bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance of endothelial cells to SARS-CoV-2 infectionin vitro
Authors: Ahmetaj-Shala Blerina , Peacock Thomas P. , Baillon Laury , Swann Olivia C. , Gashaw Hime , Barclay Wendy S. , Mitchell Jane A.
Published: November 2020

Rationale

The secondary thrombotic/vascular clinical syndrome of COVID-19 suggests that SARS-CoV-2 infects not only respiratory epithelium but also the endothelium activating thrombotic pathways, disrupting barrier function and allowing access of the virus to other organs of the body. However, a direct test of susceptibility to SARS-CoV-2 of authentic endothelial cell lines has not been performed.

Objective

To determine infectibility of primary endothelial cell lines with live SARS-CoV-2 and pseudoviruses expressing SARS-CoV-2 spike protein.

Methods and Results

Expression of ACE2 and BSG pathways genes was determined in three types of endothelial cells; blood outgrowth, lung microvascular and aortic endothelial cells. For comparison nasal epithelial cells, Vero E6 cells (primate kidney fibroblast cell line) and HEK 293T cells (human embryonic kidney cells) transfected with either ACE2 or BSG were used as controls. Endothelial and Vero E6 cells were treated with live SARS-CoV-2 virus for 1 hour and imaged at 24 and 72 hours post infection. Pseudoviruses containing SARS-CoV-2, Ebola and Vesicular Stomatis Virus glycoproteins were generated and added to endothelial cells and HEK 239Ts for 2 hours and infection measured using luminescence at 48 hours post infection. Compared to nasal epithelial cells, endothelial cells expressed low or undetectable levels of ACE2 and TMPRSS2 but comparable levels of BSG, PPIA and PPIB. Endothelial cells showed no susceptibility to live SARS-CoV-2 or SARS-CoV-2 pseudovirus (but showed susceptibility to Ebola and Vesicular Stomatitis Virus). Overexpression of ACE2 but not BSG in HEK 239T cells conferred SARS-CoV-2 pseudovirus entry. Endothelial cells primed with IL-1ß remained resistant to SARS-CoV-2.

Conclusion

Endothelial cells are resistant to infection with SARS-CoV-2 virus, in line with relatively low levels of ACE2 and TMPRSS2, suggesting that the vascular dysfunction and thrombosis seen in severe COVID-19 is a result of factors released by adjacent infected cells (e.g. epithelial cells) and/or circulating, systemic inflammatory mediators.
Revision of Indian Bipaliid species with description of a new species,Bipalium bengalensisfrom West Bengal, India (Platyhelminthes: Tricladida: Terricola)
Authors: Bhakat Somnath
Published: November 2020

A new species of Bipaliid land planarian,Bipalium bengalensisis described from Suri, West Bengal, India. The species is jet black in colour without any band or line but with a thin indistinct mid-dorsal groove. Semilunar head margin is pinkish in live condition with numerous eyes on its margin. Body length (BL) ranged from 19.00 to 45.00mm and width varied from 9.59 to 13.16% BL. Position of mouth and gonopore from anterior end ranged from 51.47 to 60.00% BL and 67.40 to 75.00 % BL respectively. Comparisons were made with its Indian as well as Bengal congeners.

Salient features, distribution and biometric data of all the 29 species of Indian Bipaliid land planarians are revised thoroughly. Genus controversy in Bipaliid taxonomy is critically discussed and a proposal of only two generaBipaliumandHumbertiumis suggested.
Beta and theta oscillations correlate with subjective time during musical improvisation in ecological and controlled settings: a single subject study
Authors: Farrugia Nicolas , Lamouroux Alix , Rocher Christophe , Bouvet Jules , Lioi Giulia
Published: November 2020

In this paper, we describe the results of a single subject study attempting at a better understanding of the subjective state during musical improvisation. In a first experiment, we setup an ecological paradigm measuring EEG on a musician in free improvised concerts with an audience, followed by retrospective rating of the mental state of the improviser. We introduce Subjective Temporal Resolution (STR), a retrospective rating assessing the instantaneous quantization of subjective timing of the improviser. We identified high and low STR states using Hidden Markov Models in two performances, and were able to decode those states using supervised learning on instantaneous EEG power spectrum, showing increases in theta and alpha power with high STR values. In a second experiment, we found an increase of theta and beta power when experimentally manipulating STR in a musical improvisation imagery experiment. These results are interpreted with respect to previous research on flow state in creativity, as well as with the temporal processing literature. We suggest that a component of the subjective state of musical improvisation may be reflected in an underlying mechanism related to the subjective quantization of time. We also demonstrate the feasibility of single case studies of musical improvisation using brain activity measurements and retrospective reports, by obtaining consistent results across multiple sessions.
Retardation of folding rates of substrate proteins in the nanocage of GroEL
Authors: Koculi Eda , Thirumalai D.
Published: November 2020

TheE. Coli. ATP-consuming chaperonin machinery, a complex between GroEL and GroES, has evolved to facilitate folding of substrate proteins (SPs) that cannot do so spontaneously. A series of kinetic experiments show that the SPs are encapsulated in the GroEL/ES nano cage for a short duration. If confining the SPs in the predominantly polar cage of GroEL in order to help folding, the assisted folding rate, relative to the bulk value, shouldalwaysbe enhanced. Here, we show that this is not the case for the folding of rhodanese in the presence of the full machinery of GroEL/ES and ATP. The assisted folding rate of rhodanese decreases. Based on our finding and those reported in other studies, we suggest that the ATP-consuming chaperonin machinery has evolved to optimize the product of the folding rate and the yield of the folded SPs on the biological time scale. Neither the rate nor the yield is separately maximized.
Evolution of the complex transcription network controlling biofilm formation inCandidaspecies
Authors: Mancera Eugenio , Nocedal Isabel , Hammel Stephen , Gulati Megha , Mitchell Kaitlin F. , Andes David R. , Nobile Clarissa J. , Butler Geraldine , Johnson Alexander D.
Published: November 2020

We examine how a complex transcription network composed of seven “master” regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in severalCandidaspecies, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. The ability to form biofilms is crucial for microbial colonization of different host niches, particularly when an implanted medical device is present. We examined and compared the network underlying biofilm formation across fourCandidaspecies (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis), all of which form biofilms composed of multiple cell types. To describe the salient features of the network across different species, we employed four approaches: (1) we phenotypically characterized the biofilms formed by these species using a variety of methods; (2) we knocked out — one by one — the master regulators identified inC. albicansin the four species and monitored their effect on biofilm formation; (3) we identified the target genes of 18 master regulator orthologs across the four species by performing ChIP-seq experiments; and (4) we carried out transcriptional profiling across each species during biofilm formation. Additional network information was obtained by analyzing an interspecies hybrid formed between the two most closely related species,C. albicansandC. dubliniensis. We observed two major types of changes that have occurred in the biofilm circuit since the four species last shared a common ancestor. Master regulator “substitutions” occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. Both types of change are crucial to account for the structures of the biofilm networks in extant species. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.
Impact network analysis and the INA R package: Decision support for regional management interventions
Authors: Garrett K. A.
Published: November 2020

The success of intervention projects in ecological systems depends not only on the quality of management technologies, but also patterns of adoption among land managers. Impact network analysis (INA) is a new framework for evaluating the likely success of regional interventions before, during, and after projects, for project implementers, policy makers, and funders. INA integrates across three key system components in a multilayer network analysis: (a) the quality of a management technology and the quality of research supporting it, (b) the socioeconomic networks through which managers learn about management technologies and decide whether to use them, and (c) the linked biophysical network for target species success or failure in the management landscape that results from managers’ decisions.

The specific objectives of this paper are (1) to introduce the INA framework and INA R package, (2) to illustrate identification of key nodes for smart surveillance, for networks where the likelihood of invasive species entry into the biophysical network at a given node may be based on information available to the corresponding node in the socioeconomic network, (3) to illustrate application of the INA framework for evaluating the likely degree of success of a project in intervention ecology, before, during and after an intervention, and (4) to illustrate the use of INA for evaluating adaptation strategies under global change scenarios with pulse and press stressors, introducing ‘adaptation functions’ for sustainability and resilience.

Examples of use of the INA package show one of the key outcomes of analyses: identifying when systems may be non-responsive to the system components that are readily changed through management decisions, to explore what additional adaptations may be necessary for intervention success.

The broader goal for the development of impact network analysis and the INA package is to provide a common framework that integrates across intervention ecology, to enhance opportunities for lessons learned across systems and scientific disciplines, to support the development of a community of practice, and to create a general platform for analysis of sustainability, resilience, and economic viability in intervention ecology applications.
Virucidal efficacy of different formulations for hand and surface disinfection targeting SARS CoV-2
Authors: Steinhauer Katrin , Meister Toni Luise , Todt Daniel , Krawczyk Adalbert , Paßvogel Lars , Becker Britta , Paulmann Dajana , Bischoff Birte , Eggers Maren , Pfaender Stephanie , Brill Florian H H , Steinmann Eike
Published: November 2020

In the ongoing SARS CoV-2 pandemic effective measures are needed, and guidance based on the methodological framework of the European committee for standardization (CEN) can help to choose effective disinfectants on an immediate basis. This study demonstrates that two commercially available formulations for surface disinfection and one formulation for hand disinfection claiming“virucidal activity against enveloped viruses”are effectively inactivating SARS-CoV-2. This study emphasizes that chemical disinfectants claiming“virucidal activity against enveloped viruses”are an effective choice to target enveloped SARS-CoV-2 as a preventive measure.
Critical appraisal of the European Union Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) Preliminary Opinion on electronic cigarettes
Authors: O’Leary R. , Polosa R. , Li Volti G.
Published: November 2020

Background

In preparation for the 2021 revision of the European Union Tobacco Products Directive, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) has posted its Preliminary Opinion on Electronic Cigarettes. They conclude that e-cigarettes only achieve a sub-optimal level of protection of human health. In this paper we provide evidence that Opinion’s conclusions are not adequately backed up by scientific evidence and totally disregard the potential health benefits of using alternative combustion-free nicotine containing products as substitute for tobacco cigarettes.

Method

Searches for articles were conducted in PubMed and by citation chasing in Google Scholar. Articles were also retrieved with a review of references in major publications. Primary data from World Health Organization surveys, the conclusions of reviews, and peer-reviewed non-industry studies were cited to address errors and omissions identified in the Opinion.

Results

The Opinion omitted reporting on the individual and population health benefits of the substitution of e-cigarettes (ENDS) for cigarette smoking. Alternative hypotheses to the gateway theory were not evaluated. Its assessment of cardiovascular risk is contradicted by numerous reviews. It exhibits biases in its statements from the measurements selected on the frequency of use. It did not report non-nicotine use. It misrepresented trends in ENDS prevalence. It over-emphasized the role of flavours in youth ENDS initiation. It did not discuss cessation in sufficient length.

Conclusions

For the delivery of a robust and comprehensive final report, the members of the Working Group of the Scientific Committee on Health, Environmental and Emerging Risks will need to consider (1) the potential health benefits of ENDS substitution for cigarette smoking, (2) alternative hypotheses and contradictory studies on the gateway effect, (3) its assessment of cardiovascular risk, (4) biases arising from the measurements of frequency of use, (5) non-nicotine use, (6) the role of flavours, and (7) a fulsome discussion of cessation.
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

Multisystem 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.

Highlights

Multisystem Inflammatory Disease in Children (MIS-C) patients exhibit T cell receptor (TCR) repertoire skewing, with expansion of T cell Receptor Beta Variable gene (TRBV)11-2

TRBV11-2 skewing correlates with MIS-C severity and cytokine storm

J gene/CDR3 diversity in MIS-C patients is compatible with a superantigen selection process

In 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

Migratory 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

Background

The 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.

Methods

TRPM2 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.

Results

Overexpressed 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.

Conclusion

TRPM2 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.
Analyzing brain data by sex: Are we asking the right question?
Authors: Alon Nitay , Meilijson Isaac , Joel Daphna
Published: November 2020

The authors have withdrawn their manuscript because in revising it following a Reviewer’s comment, they realized the data no longer suit one of their requirements. Specifically, the Reviewer noted that they had a mistake in their code for ‘correction’ for brain size. Following this correction, the authors realized that most of the ‘corrected’ measures do not fit a Gaussian distribution, thereby rendering their approach mathematically unjustified. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
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

Soil 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.

Availability

Installation 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

Social 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

In 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

Lower 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

A15N 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

High-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

Plasma 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

Stearoyl-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

Present 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

Background

Given 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.

Methods

In 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.

Results

The 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.

Conclusion

Dual-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.
Comparative Transcriptomic Analysis Revealed Complex Molecular Mechanisms Underlying Pests, Pathogens Resistance and Seed Development in Wild and Cultivated Blackgram
Authors: Raizada Avi , Jegadeesan Souframanien
Published: November 2020

Blackgram is a widely cultivated pulse crop in Asia. Bruchid pests and yellow mosaic disease (YMD) causes huge loss in legume production including blackgram. Blackgram wild accession (Vigna mungo var.silvestris), Trombay wild urd (INGR10133) conferred resistance to bruchids especiallyCallosobruchus maculatus, through antibiosis. However, the mechanisms still remains uncharacterized. We performed the comparative transcriptome analysis of the developing seeds of wild and cultivated blackgram with contrasting phenotypes for 3 traits, bruchids infestation, YMD and seed size. In this study,715differentially expressed genes(DEGs) were re-annotated with reference to NCBI nr database. RNA-Seq was validated by quantitative real-time PCR for 22 DEGs. In Trombay wild, defense related components such as acid phosphatase, vicilins, trypsin inhibitor, brassinosteroid signalling components were found up-regulated. While in cultivar, transcripts forLEA, cysteine protease, autophagy related proteins(ATG3, ATG5, ATG8C and ATG1t),DnaJ, tobamovirus multiplication protein, downy mildew resistance protein, LRR/F-box proteins were found up-regulated. In TW, three transcripts were found common for both bruchids pest and geminivirus resistance (LRR receptor kinase, transmembrane protein 87b and thaumatin like protein).Our study is the first report on transcriptomic differences between wild and cultivated blackgram with new insights into the molecular networks underlying seed development, resistance to pests and pathogens.
Potential ofin vivo- andin vitro-cultured entomopathogenic nematodes to infectLobesia vanillana(Lepidoptera: Tortricidae) under laboratory conditions
Authors: du Preez Francois , Malan Antoinette Paula , Addison Pia
Published: November 2020

Thein vivo- andin vitro-cultured South African entomopathogenic nematodes (EPNs),Steinernema yirgalemenseandSteinernema jeffreyense(Rhabditida: Steinernematidae), were evaluated against larvae and pupae ofLobesia vanillanain laboratory bioassays. For larvae, high mortality was observed for all treatments:In vitro-culturedS. yirgalemense(98%) performed better thanS. jeffreyense(73%), while withinin vivocultures, there was no difference between nematode species (both 83%). No significant difference was detected betweenin vivo- andin vitrocultures of the same nematode species. The LD50of thein vitro-culturedS. yirgalemense, the best performing species, was 7.33 nematodes per larva. Mortality by infection was established by dissecting cadavers and confirming the presence of nematodes, which was > 90% for all treatments. Withinin vitrocultures, bothS. yirgalemenseandS. jeffreyensewere able to produce a new cohort of infective juveniles fromL. vanillanalarvae. Pupae, however, were found to be considerably less susceptible to EPN infection. The relative success of localin vivo- andin vitro-cultured EPN species against a tortricid species in laboratory assays is encouraging for further research and development of this technology.
Study on the efficacy ofCynodon dactylonagainst Infectious Myonecrosis Virus (IMNV) inPenaeus vannamei
Authors: Jha Rajeev Kumar , Wisoyo Soy Daniel , Kristina  , Srisombat Sarayut
Published: November 2020

Infectious myonecrosis virus (IMNV) is one of the most pathogenic viruses causing severe mortality inPenaeus vannameiin many countries. Several strategies have been implemented to inhibit the presence of IMNV disease. The present study was carried out to examine the antiviral activity ofCynodon dactylonethanolic extract on IMNV disease in shrimp byin vivotesting. TheC. dactylonplant extract was incorporated with artificial pellet feed at a concentration of 10, 15%, 20%, and 25%. For the experimental challenge shrimp were fed with IMNV-infected shrimp meat. The antiviral activity was determined by observing survival rates, and IMNV infection was confirmed at the end of the experiment through polymerase chain reaction (PCR) identification. This study showed that the plant extract ofC. dactylonwas found to be highly effective in preventing IMNV infection with up to 98% survival rate inPenaeus vannamei.
SARS-CoV-2 epitope mapping on microarrays highlights strong immune-response to N protein region
Authors: Musicò Angelo , Frigerio Roberto , Mussida Alessandro , Barzon Luisa , Sinigaglia Alessandro , Riccetti Silvia , Gobbi Federico , Piubelli Chiara , Bergamaschi Greta , Chiari Marcella , Gori Alessandro , Cretich Marina
Published: November 2020

A workflow for SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 Spike (S), Nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155-171) providing 92% sensitivity and 100% specificity of IgG detection in Covid-19 samples thus being a promising candidate for rapid implementation in serological tests.
POINT Technology Illuminates the Processing of Polymerase-Associated Intact Nascent Transcripts
Authors: Sousa-Luis Rui , Dujardin Gwendal , Zukher Inna , Kimura Hiroshi , Carmo-Fonseca Maria , Proudfoot Nick J , Nojima Takayuki
Published: November 2020

Mammalian chromatin is the site of both RNA polymerase II (Pol II) transcription and coupled RNA processing. However, molecular details of such co-transcriptional mechanisms remain obscure, partly due to technical limitations in purifying authentic nascent transcripts. We present a new approach to purify and profile nascent RNA, called Polymerase Intact Nascent Transcript (POINT) technology. This three-pronged methodology maps nascent RNA 5’ends (POINT-5), establishes the kinetics of co-transcriptional splicing patterns (POINT-nano) and profiles whole transcription units (POINT-seq). In particular we show by depletion of the nuclear exonuclease Xrn2 that this activity acts selectively on cleaved 5’P-RNA at polyadenylation sites. Furthermore POINT-nano reveals that splicing occurs either immediately after splice site transcription or is delayed until Pol II transcribes downstream sequences. Finally, we connect RNA cleavage and splicing with either premature or full-length transcript termination. We anticipate that POINT technology will afford full dissection of the complexity of co-transcriptional RNA processing.

HIGHLIGHTS

POINT methodology dissects intact nascent RNA processing

Specificity of Xrn2 exonuclease in co-transcriptional RNA degradation

Splicing suppresses Xrn2-dependent premature termination

Different kinetic classes of co-transcriptional splicing in human genes
PathDSP: Explainable Drug Sensitivity Prediction through Cancer Pathway Enrichment
Authors: Tang Yi-Ching , Gottlieb Assaf
Published: November 2020

Computational approaches to predict drug sensitivity can promote precision anticancer therapeutics. Generalizable and explainable models are of critical importance for translation to guide personalized treatment and are often overlooked in favor of prediction performance.

Here, we propose a pathway-based model for drug sensitivity prediction that integrates chemical structure information with enrichment of cancer signaling pathways across drug-associated genes, gene expression, mutation and copy number variation data to predict drug response on the Genomics of Drug Sensitivity in Cancer (GDSC) dataset. Using a deep neural network, we outperforming state-of-the-art deep learning models, while demonstrating good generalizability a separate dataset of the Cancer Cell Line Encyclopedia (CCLE) as well as provide explainable results, demonstrated through case studies that are in line with current knowledge. Additionally, our pathway-based model achieved a good performance when predicting unseen drugs and cells, with potential utility for drug development and for guiding individualized medicine.
An End-to-end Oxford Nanopore Basecaller Using Convolution-augmented Transformer
Authors: Lv Xuan , Chen Zhiguang , Lu Yutong , Yang Yuedong
Published: November 2020

Oxford Nanopore sequencing is fastly becoming an active field in genomics, and it’s critical to basecall nucleotide sequences from the complex electrical signals. Many efforts have been devoted to developing new basecalling tools over the years. However, the basecalled reads still suffer from a high error rate and slow speed. Here, we developed an open-source basecalling method, CATCaller, by simultaneously capturing global context through Attention and modeling local dependencies through dynamic convolution. The method was shown to consistently outper-form the ONT default basecaller Albacore, Guppy, and a recently developed attention-based method SACall in read accuracy. More importantly, our method is fast through a heterogeneously computational model to integrate both CPUs and GPUs. When compared to SACall, the method is nearly 4 times faster on a single GPU, and is highly scalable in parallelization with a further speedup of 3.3 on a four-GPU node.