cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.25451749.v1
title: Recombination analysis raw data

description: This research delves into the understanding of the formation of recombinant forms between HIV-1 and HIV-2. Since both HIV-1 and HIV-2 infect the same cell type, they can certainly reside in the same cell and undergo recombination. Recombination between HIV-1 and HIV-2 might have important ramifications for the disease progression phenotype observed in HIV-1 and HIV-2 co-infected individuals. We developed a bioinformatics analysis pipeline which performs an in-depth analysis of recombination to detect these recombinant forms. We found HIV-1/HIV-2 recombinants in circulation based on our analysis. Thus, we conclude that there are HIV-1/HIV-2 recombinants in circulation, and these recombinants are likely to contribute to the observed slow progression of disease in dually infected individuals. Our analysis pipeline is reproducible and can be adopted for the recombination analysis of any retrovirus.
DOI: 10.6084/m9.figshare.21603033.v3
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.21665289.v2
title: Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics

description: Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted “reference isoform” 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.
DOI: 10.34863/25fk-4n21
title: Dataset: The reverse quantum limit and its implications for unconventional quantum oscillations in YbB12
DOI: 10.6084/m9.figshare.21603033.v4
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.21665289.v3
title: Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics

description: Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted “reference isoform” 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.
DOI: 10.6084/m9.figshare.16677619
title: The TCGA cancer data for the paper entitled "Feature Screening for Survival Trait with Application to TCGA High-dimensional Genomic Data"

description: The TCGA ESCA, PAAD, LUAD, and BRCA genomic data with survival traits for the paper entitled "Feature Screening for Survival Trait with Application to TCGA High-dimensional Genomic Data".
DOI: 10.6084/m9.figshare.16677619.v5
title: The TCGA cancer data for the paper entitled "Feature Screening for Survival Trait with Application to TCGA High-dimensional Genomic Data"

description: The TCGA ESCA, PAAD, LUAD, and BRCA genomic data with survival traits for the paper entitled "Feature Screening for Survival Trait with Application to TCGA High-dimensional Genomic Data".
DOI: 10.6084/m9.figshare.21603033.v5
title: Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)<sup>+</sup> RNA foci adjacent to nuclear speckles following activation of ATM (ataxia telangiectasia mutated)

description: Intracellular and intercellular signalling networks play an essential role in optimizing cellular homoeostasis and are thought to be partly reflected in nuclear mRNA dynamics. However, the regulation of nuclear mRNA dynamics by intracellular and intercellular signals remains largely unexplored, and research tools are lacking. Through an original screening based on the mRNA metabolic mechanism, we discovered that eight well-known inhibitors cause significant nuclear poly(A)<sup>+</sup> RNA accumulation. Among these inhibitors, we discovered a new mRNA metabolic response in which the addition of antimycin A, an inhibitor of mitochondrial respiratory-chain complex III (complex III), resulted in a marked accumulation of poly(A)<sup>+</sup> RNA near the nuclear speckles. Furthermore, dihydroorotate dehydrogenase (DHODH) inhibitors, a rate-limiting enzyme in the intracellular <i>de novo</i> pyrimidine synthesis reaction that specifically exchanges electrons with complex III, also caused a remarkable accumulation of nuclear poly(A)<sup>+</sup> RNA adjacent to the nuclear speckles, which was abolished by extracellular uridine supply, indicating that the depletion of intracellular pyrimidine affects poly(A)<sup>+</sup> RNA metabolism. Further analysis revealed that ataxia telangiectasia mutated (ATM), a serine and threonine kinase and a master regulator of DNA double-strand break (DSB) and nucleolar stress, is required for this poly(A)<sup>+</sup> RNA nuclear accumulation phenomenon. This study reports new insights into novel aspects of nuclear poly(A)<sup>+</sup> RNA metabolism, especially the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
DOI: 10.6084/m9.figshare.15050601.v1
title: Establishing an invertebrate <i>Galleria mellonella</i> greater wax moth larval model of <i>Neisseria gonorrhoeae</i> infection

description: <i>Neisseria gonorrhoeae</i> (gonococcus) causes the human sexually transmitted disease gonorrhea. Studying gonococcal pathogenesis and developing new vaccines and therapies to combat the increasing prevalence of multi-antibiotic resistant bacteria has made use of many <i>ex vivo</i> models based on human cells and tissues, and <i>in vivo</i> vertebrate models, for example, rodent, pig and human. The focus of the current study was to examine the utility of the invertebrate greater wax moth <i>Galleria mellonella</i> as an <i>in vivo</i> model of gonococcal infection. We observed that a threshold of ~10<sup>6</sup> – 10<sup>7</sup> gonococci/larva was required to kill &gt;50% of larvae (P &lt; 0.05), and increased toxicity correlated with reduced health index scores and pronounced histopathological changes such as increases in the total lesion grade, melanized nodules, hemocyte reaction, and multifocal adipose body degeneration. Larval death was independent of the expression of pilus or Opa protein or LOS sialylation within a single gonococcal species studied, but the model could demonstrate relative toxicity of different isolates. <i>N. meningitidis, N. lacatamica</i> and gonococci all killed larvae equally, but were significantly less toxic (P &gt; 0.05) than <i>Pseudomonas aeruginosa</i>. Larvae primed with nontoxic doses of gonococci were more susceptible to subsequent challenge with homologous and heterologous bacteria, and larval survival was significantly reduced (P &lt; 0.05) in infected larvae after depletion of their hemocytes with clodronate-liposomes. The model was used to test the anti-gonococcal properties of antibiotics and novel antimicrobials. Ceftriaxone (P &lt; 0.05) protected larvae from infection with different gonococcal isolates, but not azithromycin or monocaprin or ligand-coated silver nanoclusters (P &gt; 0.05).
DOI: 10.6084/m9.figshare.15050601.v2
title: Establishing an invertebrate <i>Galleria mellonella</i> greater wax moth larval model of <i>Neisseria gonorrhoeae</i> infection

description: <i>Neisseria gonorrhoeae</i> (gonococcus) causes the human sexually transmitted disease gonorrhea. Studying gonococcal pathogenesis and developing new vaccines and therapies to combat the increasing prevalence of multi-antibiotic resistant bacteria has made use of many <i>ex vivo</i> models based on human cells and tissues, and <i>in vivo</i> vertebrate models, for example, rodent, pig and human. The focus of the current study was to examine the utility of the invertebrate greater wax moth <i>Galleria mellonella</i> as an <i>in vivo</i> model of gonococcal infection. We observed that a threshold of ~10<sup>6</sup> – 10<sup>7</sup> gonococci/larva was required to kill &gt;50% of larvae (P &lt; 0.05), and increased toxicity correlated with reduced health index scores and pronounced histopathological changes such as increases in the total lesion grade, melanized nodules, hemocyte reaction, and multifocal adipose body degeneration. Larval death was independent of the expression of pilus or Opa protein or LOS sialylation within a single gonococcal species studied, but the model could demonstrate relative toxicity of different isolates. <i>N. meningitidis, N. lacatamica</i> and gonococci all killed larvae equally, but were significantly less toxic (P &gt; 0.05) than <i>Pseudomonas aeruginosa</i>. Larvae primed with nontoxic doses of gonococci were more susceptible to subsequent challenge with homologous and heterologous bacteria, and larval survival was significantly reduced (P &lt; 0.05) in infected larvae after depletion of their hemocytes with clodronate-liposomes. The model was used to test the anti-gonococcal properties of antibiotics and novel antimicrobials. Ceftriaxone (P &lt; 0.05) protected larvae from infection with different gonococcal isolates, but not azithromycin or monocaprin or ligand-coated silver nanoclusters (P &gt; 0.05).
DOI: 10.6084/m9.figshare.17294157.v1
title: The aggregate-forming pili (AFP) mediates the aggregative adherence of a hybrid-pathogenic <i>Escherichia coli</i> (UPEC/EAEC) isolated from a urinary tract infection

description: Enteroaggregative <i>Escherichia coli</i> (EAEC) comprises an important diarrheagenic pathotype, while uropathogenic <i>E. coli</i> (UPEC) is the most important agent of urinary tract infection (UTI). Recently, EAEC virulence factors have been detected in <i>E. coli</i> strains causing UTI, showing the importance of these hybrid-pathogenic strains. Previously, we detected an <i>E. coli</i> strain isolated from UTI (UPEC-46) presenting characteristics of EAEC, <i>e.g</i>., the aggregative adherence (AA) pattern and EAEC-associated genes (<i>aatA, aap</i>, and <i>pet</i>). In this current study, we analyzed the whole genomic sequence of UPEC-46 and characterized some phenotypic traits. The AA phenotype was observed in cell lineages of urinary and intestinal origin. The production of curli, cellulose, bacteriocins, and Pet toxin was detected. Additionally, UPEC-46 was not capable of forming biofilm using different culture media and human urine. The genome sequence analysis showed that this strain belongs to serotype O166:H12, ST10, and phylogroup A, harbors the <i>tet, aadA</i>, and <i>dfrA</i>/<i>sul</i> resistance genes, and is phylogenetically more related to EAEC strains isolated from human feces. UPEC-46 harbors three plasmids. Plasmid p46-1 (~135 kb) carries some EAEC marker genes and those encoding the aggregate-forming pili (AFP) and its regulator (<i>afpR</i>). A mutation in <i>afpA</i> (encoding the AFP major pilin) led to the loss of pilin production and assembly, and notably, a strongly reduced adhesion to epithelial cells. In summary, the genetic background and phenotypic traits analyzed suggest that UPEC-46 is a hybrid strain (UPEC/EAEC) and highlights the importance of AFP adhesin in the adherence to colorectal and bladder cell lines.
DOI: 10.6084/m9.figshare.16602476.v1
title: <i>Helicobacter pylori</i> cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells

description: <i>Helicobacter pylori</i> infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with <i>H. pylori</i> is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. <i>H. pylori</i> cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that <i>H. pylori</i> CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of <i>H. pylori</i> to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of <i>H. pylori</i> CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of <i>H. pylori</i> to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to <i>H. pylori</i> infectivity and it may serve as a key target for the treatment of <i>H. pylori</i>-associated diseases.
DOI: 10.6084/m9.figshare.16586946.v2
title: The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

description: An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates <i>in vitro</i> SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19.
DOI: 10.6084/m9.figshare.14276999.v1
title: PE_PGRS3 ensures provision of the vital phospholipids cardiolipin and phosphatidylinositols by promoting the interaction between <i>M. tuberculosis</i> and host cells

description: PE_PGRS proteins of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) constitute a large family of complex modular proteins whose role is still unclear. Among those, we have previously shown, using the heterologous expression in <i>Mycobacterium smegmatis</i>, that PE_PGRS3 containing a unique arginine-rich C-terminal domain, promotes adhesion to host cells. In this study, we investigate the role of PE_PGRS3 and its C-terminal domain directly in <i>Mtb</i> using functional deletion mutants. The results obtained here show that PE_PGRS3 is localized on the mycobacterial cell wall and its arginine-rich C-terminal region protrudes from the mycobacterial membrane and mediates <i>Mtb</i> entry into epithelial cells. Most importantly, this positively charged helical domain specifically binds phosphorylated phosphatidylinositols and cardiolipin, whereas it is unable to bind other phospholipids. Interestingly, administration of cardiolipin and phosphatidylinositol but no other phospholipids was able to turn-off expression of <i>pe_pgrs</i>3 activated by phosphate starvation conditions. These findings suggest that PE_PGRS3 has the key role to serve as a bridge between mycobacteria and host cells by interacting with specific host phospholipids and extracting them from host cells, for their direct integration or as a source of phosphate, during phases of TB pathogenesis when <i>Mtb</i> is short of phosphate supply.
DOI: 10.6084/m9.figshare.17153057.v1
title: The induced knockdown of GmCAD receptor protein encoding gene in Galleria mellonella decreased the insect susceptibility to a Photorhabdus akhurstii oral toxin

description: <i>Photorhabdus</i> bacteria secrete a repertoire of protein toxins that can kill the host insect. Among them, toxin complex (Tc) proteins have gained significant attention due to their wider conservation across the different bacterial genera. In our laboratory, a C-terminal domain of TcaB protein was characterized from <i>P. akhurstii</i> bacterium that conferred the potent oral insecticidal effect on <i>Galleria mellonella</i>. However, the role of insect gut receptors in the TcaB intoxication process was yet to be investigated. In the current study, we examined the transcription of candidate midgut receptors in TcaB-infected larvae and subsequently cloned a cadherin-like gene, <i>GmCAD</i>, from <i>G. mellonella. GmCAD</i> was highly transcribed in the fourth-instar larval stage and specifically in the midgut tissues. Our ligand blot and binding ELISA assays indicated that TcaB binds to the truncated peptides from the GmCAD transmembrane-proximal region with greater affinity than that from the transmembrane-distal region. Oral administration of bacterially expressed <i>GmCAD</i> dsRNA in <i>G. mellonella</i> severely attenuated the expression of target mRNA, which in turn alleviated the negative effect of TcaB on insect survival (TcaB-induced mortality in CAD dsRNA pretreated larvae reduced by 72–83% compared to control), implying the association of GmCAD in the TcaB intoxication process. Present findings form a basis of future research related to the insect gut receptor interactions with <i>Photorhabdus</i> toxins.