ACE2/ADAM17/TMPRSS2 interplay may be the main risk factor for COVID-19

The Coronavirus Disease 2019 (COVID-19) has already caused hundreds of thousands of deaths worldwide in a few months. Cardiovascular disease, hypertension, diabetes and chronic lung disease have been identified as the main COVID-19 comorbidities. Moreover, despite similar infection rates between men and women, the most severe course of the disease is higher in elderly and co-morbid male patients. Therefore, the occurrence of specific comorbidities associated with renin–angiotensin system (RAS) imbalance mediated by the interaction between angiotensin-converting enzyme 2 (ACE2) and desintegrin and metalloproteinase domain 17 (ADAM17), along with specific genetic factors mainly associated with type II transmembrane serine protease (TMPRSS2) expression, could be decisive for the clinical outcome of COVID-19. Indeed, the exacerbated ADAM17—mediated ACE2, TNF-α, and IL-6R secretion emerges as a possible underlying mechanism for the acute inflammatory immune response and the activation of the coagulation cascade. Therefore, in this review, we focus on the main pathophysiological aspects of ACE2, ADAM17, and TMPRSS2 host proteins in COVID-19. Additionally, we discuss a possible mechanism to explain the deleterious effect of ADAM17 and TMPRSS2 over-activation in the COVID-19 outcome

Integration of Trypanosoma cruzi kDNA minicircle sequence in the host genome may be associated with autoimmune serum factors in chagas disease patients

ABSTRACT: Integration of kDNA sequences within the genome of the host cell shown by PCR amplification with primers to the conserved Trypanosoma cruzi kDNA minicircle sequence was confirmed by Southern hybridization with specific probes. The cells containing the integrated kDNA sequences were then perpetuated as transfected macrophage subclonal lines. The kDNA transfected macrophages expressed membrane antigens that were recognized by antibodies in a panel of sera from ten patients with chronic Chagas disease. These antigens barely expressed in the membrane of uninfected, control macrophage clonal lines were recognized neither by factors in the control, non-chagasic subjects nor in the chagasic sera. This finding suggests the presence of an autoimmune antibody in the chagasic sera that recognizes auto-antigens in the membrane of T. cruzi kDNA transfected macrophage subclonal lines

Determination of triglycerides in Caenorhabditis elegans fed lactobacilli

Caenorhabditis (C.) elegans is regarded as a simple model to assess the in vivo effects of probiotics, especially concerning the study of fat metabolism due to its ability to store lipids in intestinal and skin-like hypodermal cells. The main constituents in fat droplets stored in this nematode are triglycerides (TG). The objective of this work was to evaluate TG levels in C. elegans feeding with lactobacilli alone or combined in different proportions. The strains used in this study are listed as follow: Lacticaseibacillus rhamnosus CRL1425, Lactiplantibacillus plantarum CRL1427, CRL1428, CRL1449, CRL1472, Lacticaseibacillus casei CRL1430, Limosilactobacillus fermentum CRL1446 y Lactobacillus delbrueckii subsp. bulgaricus CRL1447. The strains to the different mix were selected based on previous studied functional properties and were combined as follows: mixture 1 (Mix 1) was formed by CRL1446, CRL1449, and CRL1472; Mixture 2 (Mix 2) by CRL1446 and CRL1449, Mixture 3 (Mix 3) by CRL1446 and CRL1472, and Mixture 4 (Mix 4) by CRL1449 and CRL1472. Nematodes synchronized were fed Escherichia (E.) coli OP50 (controls nematodes) and OP50:Lactobacilli in a ratio of 0:100; 25:75; and 50:50 (nematodes treated) at 18 °C until they reached the L4/adult stage. Then, a 5% solution of Triton X-100 was added and sonicated. The lipids were solubilized at 90 ° C for 5 min, and the lysate was removed by centrifugation. TG was determined in the supernatant by enzymatic methods. At least 3 biological replicas were used for each or mixtures of strains. The results showed that the nematode development was slower in the 0: 100 OP50:Lactobacilli ratio, while the 50:50 OP50:Lactobacilli ratio was similar to the control. In a 25:75 ratio, all strains, except CRL1427 and CRL1428, showed a significant reduction in TG levels. The CRL1425, CRL1446, and CRL1447 strains hat the highest percentage of TG reduction (75, 70, and 75%, respectively). When the nematodes were fed with Mix 1, Mix2 and Mix3 presented a significantly lower TG content than the control, with a reduction percentage of 56, 49, 42%, respectively. However, no significant differences were observed between these mixes. Mix 4 did not induce any change compared with nematode control. In conclusion, C. elegans can be used as a screening method for strains with the ability to reduce TG content, which reports an anti-obesity effect of these strains.Fil: Márquez, María Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Argañaraz, Federico José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Andrada, Lidia Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Medina, Roxana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Grau, Roberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Gauffin Cano, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaLVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; XVI Annual Meeting of the Argentinean Society for General MicrobiologyMendozaArgentinaSociedad Argentina de Investigación en Bioquímica y Biología MolecularSociedad Argentina de Microbiología Genera

Increased prevalence of unstable HLA-C variants in HIV-1 rapid-progressor patients

HIV-1 infection in the absence of treatment results in progression toward AIDS. Host genetic factors play a role in HIV-1 pathogenesis, but complete knowledge is not yet available. Since less-expressed HLA-C variants are associated with poor HIV-1 control and unstable HLA-C variants are associated with higher HIV-1 infectivity, we investigated whether there was a correlation between the different stages of HIV-1 progression and the presence of specific HLA-C allotypes. HLA-C genotyping was performed using allele-specific PCR by analyzing a treatment-naïve cohort of 96 HIV-1-infected patients from multicentric cohorts in the USA, Canada, and Brazil. HIV-1-positive subjects were classified according to their different disease progression status as progressors (Ps, n = 48), long-term non-progressors (LTNPs, n = 37), and elite controllers (ECs, n = 11). HLA-C variants were classified as stable or unstable according to their binding stability to β2-microglobulin/peptide complex. Our results showed a significant correlation between rapid progression to AIDS and the presence of two or one unstable HLA-C variants (p-value: 0.0078, p-value: 0.0143, respectively). These findings strongly suggest a link between unstable HLA-C variants both at genotype and at allele levels and rapid progression to AIDS. This work provides further insights into the impact of host genetic factors on AIDS progression

Current millennium biotechniques for biomedical research on parasites and host-parasite interactions

The development of biotechnology in the last three decades has generated the feeling that the newest scientific achievements will deliver high standard quality of life through abundance of food and means for successfully combating diseases. Where the new biotechnologies give access to genetic information, there is a common belief that physiological and pathological processes result from subtle modifications of gene expression. Trustfully, modern genetics has produced genetic maps, physical maps and complete nucleotide sequences from 141 viruses, 51 organelles, two eubacteria, one archeon and one eukaryote (Saccharomices cerevisiae). In addition, during the Centennial Commemoration of the Oswaldo Cruz Institute the nearly complete human genome map was proudly announced, whereas the latest Brazilian key stone contribution to science was the publication of the Shillela fastidiosa genomic sequence highlythed on a Nature cover issue. There exists a belief among the populace that further scientific accomplishments will rapidly lead to new drugs and methodological approaches to cure genetic diseases and other incurable ailments. Yet, much evidence has been accumulated, showing that a large information gap exists between the knowledge of genome sequence and our knowledge of genome function. Now that many genome maps are available, people wish to know what are we going to do with them. Certainly, all these scientific accomplishments will shed light on many more secrets of life. Nevertheless, parsimony in the weekly announcements of promising scientific achievements is necessary. We also need many more creative experimental biologists to discover new, as yet un-envisaged biotechnological approaches, and the basic resource needed for carrying out mile stone research necessary for leading us to that "promised land"often proclaimed by the mass media

Hitchhiking Trypanosoma cruzi minicircle DNA affects gene expression in human host cells via LINE-1 retrotransposon

The horizontal transfer of Trypanosoma cruzi mitochondrial minicircle DNA to the genomes of naturally infected humans may play an important role in the pathogenesis of Chagas disease. Minicircle integrations within LINE-1 elements create the potential for foreign DNA mobility within the host genome via the machinery associated with this retrotransposon. Here we document integration of minicircle DNA fragments in clonal human macrophage cell lines and their mobilization over time. The movement of an integration event in a clonal transfected cell line was tracked at three months and three years post-infection. The minicircle sequence integrated into a LINE-1 retrotransposon; one such foreign fragment subsequently relocated to another genomic location in association with associated LINE-1 elements. The p15 locus was altered at three years as a direct effect of minicircle/LINE-1 acquisition, resulting in elimination of p15 mRNA. Here we show for the first time a molecular pathology stemming from mobilization of a kDNA/LINE-1 mutation. These genomic changes and detected transcript variations are consistent with our hypothesis that minicircle integration is a causal component of parasite-independent, autoimmune-driven lesions seen in the heart and other target tissues associated with Chagas disease

The electrochemistry of nanostructured Ni–W alloys

This work reports on the features that Ni–W nanostructured alloys, electrodeposited on carbon steel by different current pulse programs, may present depending on their surface morphology and surface composition. The Ni–W nanostructured coating, with a cauliflower structure, lack of fragility, and high WO3/W surface composition ratio, is a stable electrode to catalyze hydrogen evolution reaction, exceeding bulk and electrodeposited Ni catalytic activity. Also, the nanostructured alloys must have a low WO3/W surface composition ratio for Ni and its oxides to provide protection and improve corrosion resistance in sulfate media.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Optimization of the surface properties of nanostructured Ni–W alloys on steel by a mixed silane layer

Ni–W nanostructured coatings electrodeposited on steel by galvanostatic pulses were functionalized by tetraethoxysilane (TEOS) and octadecyltrichlorosilane (OTS) in a two-step procedure. A silica-rich layer is formed by the reaction of TEOS with the metal coating surface oxides, which allows a further reaction with OTS forming a hydrocarbon-silica outer network. This mixed silane layer provides hydrophobicity and improves the corrosion behavior of the Ni–W surface coatings without modifying their excellent mechanical properties.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Diplomatura Diseño y Gestión de Emprendimientos de Turismo Rural : estrategias de agregado de valor a la producción agropecuaria

Trabajos Finales de Integración y Transferencia, Cohorte Cerro Colorado (Diplomatura Diseño y Gestión de Emprendimientos de Turismo Rural) -- UNC- Facultad de Ciencias Agropecuarias, 2019En esta compilación se presentan una selección de cinco (5) trabajos realizados por los alumnos de la Cohorte de la Diplomatura desarrollada en la localidad de Cerro Colorado que involucra a proyectos en los Departamentos Río Seco, Sobremonte y Tulumba (Noroeste de la provincia de Córdoba, Argentina). El primer proyecto “Tulumba y sus sendas” trata de los diferentes circuitos turísticos en la Villa de Tulumba (Departamento Tulumba); el segundo, denominado “Vivencias camperas” propone vivenciar un día de campo en el establecimiento El Bordo situado en el Departamento Río Seco. El tercer proyecto plantea una “Raíz red turística” que comprende las localidades de Caminiaga, Cerro Colorado, Pozo Nuevo, San Francisco del Chañar y Villa María de Río Seco (Departamentos Río Seco y Sobremonte). “La huella de Don Ata”, en cuarto lugar, plantea un proyecto educativo relacionado al senderismo en la Comuna del Cerro Colorado. Finalmente, en “Soy el Mapa”, los autores proyectan el diseño de un cartel de interpretación ordenado en un solo punto que permita mostrar al turista los lugares relevantes del Cerro Colorado