bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the neural basis of fear produced by mental imagery: imaginal exposure in individuals fearful of spiders
Authors: Hoppe Johanna M. , Holmes Emily A. , Agren Thomas
Published: December 2020

Imaginal exposure, i.e. reducing fear using exposure to mental imagery, is a widely used psychological treatment technique for dysfunctional fears. Yet, little is known about its underlying neural mechanisms. The present study examines the neural basis of imaginal exposure using a novel experimental procedure consisting of repeated exposure to flashpoint mental imagery of phobic (spiders) and neutral (gloves) stimuli. Whether the 10 min long imaginal exposure procedure could reduce fear responses was examined one week later. Thirty participants fearful of spiders underwent the experimental procedure. Neural activity was assessed using functional magnetic resonance imaging (session 1). Subjective fear and skin conductance responses were measured throughout the study (sessions 1 and 2). Imaginal exposure evoked intense fear and heightened skin conductance responses, and indicated robust activation in several brain regions, including amygdala, midcingulate cortex and insula. Findings demonstrate that neural activity in fear-processing brain areas can be elicited solely by generating a mental image of a phobic stimulus, that is, in the absence of the percept. Relevant for treatment development, results reveal that a single 10 min session of brief exposures to flashpoint mental imagery can lead to lasting reductions in phobic fear at both the subjective and physiological levels.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.
Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Authors: Horby Peter W , Roddick Alistair , Spata Enti , Staplin Natalie , Emberson Jonathan R , Pessoa-Amorim Guilherme , Peto Leon , Campbell Mark , Brightling Christopher , Prudon Ben , Chadwick David , Ustianowski Andrew , Ashish Abdul , Todd Stacy , Yates Bryan , Buttery Robert , Scott Stephen , Maseda Diego , Baillie J Kenneth , Buch Maya H , Chappell Lucy C , Day Jeremy N , Faust Saul N , Jaki Thomas , Jeffery Katie , Juszczak Edmund , Lim Wei Shen , Montgomery Alan , Mumford Andrew , Rowan Kathryn , Thwaites Guy , Mafham Marion , Haynes Richard , Landray Martin J ,   RECOVERY Collaborative Group
Published: December 2020

Background

Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19.

Methods

In this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).

Findings

Between 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54).

Interpretation

In patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Analysing economic costs of invasive alien species with the invacost R package
Authors: Leroy Boris , Kramer Andrew M. , Vaissière Anne-Charlotte , Kourantidou Melina , Courchamp Franck , Diagne Christophe
Published: December 2020

The reported costs of invasive alien species from the global database InvaCost are heterogenous and cover different spatio-temporal scales. A standard procedure for aggregating invasive species cost estimates is necessary to ensure the repeatability and comparativeness of studies.

We introduce here theinvacostR package, an open-source software designed to query and analyse the InvaCost database. We illustrate this package and its framework with cost data associated with invasive alien invertebrates.

First, theinvacostpackage provides updates of this dynamic database directly in the analytical environment R. Second, it helps understand the heteregoneous nature of monetary cost data for invasive species, processes to harmonize the data, and the inherent biases associated with such data. Third, it readily provides complementary methods to investigate the costs of invasive species at different scales, all the while accounting for econometric statistical issues.

This tool will be useful for scientists working on invasive alien species, by (i) facilitating access to and use of this multi-disciplinary data resource and (ii) providing a standard procedure which will facilitate reproducibility and comparability among studies, one of the major critics of this topic until now. It should facilitate further interdisciplinary works including economists and invasion ecology researchers.
Baby makes three: maternal, paternal, and zygotic genetic effects shape larval phenotypic evolution
Authors: Zakas Christina , Rockman Matthew V.
Published: December 2020

The evolutionary potential of a population is shaped by the genetic architecture of its life-history traits. Early-life phenotypes are influenced by both maternal and offspring genotype, and efforts to understand life-history evolution therefore require consideration of the interactions between these separate but correlated genomes. We used a four-generation experimental pedigree to estimate the genetic architecture of early-life phenotypes in a species with dramatic variation in larval size and morphology. In the polychaete annelidStreblospio benedicti, females make either many small eggs that develop into complex larvae that feed in the plankton or few large eggs that develop into benthic juveniles without having to feed as larvae. By isolating the contributions of maternal, paternal, and zygotic genotype to larval traits, we determined that larval anatomical structures are governed by the offspring genotype at a small number of large-effect loci. Larval size is not shaped by the larva’s own genotype but instead depends on loci that act in the mother, and at two genomic locations, by loci that act in the father. The overall phenotype of each larva thus depends on three separate genomes, and a population’s response to selection on larval traits will reflect the interactions among them.
Allosteric conformational ensembles have unlimited capacity for integrating information
Authors: Biddle John W. , Martinez-Corral Rosa , Wong Felix , Gunawardena Jeremy
Published: December 2020

Integration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained by pairwise cooperativities, in which binding is modulated by binding at another site. Higher-order cooperativities (HOCs), in which binding is collectively modulated by multiple other binding events, appears to be necessary but an appropriate mechanism has been lacking. We show here that HOCs arise through allostery, in which effective cooperativity emerges indirectly from an ensemble of dynamically-interchanging conformations. Conformational ensembles play important roles in many cellular processes but their integrative capabilities remain poorly understood. We show that sufficiently complex ensembles can implement any form of information integration achievable without energy expenditure, including all HOCs. Our results provide a rigorous biophysical foundation for analysing the integration of binding information through allostery. We discuss the implications for eukaryotic gene regulation, where complex conformational dynamics accompanies widespread information integration.
Cellular adaptation and the importance of the purine biosynthesis pathway during biofilm formation in Gram-positive pathogens
Authors: Gélinas Martin , Museau Léa , Milot Arielle , Beauregard Pascale B.
Published: December 2020

Bacterial biofilms are involved in chronic infections and confer 10 to 1000 times more resistance to antibiotics, leading to treatment failure and complications. When transitioning from a planktonic lifestyle to biofilms, certain Gram-positive bacteria are likely to modulate several cellular pathways including central carbon metabolism, primary biosynthesis pathways and production of secondary metabolites. These metabolic adaptations might play a crucial role in biofilm formation by Gram-positive pathogens such asStaphylococcus aureusandEnterococcus faecalis. Here, we performed a transcriptomic approach to identify cellular pathways that might be similarly regulated during biofilm formation in these bacteria. Different strains and biofilm-inducing media were used to identify a set of regulated genes that are common and independent of the environment or accessory genomes analysed. The gene set enrichment analysis of the transcriptome of four different strains of Gram-positive bacteria identified biosynthesis of secondary metabolites, biosynthesis of antibiotics and purine biosynthesis as three commonly upregulated pathways in biofilm. Our approach did not highlight downregulated pathways during biofilm formation that were common toS. aureusandE. faecalis. Of the three upregulated pathways, thede novoIMP biosynthesis pathway constitutes a promising target of cellular adaptation during biofilm formation. Gene deletions in this pathway, particularlypurN, purL, purQ, purHandpurMsignificantly impaired biofilm formation ofS. aureus.

Importance

Biofilms are often involved in nosocomial infections and can cause serious chronic infections if not treated properly. Current anti-biofilm strategies rely on antibiotic usage, but they have a limited impact because of the biofilm’s intrinsic resistance to drugs. Metabolism remodelling likely plays a central role during biofilm formation, but it is still unclear if these cellular adaptations are shared between strains and species. Using comparative transcriptomics of different strains ofStaphylococcus aureusandEnterococcus faecalis, we identified a core of commonly regulated genes during biofilm formation. Interestingly, we observed that thede novoIMP biosynthesis was systematically upregulated during biofilm formation. This pathway could constitute an interesting new anti-biofilm target to increase the host spectrum, drug efficiency and prevent resistance evolution. These results are also relevant to a better understanding of biofilm physiology.
Uncovering the Structure and Function of Microbial Communities Formed During Periodic Tilling of TNT and DNT Co-Contaminated Soils
Authors: Keshani-Langroodi Saeed , Lan Yemin , Stenuit Ben , Rosen Gail , Hughes Joseph B. , Alvarez-Cohen Lisa , Sales Christopher M.
Published: December 2020

1.

Environmental contamination by 2,4,6-trinitrotoluene (TNT), historically the most widely used secondary explosive, is a long-standing problem in former military conflict areas and at manufacturing and decommissioning plants. In field test plots at a former explosives manufacturing site, removal of TNT and dinitrotoluenes (DNTs) was observed following periods of tillage. Since tilling of soils has previously been shown to alter the microbial community, this study was aimed at understanding how the microbial community is altered in soils with historical contamination of nitro explosives from the former Barksdale TNT plant. Samples of untilled pristine soils, untilled TNT-contaminated soils and tilled TNT-contaminated soils were subjected to targeted amplicon sequencing of 16S ribosomal RNA genes in order to compare the structure of their bacterial communities. In addition, metagenomic data generated from the TNT tilled soil was used to understand the potential functions of the bacterial community relevant to nitroaromatic degradation. While the biodiversity dropped and theBurkholderialesorder became dominant in both tilled and untilled soil regardless of tillage, the bacterial community composition at finer taxonomic levels revealed a greater difference between the two treatments. Functional analysis of metagenome assembled genome (MAG) bins through systematic review of commonly proposed DNT and TNT biotransformation pathways suggested that both aerobic and anaerobic degradation pathways were present. A proposed pathway that considers both aerobic and anaerobic steps in the degradation of TNT in the scenario of the tilled contaminated soils is presented.

2.

Importance

In this study, TNT and DNT removal has been observed in field-scale experiments following periodic tilling of historically contaminated soils. The microbial community structures of uncontaminated pristine soils, untilled contaminated soils, and tilled contaminated soils were investigated using high-throughput sequencing platforms. In addition, shotgun metagenome libraries of samples from tilled contaminated soils were generated. The results indicated that a significant shift of the bacterial community at the family level between tilled and untilled contaminated soils, with tilled soils being dominated byAlcaligenaceaeand untilled soils byBurkholderiacea.In-depth metagenomic analysis of samples from tilled contaminated soils, indicate the presence of genes that encode for enzymes that potentially could lead to mineralization of TNT and DNT under mixed aerobic and anaerobic periods.
Association of Structural Variation with Cardiometabolic Traits in Finns
Authors: Chen Lei , Abel Haley J. , Das Indraniel , Larson David E. , Ganel Liron , Kanchi Krishna L. , Regier Allison A. , Young Erica P. , Kang Chul Joo , Scott Alexandra J , Chiang Colby , Wang Xinxin , Lu Shuangjia , Christ Ryan , Service Susan K. , Chiang Charleston W.K. , Havulinna Aki S. , Kuusisto Johanna , Boehnke Michael , Laakso Markku , Palotie Aarno , Ripatti Samuli , Freimer Nelson B. , Locke Adam E. , Stitziel Nathan O. , Hall Ira M.
Published: December 2020

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low frequency SVs for association with 116 quantitative traits, and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including two novel loci at which SVs have strong phenotypic effects: (1) a deletion of theALBgene promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p=1.47×10−54), and is also associated with increased levels of total cholesterol (p=1.22×10−28) and 14 additional cholesterol-related traits, and (2) a multiallelic copy number variant (CNV) atPDPRthat is strongly associated with pyruvate (p=4.81×10−21) and alanine (p=6.14×10−12) levels and resides within a structurally complex genomic region that has accumulated many rearrangements over evolutionary time. We also confirmed six previously reported associations, including five led by stronger signals in single nucleotide variants (SNVs), and one linking recurrentHPgene deletion and cholesterol levels (p=6.24×10−10), which was also found to be strongly associated with increased glycoprotein level (p=3.53×10−35). Our study confirms that integrating SVs in trait-mapping studies will expand our knowledge of genetic factors underlying disease risk.
Rrp6p/Rrp47p constitutes an independent nuclear turnover system of mature small non-coding RNAs inSaccharomyces cerevisiae
Authors: Chaudhuri Anusha , Das Subhadeep , Banerjea Mayukh , Das Biswadip
Published: December 2020

InSaccharomyces cerevisiae,the nuclear exosome/Rrp6p/TRAMP participates in the 3’-end processing of several precursor non-coding RNAs. Here we demonstrate that the depletion of nucleus-specific 3’→5’ exoribonuclease Rrp6p and its cofactor, Rrp47p led to the specific and selective enhancement of steady-state levels of mature small non-coding RNAs (sncRNAs) that include 5S and 5.8S rRNAs, snRNAs and snoRNAs, but not 18S and 25S rRNAs. Most importantly, their steady-state enhancement does not require the exosome, TRAMP, CTEXT, or Rrp6p-associated Mpp6p. Rrp6p/47p-dependent enhancement of the steady-state levels of sncRNAs is associated with the diminution of their nuclear decay-rate and requires their polyadenylation before targeting by Rrp6p, which is catalyzed by both the canonical and non-canonical poly(A) polymerases, Pap1p and Trf4p. Consistent with this finding, we also demonstrated that Rrp6p and Rrp47p exist as an exosome-independent complex. Thus, Rrp6p-Rrp47p defines a core nuclear exosome-independent novel turnover system that targets the small non-coding RNAs.
Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice
Authors: Bennett Calli , Green Jacalyn , Ciancio Mae , Goral Joanna , Pitstick Lenore , Pytynia Matthew , Meyer Alice , Kwatra Neha , Jadavji Nafisa M.
Published: December 2020

Objective

One-carbon metabolism is a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. There are sex differences in hepatic one-carbon metabolism. However, it is unclear whether there are sex differences in dietary deficiencies of one-carbon metabolism in the brain. The aim of this study was to investigate if sex modulates the effects of dietary folic acid deficiency in brain tissue using a mouse model.

Methods

Male and female C57Bl/6J mice were placed on a folic acid deficient (FD) or control diet (CD) at six weeks of age. Mice were maintained on these diets for six months, after which animals were euthanized and brain tissue and serum were collected for analysis. Serum folate levels were measured. In brain tissue, hippocampal volume and morphology including Cornu Ammonis 1 and 3 (CA1; CA3), and dentate gyrus thickness were measured. Apoptosis within the hippocampus was assessed using active caspase-3 immunofluorescence staining. Additionally, cortical acetylcholine metabolism was measured in brain tissue using immunofluorescence staining of acetylcholinesterase (AChE), or choline acetyltransferase (ChAT), and neuronal nuclei (NeuN).

Results

Male and female FD mice had reduced serum levels of folate. Both males and females maintained on a FD showed a decrease in the thickness of the hippocampal CA1-CA3 region. Interestingly, there was a sex difference in the levels of active caspase-3 within the CA3 region of the hippocampus. In cortical tissue, there were increased levels of neuronal ChAT and reduced levels of AChE in FD females and male mice.

Conclusions

The results indicated that FD impacts hippocampal morphology and cortical neuronal acetylcholine metabolism. The data from our study indicate that there was only one sex difference and that was in hippocampal apoptosis. Our study provides little evidence that sex modulates the effects of dietary folate deficiency on hippocampal morphology and cortical neuronal acetylcholine metabolism.
Evolutionary rescue can prevent rate-induced tipping
Authors: Vanselow Anna , Halekotte Lukas , Feudel Ulrike
Published: December 2020

Today, the transformation of ecosystems proceeds at unprecedented rates. Recent studies suggest that high rates of environmental change can causerate-induced tipping. In ecological models, the associatedrate-induced critical transitionmanifests during transient dynamics in which populations drop to dangerously low densities. In this work, we study howindirect evolutionary rescue- due to the rapid evolution of a predator’s trait - can save a prey population from the rate-induced collapse. Therefore, we explicitly include the time-dependent dynamics of environmental change and evolutionary adaptation in an eco-evolutionary system. We then examine how fast the evolutionary adaptation needs to be to counteract the response to environmental degradation and express this relationship by means of a critical rate. Based on this critical rate, we conclude that indirect evolutionary rescue is more probable if the predator population possesses a high genetic variation and, simultaneously, the environmental change is slow. Hence, our results strongly emphasize that the maintenance of biodiversity requires a deceleration of the anthropogenic degradation of natural habitats.
Plasticity of fibroblast transcriptional response to physical and biochemical cues revealed by dynamic network analysis
Authors: Lee Pilhwa , Decker Joseph , Shea Lonnie , Beard Daniel A.
Published: December 2020

Data on human skin fibroblast transcriptional responses to external cues were used to reconstruct dynamic gene regulatory networks. The goal of the reconstruction was to determine dynamic network interactions (quantitative predictive relationships of mutual regulatory influences of and on transcription factor expression) from time course data on 56 transcript expression levels obtained following different external cues. The inherently under-determined nature of this problem was addressed in part by excluding putative regulatory motifs that did not appear to be functional in multiple independent experiments from different independent external perturbations. Data were obtained from a previously published experiment in which the 56 transcripts were assayed by bioluminescence in live cells cultured on substrates of varying levels of stiffness and exposed to different levels of arginylglycylaspartic acid (RGD) peptide. The inferred dynamical networks were validated via comparison of predictions toa prioriknown interactions from gene databases. We discovered that exposures to different substrate stiffnesses and to RGD stimulate responses that are mediated throughGATA4, SMAD3/4, ETS-1, andSTAT5and other genes, which can initiate hypertrophic, fibrotic, and inflammatory responses. The developed dynamical system identification method for discovering new mechanotransduction pathways is applicable to the identification of gene regulatory networks in numerous emerging applications where time-series data on multiple state variables and from multiple external perturbations are available.
Surveying the contribution of rare variants to the genetic architecture of human disease through exome sequencing of 177,882 UK Biobank participants
Authors: Wang Quanli , Dhindsa Ryan S. , Carss Keren , Harper Andrew , Nag Abhishek , Tachmazidou Ioanna , Vitsios Dimitrios , Deevi Sri VV , Mackay Alex , Muthas Daniel , Hühn Michael , Monkley Susan , Olsson Henric , Wasilewski Sebastian , Smith Katherine R. , March Ruth , Platt Adam , Haefliger Carolina , Petrovski Slavé ,   AstraZeneca Genomics Initiative
Published: December 2020

The UK Biobank (UKB) represents an unprecedented population-based study of 502,543 participants with detailed phenotypic data and linkage to medical records. While the release of genotyping array data for this cohort has bolstered genomic discovery for common variants, the contribution of rare variants to this broad phenotype collection remains relatively unknown. Here, we use exome sequencing data from 177,882 UKB participants to evaluate the association between rare protein-coding variants with 10,533 binary and 1,419 quantitative phenotypes. We performed both a variant-level phenome-wide association study (PheWAS) and a gene-level collapsing analysis-based PheWAS tailored to detecting the aggregate contribution of rare variants. The latter revealed 911 statistically significant gene-phenotype relationships, with a median odds ratio of 15.7 for binary traits. Among the binary trait associations identified using collapsing analysis, 83% were undetectable using single variant association tests, emphasizing the power of collapsing analysis to detect signal in the setting of high allelic heterogeneity. As a whole, these genotype-phenotype associations were significantly enriched for loss-of-function mediated traits and currently approved drug targets. Using these results, we summarise the contribution of rare variants to common diseases in the context of the UKB phenome and provide an example of how novel gene-phenotype associations can aid in therapeutic target prioritisation.
Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment
Authors: Ko J. , Meyer A. N. , Haas M. , Donoghue D. J.
Published: December 2020

Background

Metastatic castrate-resistant prostate cancer (CRPC) remains uncurable and novel therapies are needed to better treat patients. Aberrant Fibroblast Growth Factor Receptor (FGFR) signaling has been implicated in advanced prostate cancer (PCa), and FGFR1 is suggested to be a promising therapeutic target along with current androgen deprivation therapy.

Methods

We established a novelin vitro3D culture system to study endogenous FGFR signaling in a rare subpopulation of prostate cancer stem cells (CSCs) in the cell lines PC3, DU145, LNCaP, and the induced pluripotent iPS87 cell line.

Results

3D-propagation of PCa cells generated spheroids with increased stemness markers ALDH7A1 and OCT4, while inhibition of FGFR signaling by BGJ398 or Dovitinib decreased cell survival and proliferation of 3D spheroids. The 3D spheroids exhibited altered expression of EMT markers associated with metastasis such as E-cadherin, vimentin and Snail, compared to 2D monolayer cells. TKI treatment did not result in significant changes of EMT markers, however, specific inhibition of FGFR signaling by BGJ398 showed more favorable molecular-level changes than treatment with the multi-RTK inhibitor Dovitinib.

Conclusions

This study provides evidence for the first time that FGFR1 plays an essential role in the proliferation of PCa CSCs at a molecular and cellular level, and suggests that TKI targeting of FGFR signaling may be a promising strategy for AR-independent CRPC.
A New and Improved Genome Sequence ofCannabis sativa
Authors: Braich Shivraj , Baillie Rebecca C. , Spangenberg German C. , Cogan Noel O.I.
Published: December 2020

Cannabis is a diploid species (2n = 20), the estimated haploid genome sizes of the female and male plants using flow cytometry are 818 and 843 Mb respectively. Although the genome of Cannabis has been sequenced (from hemp, wild and high-THC strains), all assemblies have significant gaps. In addition, there are inconsistencies in the chromosome numbering which limits their use. A new comprehensive draft genome sequence assembly (~900 Mb) has been generated from the medicinal cannabis strain Cannbio-2, that produces a balanced ratio of cannabidiol and delta-9-tetrahydrocannabinol using long-read sequencing. The assembly was subsequently analysed for completeness by ordering the contigs into chromosome-scale pseudomolecules using a reference genome assembly approach, annotated and compared to other existing reference genome assemblies. The Cannbio-2 genome sequence assembly was found to be the most complete genome sequence available based on nucleotides assembled and BUSCO evaluation inCannabis sativawith a comprehensive genome annotation. The new draft genome sequence is an advancement in Cannabis genomics permitting pan-genome analysis, genomic selection as well as genome editing.
Expression of SSEA4 and TRA1-60 as Marker of Induced Pluripotent Stem Cells by Small Molecule Compound VC6TFZ on Peripheral Blood Mononuclear Cell
Authors: Andrianto A , Basworo Adityo , Dewi Ivana Purnama , Pikir Budi Susetio
Published: December 2020

Introduction

It is possible to induce pluripotent stem cells from somatic cells, offering an infinite cell resource with the potential for disease research and use in regenerative medicine. Due to ease of accessibility, minimum invasive treatment, and can be kept frozen, peripheral blood mononuclear cells (PBMC) were an attractive source cell. VC6TFZ, a small molecule compound, has been successfully reprogrammed from mouse fibroblast induced pluripotent stem cells (iPSCs). However, it has not been confirmed in humans.

Objective

The aim of this research is to determine whether the small molecule compound VC6TFZ can induced pluripotency of PBMC to generate iPSCs detected with expression of SSEA4 and TRA1-60.

Methods

Using the centrifugation gradient density process, mononuclear cells were separated from peripheral venous blood. Mononuclear cells were cultured for 6 days in the expansion medium. The cells were divided into four groups; group 1 (P1), which was not exposed to small molecules (control group) and groups 2-4 (P2-P4), the experimental groups, subjected to various dosages of the small molecule compound VC6TFZ (VPA, CHIR, Tranylcypromine, FSK, Dznep, and TTNPB). The induction of pluripotency using small molecule compound VC6TFZ was completed within 14 days, then for 7 days the medium shifted to 2i medium. iPSCs identification in based on colony morphology and pluripotent gene expression, SSEA4 and TRA1-60 marker, using immunocytochemistry.

Results

Colonies appeared on reprogramming process in day 7th. These colonies had round, large, and cobble stone morphology like ESC. Gene expression of SSEA4 and TRA 1-60 increased statisticaly significant than control group (SSEA4 were P2 p=0.007; P3 p=0.001; P4 p=0.009 and TRA 1-60 were P2 p=0.002; P3 p=0.001; P4 p=0.001).

Conclusion

Small molecule compound VC6TFZ could induced pluripotency of human PBMC to generate iPSCs. Pluripotxency marker gene expression, SSEA 4 and TRA 1-60, in the experimental group was statistically significantly higher than in the control group.
Functional Transcriptome Analysis of Bladder Cancer Cell Lines Persistently Infected with Oncolytic Newcastle Disease Virus
Authors: Ahmad Umar , Thirumorthy Arcana , Chau De Ming , Chia Suet Lin , Yusoff Khatijah , Abdullah Syahril , Chan Soon Choy , Veerakumarasivam Abhi
Published: December 2020

Background

Newcastle disease virus (NDV) has been an attractive virotherapy agent that targets various type of human cancers while leaving normal cells unharmed. Wild-type NDV strain AF2240 has been found to persistently infect subpopulation of cancer cellsin vitro, making the cells less susceptible to NDV-mediated oncolysis. It is proposed that transcriptome profiling of NDV persistently infected bladder cancer cell lines will provide insights to understand such occurrence by identifying specific pathways associated with NDV persistent infection due to transcriptomic dysregulation.

Results

Transcriptome profiling revealed a total of 63 and 134 differentially expressed genes (DEGs) from NDV persistently infected TCCSUPPi and EJ28Pi bladder cancer cells relative to their uninfected controls, respectively. Of the 63 DEGs identified for TCCSUPPi cells, 25 DEGs were upregulated (log2fold-change ≥ 0) and 38 DEGs were downregulated (log2fold-change ≤ 0). These genes were significantly enriched in the molecular function of calcium binding (GO:0005509) and DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227) and the enriched important upregulated pathways were mainly heme metabolism, TGF-beta signaling and spermatogenesis. As for EJ28Pi, 55 DEGs were upregulated (log2fold-change ≥ 0) and 79 DEGs were downregulated (log2fold-change ≤ 0). These DEGs resulted in significantly enriched molecular function such as protein domain specific binding (GO:0019904) and RNA polymerase II regulatory region sequence-specific DNA binding (GO:0000977). The enriched important upregulated pathways were allograft rejection, KRAS signaling up and interferon gamma response. Other important pathways that were downregulated in both the NDV-persistently infected cell lines were angiogenesis, apoptosis, and xenobiotic metabolism.

Conclusion

The transcriptome profiles (RNA-Seq) of these cell lines suggest that evasion of apoptosis and increase in TGF-beta signaling and interferon gamma response activities are crucial for establishment of NDV persistent infection in bladder cancer cells. Findings from this study provide the molecular basis that warrant further study on how bladder cancer cells acquired NDV persistent infection. Resolving the mechanism of persistent infection will facilitate the application of NDV for more effective treatment of bladder cancer.
Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors
Authors: Lin Li , Zhou Ning , Kang Le , Wang Qi , Wu Jian , Wang Xiaoyan , Yang Chunjie , Zhang Guoping , Chen Yunqin , Jiang Hong , Chen Ruizhen , Yang Xiangdong , Sun Aijun , Gong Hui , Ren Jun , Aikawa Hiroshi , Issei Komuro , Ge Junbo , Yang Cheng , Zou Yunzeng
Published: December 2020

Oxidized low-density lipoprotein (Ox-LDL) can induce cardiac hypertrophy, but the mechanism is still unclear. Here we elucidate the role of angiotensin II (AngII) receptor (AT1-R) in Ox-LDL-induced cardiomycyte hypertrophy. Inhibition of Ox-LDL receptor LOX-1 and AT1-R rather than AngII abolished Ox-LDL-induced hypertrophic responses. Similar results were obtained from the heart of mice lacking endogenous Ang II and their cardiomyocytes. Ox-LDL but not AngII induced binding of LOX-1 to AT1-R, and the inhibition of LOX-1 or AT1-R rather than AngII abolished the association of these two receptors. Ox-LDL-induced ERKs phosphorylation in LOX-1 and AT1-R-overexpression cells and the binding of both receptors were suppressed by the mutants of LOX-1 (Lys266Ala/Lys267Ala) or AT1-R (Glu257Ala), however, the AT1-R mutant lacking Gq protein-coupling ability only abolished the ERKs phosphorylation. The phosphorylation of ERKs induced by Ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by Gq protein inhibitor but not by Jak2, Rac1 and RhoA inhibitors. Therefore, the direct interaction between LOX-1 and AT1-R and the downstream Gq protein activation are important mechanisms for Ox-LDL-but not AngII-induced cardiomyocyte hypertrophy.
60 fs, 1030 nm FEL pump–probe laser based on a multi-pass post-compressed Yb:YAG source
Authors: Viotti Anne-Lise , Alisauskas Skirmantas , Bin Wahid Ammar , Balla Prannay , Schirmel Nora , Manschwetus Bastian , Hartl Ingmar , Heyl Christoph M.
Published: December 2020

This paper reports on nonlinear spectral broadening of 1.1 ps pulses in a gas-filled multi-pass cell to generate sub-100 fs optical pulses at 1030 nm and 515 nm at pulse energies of 0.8 mJ and 225 µJ, respectively, for pump–probe experiments at the free-electron laser FLASH. Combining a 100 kHz Yb:YAG laser with 180 W in-burst average power and a post-compression platform enables reaching simultaneously high average powers and short pulse durations for high-repetition-rate FEL pump–probe experiments.
Turbojet direct-thrust control scheme for full-envelope fuel consumption minimization
Authors: Villarreal-Valderrama Francisco , Santana Delgado Carlos , Zambrano-Robledo Patricia Del Carmen , Amezquita-Brooks Luis
Published: December 2020

Purpose

Reducing fuel consumption of unmanned aerial vehicles (UAVs) during transient operation is a cornerstone to achieve environment-friendly operations. The purpose of this paper is to develop a control scheme that improves the fuel economy of a turbojet in its full operating envelope.

Design/methodology/approach

A novel direct-thrust linear quadratic integral (LQI) approach, comprised by an optimal observer/controller satisfying specified performance parameters, is presented. The thrust estimator, based in a Wiener model, is validated with the experimental data of a micro-turbojet. Model uncertainty is characterized by analyzing variations between the identified model and measured data. The resulting uncertainty range is used to verify closed-loop stability with the circle criterion. The proposed controller provides stable responses with the specified performance in the whole operating range, even with after considering plant nonlinearities. Finally, the direct-thrust LQI is compared with a standard thrust controller to assess fuel economy and performance.

Findings

The direct-thrust LQI approach reduced the fuel consumption by 2.1090% in the most realistic scenario. The controllers were also evaluated using the environmental effect parameter (EEP) and transient-thrust-specific fuel consumption (T-TSFC). These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy. Controllers were also evaluated using the EEP and T-TSFC. These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy.

Originality/value

This study shows the design of an effective direct-thrust control approach that minimizes fuel consumption, ensures stable responses for the full operation range, allows isolating the thrust dynamics when designing the controller and is compatible with classical robustness and performance metrics. Finally, the study shows that a simple controller can reduce the fuel consumption of the turbojet during transient operation in scenarios that approximate realistic operating conditions.
Birla 3M Limited
Authors: Sriram M S
Published: December 2020

The case deals with the concepts relating to finalization of accounts using basic data on transactions. It is expected that income statement, balance sheet and adjusting will be passed with the help of information given within the case.
A novel addressing algorithm of radix-2 FFT using single-bank dual-port memory
Authors: Kaya Zeynep , Seke Erol
Published: December 2020

Purpose

This paper aims to present a single-block memory-based FFT processor design with a conflict-free addressing scheme for field-programmable gate arrays FPGAs with dual-port block memories. This study aims for a single-block dual-port memory-based N-point radix-2 FFT design that uses memory locations and spending minimum clock cycle.

Design/methodology/approach

A new memory-based Fast Fourier Transform (FFT) design that uses a dual-port memory block is proposed. Dual-port memory allows the design to perform two memory reads and writes in a single clock cycle. This approach achieves low operational clock and smallest memory simultaneously, excluding some small overhead for exceptional address changes. The methodology is to read from while writing to a memory location, eliminating the need for excess memory and additional clock cycles.

Findings

With the minimum memory size and the simplest architecture, radix-2 FFT and single-memory block are used. The number of clock pulses spent for all FFT operations does not provide much advantage for low-point FFT operations but is important for high-point FFT operations. With the developed algorithm, N memory is used, and the number of clock pulses spent for all FFT stages is (N/2 +1)log2N for all FFT operations.

Originality/value

This is an original paper, which has simultaneously in whole or in part been submitted anywhere else.
Structural equation modeling and artificial neural networks approach to predict continued use of mobile taxi booking apps: the mediating role of hedonic motivation
Authors: Siyal Abdul Waheed , Chen Hongzhuan , Chen Gang , Memon Muhammad Mujahid , Binte Zainab
Published: December 2020

Purpose

Mobile taxi booking apps (MTB) have revolutionalized the transportation industry. As taxis can be hired via smartphones, irrespective of any time or place, the business platform for taxi service has completely changed. Now customers are saved from the hassle of going to the designated taxi stands or waiting along the roadside. But, the long-term sustainability of this service depends on its continued use. Therefore, this study aims to explore factors that hedonically incline people toward continuance of MTB. To achieve the purpose, the unified theory of acceptance and use of technology (UTAUT) was extended with mediation effects of hedonic motivation.

Design/methodology/approach

The data were collected from existing users of MTB and analyzed through structural equation modeling and revalidated via artificial neural networks.

Findings

The statistical results show that the main factors of UTAUT substantially create hedonic motivation to use the apps and significantly mediate their effects on behavioral intention to continue using MTB. However, mediation between social influence and continuity intent was not statistically supported. The findings represent important contributions to the extended UTAUT.

Practical implications

This study adds value to the theoretical horizon and also presents M-taxi companies with useful and pertinent plans for efficient designing and effective implementation of MTB. Moreover, limitations and suggestions for future researchers are also discussed.

Originality/value

This study extends UTAUT with the mediating role of hedonic motivation to predict continued use of MTB, which further initiates the applicability of UTAUT in a new setting and a new perspective (post adoption). This, in turn, significantly expands theory by using hedonic motivation as an important attribute that could mediate impact of all main antecedents to shape customers loyalty toward system use.
A hybrid finite volume/finite element method for shallow water waves by static deformation on seabeds
Authors: Al-Ghosoun Alia , Osman Ashraf S. , Seaid Mohammed
Published: December 2020

Purpose

The purpose of this study is twofold: first, to derive a consistent model free-surface runup flow problems over deformable beds. The authors couple the nonlinear one-dimensional shallow water equations, including friction terms for the water free-surface and the two-dimensional second-order solid elastostatic equations for the bed deformation. Second, to develop a robust hybrid finite element/finite volume method for solving free-surface runup flow problems over deformable beds. The authors combine the finite volume for free-surface flows and the finite element method for bed elasticity.

Design/methodology/approach

The authors propose a new model for wave runup by static deformation on seabeds. The model consists of the depth-averaged shallow water system for the water free-surface coupled to the second-order elastostatic formulation for the bed deformation. At the interface between the water flow and the seabed, transfer conditions are implemented. Here, hydrostatic pressure and friction forces are considered for the elastostatic equations, whereas bathymetric forces are accounted for in the shallow water equations. As numerical solvers, the authors propose a well-balanced finite volume method for the flow system and a stabilized finite element method for elastostatics.

Findings

The developed coupled depth-averaged shallow water system and second-order solid elastostatic system is well suited for modeling wave runup by deformation on seabeds. The derived coupling conditions at the interface between the water flow and the bed topography resolve well the condition transfer between the two systems. The proposed hybrid finite volume element method is accurate and efficient for this class of models. The novel technique used for wet/dry treatment accurately captures the moving fronts in the computational domain without generating nonphysical oscillations. The presented numerical results demonstrate the high performance of the proposed methods.

Originality/value

Enhancing modeling and computations for wave runup problems is at an early stage in the literature, and it is a new and exciting area of research. To the best of our knowledge, solving wave runup problems by static deformation on seabeds using a hybrid finite volume element method is presented for the first time. The results of this research study, and the research methodologies, will have an important influence on a range of other scientists carrying out research in related fields.
Effects of rectors’ narcissism on academics’ silence and commitment in the context of public universities
Authors: Mousa Mohamed , Chaouali Walid , Aboramadan Mohammed , Ayoubi Rami , Abdelgaffar Hala
Published: December 2020

Purpose

This paper aims to focus on academics’ in four public universities located in Egypt to explore the effect of narcissistic leadership on affective, continuance and normative commitment approaches with and without the mediating effect of academics’ silence.

Design/methodology/approach

The authors used a convenience sampling in which academics were handed a questionnaire form to fill. In total, the authors distributed 280 forms and collected 214 completed questionnaire forms. A structural equation was used to determine the effect of narcissistic leadership on the organizational commitment (affective, continuance and normative) of academics. The same measure was later used to assess the mediating role of the academics’ silence on the aforementioned relationship.

Findings

The authors of this paper found that narcissistic leadership positively associates with academics’ silence. Moreover, their perceptions of the narcissism of their leaders alleviate academics’ emotional attachments (affective commitment) and moral obligations (normative commitment) toward their universities, whereas the same perceptions of the narcissism of their leaders have no effect on their continuance commitment. Finally, the authors discovered a significant role for academics’ silence in mediating the negative relationship between narcissistic leadership and their affective and normative commitments.

Originality/value

This paper contributes by filling a gap in leadership, HR management and organization literature in the higher education sector, in which empirical studies on the relationship between narcissistic leadership, academics’ silence and organizational commitment have been limited until now.