Pathogenicity island cag, vacA and IS605 genotypes in Mexican strains of Helicobacter pylori associated with peptic ulcers

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is associated with chronic gastritis, peptic ulcers, and gastric cancer. Two major virulence factors of <it>H. pylori </it>have been described: the pathogenicity island <it>cag </it>(<it>cag </it>PAI) and the vacuolating cytotoxin gene (<it>vacA</it>). Virtually all strains have a copy of <it>vacA</it>, but its genotype varies. The <it>cag </it>PAI is a region of 32 genes in which the insertion of IS<it>605 </it>elements in its middle region has been associated with partial or total deletions of it that have generated strains with varying virulence. Accordingly, the aim of this work was to determine the <it>cag </it>PAI integrity<it>, vacA </it>genotype and IS<it>605 </it>status in groups of isolates from Mexican patients with non-peptic ulcers (NPU), non-bleeding peptic ulcers (NBPU), and bleeding peptic ulcers (BPU).</p> <p>Methods</p> <p>The <it>cag </it>PAI integrity was performed by detection of eleven targeted genes along this locus using dot blot hybridization and PCR assays. The <it>vacA </it>allelic, <it>cag </it>PAI genotype 1 and IS<it>605 </it>status were determined by PCR analysis.</p> <p>Results</p> <p>Groups of 16-17 isolates (n = 50) from two patients with NPU, NBPU, and BPU, respectively, were studied. 90% (45/50) of the isolates harbored a complete <it>cag </it>PAI. Three BPU isolates lacked the <it>cag </it>PAI, and two of the NBPU had an incomplete <it>cag </it>PAI: the first isolate was negative for three of its genes, including deletion of the <it>cagA </it>gene, whereas the second did not have the <it>cagM </it>gene. Most of the strains (76%) had the <it>vacA </it>s1b/m1 genotype; meanwhile the IS<it>605 </it>was not present within the <it>cag </it>PAI of any strain but was detected elsewhere in the genome of 8% (4/50).</p> <p>Conclusion</p> <p>The patients had highly virulent strains since the most of them possessed a complete <it>cag </it>PAI and had a <it>vacA </it>s1b/m1 genotype. All the isolates presented the <it>cag </it>PAI without any IS<it>605 </it>insertion (genotype 1). Combined <it>vacA </it>genotypes showed that 1 NPU, 2 NBPU, and 1 BPU patients (66.6%) had a mixed infection; coexistence of <it>H. pylori </it>strains with different <it>cag </it>PAI status was observed in 1 NBPU and 2 BPU (50%) of the patients, but only two of these patients (NBPU and BPU) had different <it>vacA </it>genotypes.</p

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A Simulation Analysis of an Influenza Vaccine Production Plant in Areas of High Humanitarian Flow. A Preliminary Study for the Region of Norte de Santander (Colombia)

The production of vaccines of biological origin presents a tremendous challenge for researchers. In this context, animal cell cultures are an excellent alternative for the isolation and production of biologicals against several viruses, since they have an affinity with viruses and a great capacity for their replicability. Different variables have been studied to know the system&rsquo;s ideal parameters, allowing it to obtain profitable and competitive products. Consequently, this work focuses its efforts on evaluating an alternative for producing an anti-influenza biological from MDCK cells using SuperPro Designer v8.0 software. The process uses the DMEN culture medium supplemented with nutrients as raw material for cell development; the MDCK cells were obtained from a potential scale-up with a final working volume of 500 L, four days of residence time, inoculum volume of 10%, and continuous working mode with up to a total of 7400 h/Yr of work. The scheme has the necessary equipment for the vaccine&rsquo;s production, infection, and manufacture with yields of up to 416,698 units/h. In addition, it was estimated to be economically viable to produce recombinant vaccines with competitive prices of up to 0.31 USD/unit

Enhancement of Metabolite Production in High-Altitude Microalgal Strains by Optimized C/N/P Ratio

This study evaluated the role of C/N/P in the increase in the synthesis of carbohydrates, proteins, and lipids in two high-mountain strains of algae (Chlorella sp. UFPS019 and Desmodesmus sp. UFPS021). Three carbon sources (sodium acetate, sodium carbonate, and sodium bicarbonate), and the sources of nitrogen (NaNO3) and phosphate (KH2PO4 and K2HPO4) were analyzed using a surface response (3 factors, 2 levels). In Chlorella sp. UFPS019, the optimal conditions to enhance the synthesis of carbohydrates were high sodium carbonate content (3.53 g/L), high KH2PO4 and K2HPO4 content (0.06 and 0.14 g/L, respectively), and medium-high NaNO3 (0.1875 g/L). In the case of lipids, a high concentration of sodium acetate (1.19 g/L) coupled with high KH2PO4 and K2HPO4 content (0.056 and 0.131 g/L, respectively) and a low concentration of NaNO3 (0.075 g/L) drastically induced the synthesis of lipids. In the case of Desmodesmus sp. UFPS021, the protein content was increased using high sodium acetate (2 g/L), high KH2PO4 and K2HPO4 content (0.056 and 0.131 g/L, respectively), and high NaNO3 concentration (0.25 g/L). These results demonstrate that the correct adjustment of the C/N/P ratio can enhance the capacity of high-mountain strains of algae to produce high concentrations of carbohydrates, proteins, and lipids

Enhancement of Metabolite Production in High-Altitude Microalgal Strains by Optimized C/N/P Ratio

This study evaluated the role of C/N/P in the increase in the synthesis of carbohydrates, proteins, and lipids in two high-mountain strains of algae (Chlorella sp. UFPS019 and Desmodesmus sp. UFPS021). Three carbon sources (sodium acetate, sodium carbonate, and sodium bicarbonate), and the sources of nitrogen (NaNO3) and phosphate (KH2PO4 and K2HPO4) were analyzed using a surface response (3 factors, 2 levels). In Chlorella sp. UFPS019, the optimal conditions to enhance the synthesis of carbohydrates were high sodium carbonate content (3.53 g/L), high KH2PO4 and K2HPO4 content (0.06 and 0.14 g/L, respectively), and medium-high NaNO3 (0.1875 g/L). In the case of lipids, a high concentration of sodium acetate (1.19 g/L) coupled with high KH2PO4 and K2HPO4 content (0.056 and 0.131 g/L, respectively) and a low concentration of NaNO3 (0.075 g/L) drastically induced the synthesis of lipids. In the case of Desmodesmus sp. UFPS021, the protein content was increased using high sodium acetate (2 g/L), high KH2PO4 and K2HPO4 content (0.056 and 0.131 g/L, respectively), and high NaNO3 concentration (0.25 g/L). These results demonstrate that the correct adjustment of the C/N/P ratio can enhance the capacity of high-mountain strains of algae to produce high concentrations of carbohydrates, proteins, and lipids

Application of <i>Chlorella</i> sp. and <i>Scenedesmus</i> sp. in the Bioconversion of Urban Leachates into Industrially Relevant Metabolites

This paper explores the ability of Chlorella sp. and Scenedesmus sp. to convert landfill leachates into usable metabolites. Different concentrations (0.5, 1, 5, and 10% v/v) of leachate coupled with an inorganic carbon source (Na2CO3, and NaHCO3) were tested to improve biomass production, metabolites synthesis, and removal of NO3 and PO4. The result shows that both strains can effectively grow in media with up to 5% (v/v) leachate, while significantly reducing the concentrations of NO3, and PO4 (80 and 50%, respectively). The addition of NaHCO3 as a carbon source improved the final concentration of biomass, lipids, carbohydrates, and the removal of NO3 and PO4 in both strains

A Simulation Analysis of a Microalgal-Production Plant for the Transformation of Inland-Fisheries Wastewater in Sustainable Feed

The present research evaluates the simulation of a system for transforming inland-fisheries wastewater into sustainable fish feed using Designer&reg; software. The data required were obtained from the experimental cultivation of Chlorella sp. in wastewater supplemented with N and P. According to the results, it is possible to produce up to 11,875 kg/year (31.3 kg/d) with a production cost of up to 18 (USD/kg) for dry biomass and 0.19 (USD/bottle) for concentrated biomass. Similarly, it was possible to establish the kinetics of growth of substrate-dependent biomass with a maximum production of 1.25 g/L after 15 days and 98% removal of available N coupled with 20% of P. It is essential to note the final production efficiency may vary depending on uncontrollable variables such as climate and quality of wastewater, among others

A Simulation Analysis of a Microalgal-Production Plant for the Transformation of Inland-Fisheries Wastewater in Sustainable Feed

The present research evaluates the simulation of a system for transforming inland-fisheries wastewater into sustainable fish feed using Designer® software. The data required were obtained from the experimental cultivation of Chlorella sp. in wastewater supplemented with N and P. According to the results, it is possible to produce up to 11,875 kg/year (31.3 kg/d) with a production cost of up to 18 (USD/kg) for dry biomass and 0.19 (USD/bottle) for concentrated biomass. Similarly, it was possible to establish the kinetics of growth of substrate-dependent biomass with a maximum production of 1.25 g/L after 15 days and 98% removal of available N coupled with 20% of P. It is essential to note the final production efficiency may vary depending on uncontrollable variables such as climate and quality of wastewater, among others