins. The under-representation of transmembrane proteins in the Protein Data Bank highlights the need to apply new and advanced bioinformatics methods to shed light on their structure and function. This study focuses on such a family; transmembrane proteins containing the Pfam domain PF09335 (‘SNARE_ASSOC’/‘VTT ‘/‘Tvp38’). One prominent member, Tmem41b, has been shown to be involved in early stages of autophagosome formation and is vital in mouse embryonic development. Here we use evolutionary covariance-derived information not only to construct and validateab initiomodels but also to make domain boundary predictions and infer local structural features. The results from the structural bioinformatics analysis of Tmem41b and its homologues show that they contain a tandem repeat that is clearly visible in evolutionary covariance data but much less so by sequence analysis. Furthermore, cross-referencing of other prediction data with the covariance analysis shows that the internal repeat features 2-fold rotational symmetry.Ab initiomodelling of Tmem41b reinforces these structural predictions. Local structural features predicted to be present in Tmem41b are also present in Cl−/H+antiporters. These results together strongly point to Tmem41b and its homologues as being transporters for an as-yet uncharacterised substrate and possibly using H+antiporter activity as its mechanism for transport.
A Role for Maternal Factors in Suppressing Cytoplasmic Incompatibility
Authors: Momtaz AJM Zehadee , Ahumada Sabagh Abraham D. , Amortegui Julian Gonzalez , Salazar Samuel A. , Finessi Andrea , Hernandez Jethel , Christensen Steen , Serbus Laura R. 
Published: June 2020

ABSTRACTWolbachiaare maternally transmitted bacterial endosymbionts, carried by approximately half of all insect species.Wolbachiaprevalence in nature stems from manipulation of host reproduction to favor the success of infected females. The best known reproductive modification induced byWolbachiais referred to as sperm-egg Cytoplasmic Incompatibility (CI). In CI, the sperm ofWolbachia-infected males cause embryonic lethality, attributed to paternal chromatin segregation defects during early mitotic divisions. Remarkably, the embryos ofWolbachia-infected females “rescue” CI lethality, yielding egg hatch rates equivalent to uninfected female crosses. Several models have been discussed as the basis for Rescue, but none have been demonstrated in robust CI models, which are genetically intractable. As such, the extent of host involvement in Rescue remains untested. In this study, we used a chemical feeding approach to assess maternal contributions to CI suppression inDrosophila simulans. We found that uninfected females exhibited significantly higher CI egg hatch rates in response to seven chemical treatments that affect DNA integrity, cell cycle control, and protein turnover. Three of these treatments suppressed CI induced by endogenouswRiWolbachia, as well as an ectopicwMelWolbachiainfection. When framed in terms of existing literature, the results implicate DNA integrity as a dynamic aspect of CI suppression for differentWolbachiastrains. The framework presented here, applied to diverse CI models, will further enrich our understanding of host reproductive manipulation by insect endosymbionts.
The N-terminus of GPR37L1 is proteolytically processed by matrix metalloproteases
Authors: Coleman James L. J. , Ngo Tony , Smythe Rhyll E. , Cleave Andrew J. , Jones Nicole M. , Graham Robert M. , Smith Nicola J. 
Published: June 2020

AbstractGPR37L1 is an orphan G protein-coupled receptor expressed exclusively in the brain and linked to seizures, neuroprotection and cardiovascular disease. Based upon the observation that fragments of the GPR37L1 N-terminus are found in human cerebrospinal fluid, we hypothesized that GPR37L1 was subject to post-translational modification. Heterologous expression of GPR37L1-eYFP in either HEK293 or U87 glioblastoma cells yielded two cell surface species of approximately equivalent abundance, the larger of which is N-glycosylated at Asn105. The smaller species is produced by matrix metalloprotease/ADAM-mediated proteolysis (shown by the use of pharmacological inhibitors) and has a molecular weight identical to that of a mutant lacking the entire N-terminus, Δ122 GPR37L1. Serial truncation of the N-terminus prevented GPR37L1 expression except when the entire N-terminus was removed, narrowing the predicted site of N-terminal proteolysis to residues 105-122. Using yeast expressing different G protein chimeras, we found that wild type GPR37L1, but not Δ122 GPR37L1, coupled constitutively to Gpa1/Gαs and Gpa1/Gα16 chimeras, in contrast to previous studies. We tested the peptides identified in cerebrospinal fluid as well as their putative newly-generated N-terminal ‘tethered’ counterparts in both wild type and Δ122 GPR37L1 Gpa1/Gαs strains but saw no effect, suggesting that GPR37L1 does not signal in a manner akin to the protease-activated receptor family. We also saw no evidence of receptor activation or regulation by the reported GPR37L1 ligand, prosaptide/TX14A. Finally, the proteolytically processed species predominated bothin vivoandex vivoin organotypic cerebellar slice preparations, suggesting that GPR37L1 is rapidly processed to a signaling-inactive form. Our data indicate that the function of GPR37L1in vivois tightly regulated by metalloprotease-dependent N-terminal cleavage.
Classification of grain amaranths using chromosome-level genome assembly of ramdana,A. hypochondriacus
Authors: Deb Saptarathi , J Suvratha , Ravi Samathmika , Rao K Raksha , Whadgar Saurabh , Hariharan Nivedita , Dixit Shubham , Sunil Meeta , Choudhary Bibha , Stevanato Piergiorgio , Ramireddy Eswarayya , Srinivasan Subhashini 
Published: June 2020

ABSTRACTIn the age of genomics-based crop improvement, a high-quality genome of a local landrace adapted to the local environmental conditions is critically important. Grain amaranths produce highly nutritional grains with a multitude of desirable properties including C4 photosynthesis highly sought-after in other crops. For improving the agronomic traits of grain amaranth and for the transfer of desirable traits to dicot crops, a reference genome of a local landrace is necessary. Towards this end, our lab had initiated sequencing the genome ofAmaranthus (A.) hypochondriacus(A.hyp_K_white) and had reported a draft genome in 2014. We selected this landrace because it is well adapted for cultivation in India during the last century and is currently a candidate for TILLING-based crop improvement. More recently, a high-quality chromosome-level assembly ofA. hypochondriacus(PI558499, Plainsman) was reported. Here, we report a chromosome-level assembly of A.hyp_K_white (AhKP) using low-coverage PacBio reads, contigs from the reported draft genome of A.hyp_K_white, raw HiC data and reference genome of Plainsman. The placement of A.hyp_K_white on the phylogenetic tree of grain amaranths of known accessions clearly suggests that A.hyp_K_white is genetically distal from Plainsman and is most closely related to the accessionPI619259from Nepal (Ramdana). Furthermore, the classification of another accession, Suvarna, adapted to the local environment and selected for yield and other desirable traits, is clearlyA. cruentus. A classification based on hundreds of thousands of SNPs validated taxonomy-based classification for a majority of the accessions providing the opportunity for reclassification of a few.
Folate and Tolazamide: Potential competitive inhibitors of barbiturate by in-silico molecular docking
Authors: Sharp Kumar 
Published: June 2020

AbstractBarbiturates are the first line drugs for treatment of epilepsy for adults and children in the developing world because of its low cost and proven effectiveness. Due to their adverse effects, no effective management of toxicity and difficulty in determining correct dosage, benzodiazepines are preferred over them. It is also used as a recreational drug, thereby contributing to cases of overdose. My present study was to find the inhibitors of barbiturates by in-silico molecular docking. This approach can highlight only competitive inhibitors as molecules in-silico are rigid and do not produce conformational changes in structure by allosteric binding. 450 FDA-approved drugs were docked to active site of barbiturate of Gleobacter ligand-gated ion channel (GLIC). Drug interactions were visualized, literature search was done to bring out the final results. Tolazamide, an oral anti-diabetic drug and 5-methyltetrahydrofolate, active metabolite of folic acid produced desired results. These results should be used clinically for validation.
Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions
Authors: Ke Zunlong , Oton Joaquin , Qu Kun , Cortese Mirko , Zila Vojtech , McKeane Lesley , Nakane Takanori , Zivanov Jasenko , Neufeldt Christopher J. , Lu John M. , Peukes Julia , Xiong Xiaoli , Kräusslich Hans-Georg , Scheres Sjors H.W. , Bartenschlager Ralf , Briggs John A.G. 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates the exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy. The structure and distribution of S on the virion surface, however, has not been characterised. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distributions of S trimers in situ on the virion surface. These results provide a basis for understanding the conformations of S present on the virion, and for studying their interactions with neutralizing antibodies.
First responders shape a prompt and sharp NF-κB–mediated transcriptional response to TNF-α
Authors: Zambrano Samuel , Loffreda Alessia , Carelli Elena , Stefanelli Giacomo , Colombo Federica , Bertrand Edouard , Tacchetti Carlo , Agresti Alessandra , Bianchi Marco E. , Molina Nacho , Mazza Davide 
Published: June 2020

SummaryNF-κB acts as the master regulator of the transcriptional response to inflammatory signals by translocating into the nucleus upon stimuli, but we lack a single-cell characterization of the resulting transcription dynamics. Here we show that transcription of NF-κB target genes is strongly heterogeneous in individual cells but dynamically coordinated at the population level, since the average nascent transcription is prompt (i.e. occurs almost immediately) and sharp (i.e. increases and decreases rapidly) compared to NF-κB nuclear localization. Using an NF-κB-controlled MS2 reporter we confirm that the population-level transcriptional activity emerges from a strongly heterogeneous response in single cells as compared to NF-κB translocation dynamics, including the presence of a fraction of “first responders”. Mathematical models show that a combination of NF-κB mediated gene activation and a gene activity module including a gene refractory state is enough to produce sharp and prompt transcriptional responses. Our data and models show how the expression of the target genes of a paradigmatic inducible transcription activator upon stimuli can be time-resolved at population level and yet heterogeneous across single cells.
Prognostic significance of Substance P/ Neurokinin 1 receptor and its association with hormonal receptors in breast carcinoma
Authors: Mehboob Riffat , Gilani Syed Amir , Hassan Amber , Tanvir Imrana , Khan Rizwan Ullah , Javaid Shaista , Akram Javed ,   Sadaf, Ahmad Fridoon Jawad , Munoz Miguel 
Published: June 2020

AbstractTo evaluate the expression and Immunolocalization of Substance P (SP)/ Neurokinin-1 Receptor (NK-1R) in Breast Carcinoma (BC) patients and it’s association with routine proliferative markers (ER, PR, HER2/ neu and Ki-67).MethodsA cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (Grade III), 8 of group B (Grade II) and only 3 cases of group C (Grade I). Age range comprised of patients from 20-80 years and the mean age of patients was 45.74 years. HE, ER, PR, HER2 and Ki-67 staining was performed as routine biomarkers. Samples were then processed for immunomarkers study of Substance P and NK-1R immunohistochemistry was performed for few cases.Results14/23 cases (61%) of group A, 7/8 cases (88%) of group B and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥ 10% tumors cells), labeled as “3+”, was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) case of group B. Moderate staining labelled as “2+” (in ≥ 10% tumor cells) was observed in 3/14 (21.4%) cases of group A, 4/8 (50%) cases of group B. weak positive staining “1+” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B and all 2/2 (100%) cases of group C.ConclusionsSP and NK-1R is overexpressed in breast carcinomas and there is significant association between grade of tumor and their overexpression. It may serve as a novel biomarker for grading of BC. We also suggest that NK-1R antagonists as a potential therapeutic strategy to inhibit and manage BC.Key PointsImmunohistochemical expression of Substance P and Neurokinin 1 Receptor in breast carcinoma tissue was evaluatedIt was strongly expressed in grade III, with maximum intensityIt may be investigated further for its role as prognostic and diagnostic markerTherapeutic potential of Neurokinin-1 Receptor antagonists must be explored
pixy: Unbiased estimation of nucleotide diversity and divergence in the presence of missing data
Authors: Korunes Katharine L , Samuk Kieran 
Published: June 2020

AbstractPopulation genetic analyses often use summary statistics to describe patterns of genetic variation and provide insight into evolutionary processes. Among the most fundamental of these summary statistics areπanddXY, which are used to describe genetic diversity within and between populations, respectively. Here, we address a widespread issue inπanddXYcalculation: systematic bias generated by missing data of various types. Many popular methods for calculatingπanddXYoperate on data encoded in the Variant Call Format (VCF), which condenses genetic data by omitting invariant sites. When calculatingπanddXYusing a VCF, it is often implicitly assumed that missing genotypes (including those at sites not represented in the VCF) are homozygous for the reference allele. Here, we show how this assumption can result in substantial downward bias in estimates ofπanddXYthat is directly proportional to the amount of missing data. We discuss the pervasive nature and importance of this problem in population genetics, and introduce a user-friendly UNIX command line utility,pixy, that solves this problem via an algorithm that generates unbiased estimates ofπanddXYin the face of missing data. We comparepixyto existing methods using both simulated and empirical data, and show thatpixyalone produces unbiased estimates ofπanddXYregardless of the form or amount of missing data. In sum, our software solves a long-standing problem in applied population genetics and highlights the importance of properly accounting for missing data in population genetic analyses.