bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a unique TCR repertoire, consistent with a superantigen selection process in Children with Multi-system Inflammatory Syndrome
Authors: Porritt Rebecca A , Paschold Lisa , Rivas Magali Noval , Cheng Mary Hongying , Yonker Lael M , Chandnani Harsha , Lopez Merrick , Simnica Donjete , Schultheiß Christoph , Santiskulvong Chintda , Van Eyk Jennifer , Fasano Alessio , Bahar Ivet , Binder Mascha , Arditi Moshe 
Published: November 2020

SummaryMultisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares many clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. The superantigen specificity for binding different Vβ-chains results in Vβ-skewing, whereby T cells with specific Vβ-chains and diverse antigen specificity are overrepresented in the TCR repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCR Beta Variable gene (TRBV)11-2. Furthermore, TRBV11-2 skewing was remarkably correlated with MIS-C severity and serum cytokine levels. Further analysis of TRBJ gene usage and CDR3 length distribution of MIS-C expanding TRBV11-2 clones revealed extensive junctional diversity, indicating a superantigen-mediated selection process for TRBV expansion.In silicomodelling indicates that polyacidic residues in TCR Vβ11-2 engage in strong interactions with the superantigen-like motif of SARS-CoV-2 spike glycoprotein. Overall, our data indicate that the immune response in MIS-C is consistent with superantigenic activation.HighlightsMultisystem Inflammatory Disease in Children (MIS-C) patients exhibit T cell receptor (TCR) repertoire skewing, with expansion of T cell Receptor Beta Variable gene (TRBV)11-2TRBV11-2 skewing correlates with MIS-C severity and cytokine stormJ gene/CDR3 diversity in MIS-C patients is compatible with a superantigen selection processIn silicomodelling indicates TCR Vβ11-2 engages in CDR3-independent interactions with the polybasic insert P681RRAR in the SAg-like motif of SARS-CoV-2 spike
Proteolysis-free cell migration through crowded environments via mechanical worrying
Authors: Driscoll Meghan K. , Welf Erik S. , Weems Andrew , Sapoznik Etai , Zhou Felix , Murali Vasanth S. , Garcia-Arcos Juan Manuel , Roh-Johnson Minna , Piel Matthieu , Dean Kevin M. , Fiolka Reto , Danuser Gaudenz 
Published: November 2020

AbstractMigratory cells often encounter crowded microenvironments through which they must find or make a path. Amoeboid cells are thought to find a path by deforming their bodies to squeeze through tight spaces. Yet many amoeboid cells seem to maintain a near spherical morphology as they move. To examine this unexplored mechanism of migration, we visualized amoeboid melanoma cells in dense environments and found that they carve a path via bleb-driven mechanical degradation of extracellular matrix components without proteolytic degradation. Interactions between adhesions and collagen at the cell front induce a signaling cascade that promotes bleb enlargement via branched actin polymerization. Large blebs abrade collagen, creating feedback between extracellular matrix structure, cell morphology and polarization that enables both path generation and persistent movement.
TRPM2 promotes pancreatic cancer by PKC/MAPK pathway
Authors: Lin Rui , Bao Xunxia , Wang Hui , Zhu Sibo , Liu Zhongyan , Chen Quanning , Ai Kaixing , Shi Baomin 
Published: November 2020

AbstractBackgroundThe mechanism of pancreatic cancer(PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. This study was designed to investigate the role and mechanism of TRPM2 in pancreatic cancer.MethodsTRPM2 overexpressed and siRNA plasmid were created and transfected with pancreatic cancer cell line(BxPC-3) to construct the cell model. We employed CCK-8, Transwell, scratch wound, and nude mice tumor bearing model to investigate the role of TRPM2 in pancreatic cancer. Besides, we collected the clinical data, tumor tissue sample(TT) and para-tumor sample(TP) from the pancreatic cancer patients treated in our hospital. We analyzed the mechanism of TRPM2 in pancreatic cancer by transcriptome analysis, Westernblot, and PCR.ResultsOverexpressed TRPM2 could promote pancreatic cancer in proliferation, migration, and invasion ability in no matter the cell model or nude mice tumor bearing model. TRPM2 level is highly negative correlated to the overall survival and progression-free survival time in PA patients, however, it is significantly increased in PA tissue as the tumor stage increases. The transcriptome analysis, GSEA analysis, Westernblot, and PCR results indicates TRPM2 is highly correlated with PKC/MAPK pathways.ConclusionTRPM2 could directly activate PKCα by calcium or indirectly activate PKCε and PKCδ by increased DAG in PC, which promote PC by downstream MAPK/MEK pathway activation.
Full species-wide leaf and seed ionomic diversity ofArabidopsis thaliana
Authors: Campos Ana Carolina A. L. , van Dijk William F.A. , Ramakrishna Priya , Giles Tom , Korte Pamela , Douglas Alex , Smith Pete , Salt David E. 
Published: November 2020

SummarySoil is a heterogenous reservoir of essential elements needed for plant growth and development. Plants have evolved mechanisms to balance their nutritional needs based on availability of nutrients. This has led to genetically-based variation in the elemental composition ‘ionome’, of plants, both within and between species.We explore this natural variation using a panel of wild-collected, geographically widespreadArabidopsis thalianaaccessions from the 1001 Genomes Project including over 1,135 accessions, and the 19 parental accessions of the Multi-parent Advanced Generation Inter-Cross (MAGIC) panel, all with full-genome sequences available.We present an experimental design pipeline for high-throughput ionomic screenings and analyses with improved normalisation procedures to account for errors and variability in conditions often encountered in large-scale, high-throughput data collection. We report quantification of the complete leaf and seed ionome of the entire collection using this pipeline and a digital tool-IonExplorer to interact with the dataset.We describe the pattern of natural ionomic variation across theA. thalianaspecies and identify several accessions with extreme ionomic profiles. It forms a valuable resource for exploratory QTL, GWA studies to identify genes underlying natural variation in leaf and seed ionome and genetic adaptation of plants to soil conditions.
Multimodal single-cell chromatin analysis with Signac
Authors: Stuart Tim , Srivastava Avi , Lareau Caleb , Satija Rahul 
Published: November 2020

The recent development of experimental methods for measuring chromatin state at single-cell resolution has created a need for computational tools capable of analyzing these datasets. Here we developed Signac, a framework for the analysis of single-cell chromatin data, as an extension of the Seurat R toolkit for single-cell multimodal analysis. Signac enables an end-to-end analysis of single-cell chromatin data, including peak calling, quantification, quality control, dimension reduction, clustering, integration with single-cell gene expression datasets, DNA motif analysis, and interactive visualization. Furthermore, Signac facilitates the analysis of multimodal single-cell chromatin data, including datasets that co-assay DNA accessibility with gene expression, protein abundance, and mitochondrial genotype. We demonstrate scaling of the Signac framework to datasets containing over 700,000 cells.AvailabilityInstallation instructions, documentation, and tutorials are available at:https://satijalab.org/signac/
Top-down acetylcholine contributes to social discrimination via enabling action potentials in olfactory bulb vasopressin cells
Authors: Suyama Hajime , Egger Veronica , Lukas Michael 
Published: November 2020

AbstractSocial discrimination in rats requires activation of the intrinsic bulbar vasopressin system, but it is unclear how this system comes into operation, as olfactory nerve stimulation primarily inhibits bulbar vasopressin cells (VPCs). Here we show that stimulation with a conspecific can activate bulbar VPCs, indicating that VPC activation depends on more than olfactory cues during social interaction. A series ofin-vitroelectrophysiology, pharmacology and immunohistochemistry experiments implies that acetylcholine probably originating from centrifugal projections can enable olfactory nerve-evoked action potentials in VPCs. Finally, cholinergic activation of the vasopressin system contributes to vasopressin-dependent social discrimination, since recognition of a known rat was blocked by bulbar infusion of the muscarinic acetylcholine receptor antagonist atropine and rescued by additional bulbar application of vasopressin. Thus, we demonstrated that top-down cholinergic modulation of bulbar VPC activity is involved in social discrimination in rats.
Geometric effects of volume-to-surface mapping of fMRI data
Authors: Ciantar Keith George , Farrugia Christine , Scerri Kenneth , Xu Ting , Bajada Claude J. 
Published: November 2020

AbstractIn this work, we identify a problem with the process of volume-to-surface mapping of functional Magnetic Resonance Imaging (fMRI) data when interested in investigating local connectivity. We show that neighborhood correlations on the surface of the brain vary spatially with anatomical patterns (gyral structure), even when the underlying volumetric data are uncorrelated noise. This could potentially have impacted studies focusing upon local neighborhood connectivity. We explore the effects of this anomaly across varying data resolutions and surface mesh densities, and propose an approach to mitigate these unwanted effects.
Serotonin transporter knockout in rats modulates category learning
Authors: Guo Chao Ciu-Gwok , Minda John Paul , Homberg Judith 
Published: November 2020

AbstractLower function of the serotonin transporter (5-HTT) has a strong relationship with the development of autism spectrum disorder (ASD) in humans. One characteristic of ASD is the repetitive and restrictive behavior, which may form the basis for better memory and savant skills in some people with ASD. This characteristic in ASD may reflect a tendency towards an exploitation strategy rather than an exploration strategy during learning. Using a rat model, we developed a touchscreen-based task for testing 5-HTT knockout effects on stimulus category learning. By analyzing the data with a reinforcement learning drift diffusion model, we find that 5-HTT knockout rats show a lower learning rate and apply more of an exploitation versus exploration strategy compared to WT rats during category learning. The decision bound of decision-making during stimulus generalization indicates that more 5-HTT knockout rats than WT rats exploit irrelevant information to categorize stimuli. The touchscreen-based task we developed greatly increases the translational value from animals to humans and helps to understand the behavioral mechanisms underlying repetitive behavior in ASD.
Changes in nitrogen pools in the maize-soil system after urea or straw application to a typical intensive agricultural soil: A15N tracer study
Authors: Zhang Jie , He Ping , Wei Dan , Jin Liang , Zhang Lijuan , Li Ling , Zhao Shicheng , Xu Xinpeng , Zhou Wei , Christie Peter , Qiu Shaojun 
Published: November 2020

AbstractA15N maize pot experiment was conducted to compare the N value of fertilizer alone and fertilizer combined with straw at an equivalent N rate. The four treatments were control (CK),15N-urea,15N-urea plus straw, and15N-straw plus urea. Soil N pools, maize N and their15N abundance were determined during maize growth. At maturity 26.0% of straw N was assimilated by maize in the urea plus straw treatment. From the eighth leaf stage to maturity, urea plus straw had a significantly (P < 0.05) higher concentration and percentage of exogenous substrate N present as soil total N (TN), particulate organic N (PON), and mineral associated total N (MTN) in bulk and rhizosphere soils than the urea-only treatment. From silking to maturity in the urea plus straw treatment, rhizosphere soil significantly (P < 0.05) increased the percentage of exogenous substrate N present as inorganic N (Inorg-N) and MTN, and significantly (P < 0.05) decreased that present as PON and microbial biomass N (MBN) compared with the bulk soil. From the eighth leaf stage to maturity, rhizosphere soil significantly (P < 0.05) increased the percentage of straw N present as Inorg-N and MTN except for MTN at the silking stage, and significantly decreased (P < 0.05) that present as PON compared with the bulk soil. Overall, straw was an available N source to the crop, and the increase in straw N availability needs to be considered from the interaction of fertilization practices and the crop rhizosphere.
EVALUATION OF THE EFFECT OF MESENCHYMAL STEM CELLS ON CHEMOTHERAPY RESPONSE FOR NEUROBLASTOMA TREATMENT IN AN EXPERIMENTAL ANIMAL MODEL
Authors: Aktas Safiye , Olgun Yuksel , Evin Hande , Ercetin Ayse Pinar , Aktas Tekincan Cagri , Yilmaz Osman , Kirkim Gunay , Olgun Nur 
Published: November 2020

ABSTRACTHigh-dose cisplatin (CDDP) causes dose-limiting side effects in neuroblastoma (NB) treatment. Mesenchymal stem cells (MSC) are a current research area in cellular treatments due to multipotential characteristics. The aim of this study is to assess the interaction of MSC with CDDP in an athymic nude mouse NB model. Athymic male nude mice (n=28) were injected subcutaneously with C1300 NB cell line. After tumor growth to 1 cm diameter in 7-10 days, mice were randomly assigned to one of 4 experimental groups of control, CDDP treatment, MSC treatment and CDDP+MSC treatment with 7 mice in each group. Animals had basal auditory tests performed and had physiological serum or CDDP (20 mg/kg) injected into the peritoneum and were intravenously injected with 1×105MSC once. Seven days later, hearing tests were performed again and the animals were sacrificed. Tumor tissue was assessed in terms of necrosis, apoptosis and viability. Apoptosis was evaluated with annexin V+PI flow cytometry analysis and TUNEL. Additionally, the MSC rate within the tumor was assessed with flow cytometry for triple CD34+ CD44+ and CD117-expression. Additionally, liver, kidney, brain and cochlear tissue were analyzed with light microscopy in terms of systemic side effect profile. Expression of the cochlear cell proteins of calretinin, math-1 and myosin2A were immunohistochemically assessed in ear sections. Statistical analysis used the nonparametric Kruskal Wallis and Mann Whitney U tests with p<0.05 significance. Tumor tissues were found to have statistically significantly higher levels of necrosis in the CDDP group and CDDP+MSC group compared to the control and MSC groups (p=0.001, p=0.006). The CDDP+MSC group had lower tumor necrosis rates than the CDDP group but this was not observed to have statistical significance (p=0.05). MSC did not change the tumor dimensions in the CDDP group (p=0.557). The groups administered MSC had higher triple CD34+ CD44+ and CD117- expression within tumor tissue compared to the control and CDDP groups. In the inner ear, the expression of cochlear cell proteins calretinin, math-1 and myosin2A were identified to be highest in the groups administered MSC. Auditory tests observed that the 15-decibel loss at 12, 16, 20 and 32 kHz frequencies in both ears with CDDP was resolved with MSC administration. With this study, IV administration of MSC treatment was observed to prevent the hearing loss caused by CDDP without disrupting the antitumor effect of CDDP. Systemic MSC may be assessed for clinical use to reduce the side effects of CDDP.
Utility of cell-free DNA concentrations and illness severity scores to predict survival in critically ill neonatal foals
Authors: Colmer Sarah F. , Luethy Daniela , Abraham Michelle , Stefanovski Darko , Hurcombe Samuel D. 
Published: November 2020

ABSTRACTPlasma cell-free DNA (cfDNA) levels have been associated with disease and survival status in septic humans and dogs. To date, studies investigating cfDNA levels in association with critical illness in foals are lacking. We hypothesized that cfDNA would be detectable in the plasma of foals, that septic and sick-nonseptic foals would have significantly higher cfDNA levels compared to healthy foals, and that increased cfDNA levels would be associated with non-survival. Animals used include 80 foals of 10 days of age or less admitted to a tertiary referral center between January and July, 2020 were stratified into three categories: healthy (n=34), sick non-septic (n=11) and septic (n=35) based on specific criteria. This was a prospective clinical study. Blood was collected from critically ill foals at admission or born in hospital for cfDNA quantification and blood culture. Previously published sepsis score (SS) and neonatal SIRS score (NSIRS) were also calculated. SS, NSIRS, blood culture status and cfDNA concentrations were evaluated to predict survival. Continuous variables between groups were compared using Kruskal-Wallis ANOVA with Dunn’s post hoc test. Comparisons between two groups were assessed using the Mann-Whitney U-test or Spearman rank for correlations. The performance of cfDNA, sepsis score and NSIRS score to predict survival was assessed by receiver operator characteristic (ROC) curve analysis including area under the curve, sensitivity and specificity using cutoffs. Plasma cfDNA was detectable in all foals. No significant differences in cfDNA concentration were detected between healthy foals and septic foals (P=0.65) or healthy foals and sick non-septic foals (P=0.88). There was no significant association between cfDNA and culture status, SS, NSIRS or foal survival. SS (AUC 0.85) and NSIRS (AUC 0.83) were superior to cfDNA (AUC 0.64) in predicting survival. cfDNA was detectable in foal plasma however offers negligible utility to diagnose sepsis or predict survival in critical illness in neonates.
Sequential dynamics of Stearoyl-CoA Desaturase-1(SCD1) /ligand binding and unbinding mechanism: A computational study
Authors: Petroff Anna B. , Weir Rebecca L. , Yates Charles R. , Ng Joseph D. , Baudry Jerome 
Published: November 2020

AbstractStearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as apoprotein. The modeling of SCD1:fatty acid interactions suggests that 1) SCD1:CoA moiety interactions open the substrate binding tunnel, 2) SCD1 stabilizes a substrate conformation favorable for desaturation, and 3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.
Assessment of heterotic potential and combining ability of immortal restorer lines derived from an elite rice hybrid, KRH-2, for the development of superior rice hybrids
Authors: Kulkarni Swapnil Ravindra , SM Balachandran , RA Fiyaz , K Sruthi , Balakrishnan Divya , K Ulaganathan , A.S. Hari Prasad , RM Sundaram 
Published: November 2020

AbstractPresent investigation was carried out to assess the heterotic potential and combining ability of immortal restorer lines [consisting of two recombinant inbred lines (RILs) and two doubled haploid lines (DHLs)] developed from an elite rice hybrid, KRH-2 by crossing them with three popular WA-CMS lines, IR58025A, CRMS32A and APMS6A through line × tester analysis. The doubled haploid line 1 (DHL-1) was observed to be a good general combiner for total grain yield per plant (YLD) and other yield component traits and among the CMS lines, IR58025A was observed to be the best combiner as it showed positive significant values for the traits viz., total grain yield per plant, panicle length and spikelet fertility. Higher preponderance of the variance associated with specific combining ability (SCA) as compared to general combining ability (GCA) variance was observed for most of the traits indicated the predominant role of non-additive gene action in the expression of the traits. Out of twelve novel crosses between the immortal restorer lines derived from KRH-2 and the WA-CMS lines, 66.66% (eight crosses) showed significant and desirable SCA effects for the traits viz., total grain yield per plant, days to fifty percent flowering, plant height, flag leaf length, flag leaf width, number of filled grains per panicle and spikelet fertility. Two crosses IR58025A/RIL-24 and CRMS32A/RIL-24 were observed to be the most promising cross combinations showing standard heterosis of >50% for YLD trait (as compared with KRH-2) with higher prevalence of GCA and SCA, respectively. Heterotic yield advantage of IR58025A/RIL-24 and CRMS32A/RIL-24 was 77.05% and 54.74%, respectively over KRH-2 and these can be utilized for developing commercial hybrids. The present study also indicates the potentiality of RILs in providing useful parental lines for developing heterotic hybrids which are hard to get from outside sources in the new intellectual property regime.
Evaluation of the Abbott ARCHITECT HIV Ag/Ab Combo Assay for Determining Recent HIV-1 Infection
Authors: Curtis Kelly A. , Rudolph Donna L. , Pan Yi , Delaney Kevin , Anastos Kathryn , DeHovitz Jack , Kassaye Seble G. , Hanson Carl V. , French Audrey L. , Golub Elizabeth , Adimora Adaora A. , Ofotokun Igho , Bolivar Hector , Kempf Mirjam-Colette , Peters Philip J. , Switzer William M. 
Published: November 2020

BackgroundGiven the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States.MethodsIn this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs.ResultsThe MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination.ConclusionDual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.