Eimeria bovis is an important coccidian parasite that causes high economic losses in the cattle industry. We recently showed that polymorphonuclear neutrophils (PMN) react upon E. bovis sporozoite exposure by neutrophil extracellular trap (NET) formation. We focused here on the molecular mechanisms that are involved in this process. The sporozoite encounter led to an enhanced surface expression of neutrophil CD11b suggesting a potential role of this receptor in E. bovis-mediated NETosis. Antibody-mediated blockage of CD11b confirmed this assumption and led to a significantly decreased sporozoite-triggered NET. In addition, E. bovis-induced NETosis was found to be Ca2+-dependent since the inhibition of store-operated calcium entry (SOCE) significantly diminished NET. Furthermore, NADPH oxidase, neutrophil elastase (NE) and myeloperoxidase (MPO) were confirmed as key molecules in sporozoite-triggered NETosis, as inhibition thereof blocked parasite-triggered NET. PMN degranulation analyses revealed a significant release of matrix metalloprotease-9 containing granules upon sporozoite exposure. We further show a significantly enhanced phosphorylation of ERK1/2 and p38 MAPK in sporozoite-exposed PMN indicating a key role of this signaling pathway in E. bovis-mediated NETosis. Accordingly, ERK 1/2 and p38 MAPK inhibition led to a significant decrease in NET formation. Finally, we demonstrate that sporozoite-induced NETosis is neither a stage-, species-, nor host-specific process.

Long chain fatty acids (LCFAs), which are ligands for the G-protein coupled receptor FFAR1 (GPR40), are increased in cow plasma after parturition, a period in which they are highly susceptible to infectious diseases. This study identified and analyzed the functional role of the FFAR1 receptor in bovine neutrophils, the first line of host defense against infectious agents. We cloned the putative FFAR1 receptor from bovine neutrophils and analyzed the sequence to construct a homology model. Our results revealed that the sequence of bovine FFAR1 shares 84% identity with human FFAR1 and 31% with human FFAR3/GPR41. Therefore, we constructed a homology model of bovine FFAR1 using human as the template. Expression of the bovine FFAR1 receptor in Chinese hamster ovary (CHO)-K1 cells increased the levels of intracellular calcium induced by the LCFAs, oleic acid (OA) and linoleic acid (LA); no increase in calcium mobilization was observed in the presence of the short chain fatty acid propionic acid. Additionally, the synthetic agonist GW9508 increased intracellular calcium in CHO-K1/bFFAR1 cells. OA and LA increased intracellular calcium in bovine neutrophils. Furthermore, GW1100 (antagonist of FFAR1) and U73122 (phospholipase C (PLC) inhibitor) reduced FFAR1 ligand-induced intracellular calcium in CHO-K1/bFFAR1 cells and neutrophils. Additionally, inhibition of FFAR1, PLC and PKC reduced the FFAR1 ligand-induced release of matrix metalloproteinase (MMP)-9 granules and reactive oxygen species (ROS) production. Thus, we identified the bovine FFAR1 receptor and demonstrate a functional role for this receptor in neutrophils activated with oleic or linoleic acid.

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This study demonstrates that an activated-sludge wastewater treatment plant with UV disinfection reduces to levels below the detection limit those single-stranded RNA viruses as noroviruses and astroviruses and reach significant lower levels of rotaviruses and adenoviruses after the complete treatment process.

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MicroRNAs are related to human cancers, including cervical Background cancer (CC), which is mainly caused by human papillomavirus (HPV) infection. In 2012, approximately 70000 cases and 28000 deaths from this cancer were registered in Latin America according to GLOBOCAN reports. The most frequent genotype worldwide is HPV-16. The main molecular mechanism of HPV in CC is related to integration of viral DNA into the hosts' genome. However, the different variants in the human genome can result in different integration mechanisms, specifically involving microRNAs (miRNAs).: miRNA sequences associated with CC and four human genome Methods variants from Latin American populations were obtained from miRBase and the 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on human genomic variants. miRSNPs (single nucleotide polymorphisms in miRNAs) were identified in the miRNA sequences located at HPV integration sites on the human genomic Latin American variants.: Two hundred seventy-two miRNAs associated with CC were Results identified in 139 reports from different geographic locations. By mapping with the Blast-Like Alignment Tool (BLAT), 2028 binding sites were identified from these miRNAs on the human genome (version GRCh38/hg38); 42 miRNAs were located on unique integration sites; and miR-5095, miR-548c-5p and miR-548d-5p were involved with multiple genes related to the cell cycle. Thirty-seven miRNAs were mapped on the human Latin American genomic variants (PUR, MXL, CLM and PEL), but only miR-11-3p, miR-31-3p, miR-107, miR-133a-3p, miR-133a-5p, miR-133b, miR-215-5p, miR-491-3p, miR-548d-5p and miR-944 were conserved.: 10 miRNAs were conserved in the four human genome variants, Conclusions and in the remaining 27 miRNAs, substitutions, deletions or insertions were observed in the nucleotide sequences. This variability can imply differentiated mechanisms towards each genomic variant in human populations, relative to specific genomic patterns and geographic features. These findings may be decisive in determining susceptibility to the development of CC. Further identification of cellular genes and signalling pathways involved in CC progression could lead to the development of new therapeutic strategies based on miRNAs.

MicroRNAs are related to human cancers, including cervical Background cancer (CC) caused by HPV. In 2018, approximately 56.075 cases and 28.252 deaths from this cancer were registered in Latin America and the Caribbean according to GLOBOCAN reports. The main molecular mechanism of HPV in CC is related to integration of viral DNA into the hosts' genome. However, the different variants in the human genome can result in different integration mechanisms, specifically involving microRNAs (miRNAs).: The miRNAs associated with CC were obtained from literature, Methods the miRNA sequences and four human genome variants (HGV) from Latin American populations were obtained from miRBase and 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on HGV. miRSNPs were identified in the miRNA sequences located at HPV integration sites on the Latin American HGV.: Two hundred seventy-two miRNAs associated with CC were Results identified in 139 reports from different geographic locations. By mapping with Blast-Like Alignment Tool (BLAT), 2028 binding sites were identified from these miRNAs on the human genome (version GRCh38/hg38); 42 miRNAs were located on unique integration sites; and miR-5095, miR-548c-5p and miR-548d-5p were involved with multiple genes related to the cell cycle. Thirty-seven miRNAs were mapped on the Latin American HGV (PUR, MXL, CLM and PEL), but only miR-11-3p, miR-31-3p, miR-107, miR-133a-3p, miR-133a-5p, miR-133b, miR-215-5p, miR-491-3p, miR-548d-5p and miR-944 were conserved.: Ten miRNAs were conserved in the four HGV. In the Conclusions remaining 27 miRNAs, substitutions, deletions or insertions were observed. These variation patterns can imply differentiated mechanisms towards each genomic variant in human populations because of specific genomic patterns and geographic features. These findings may help in determining susceptibility for CC development. Further identification of cellular genes

Introducción: La información producida permanentemente por los registros poblacionales de cáncer es el insumo utilizado por los tomadores de decisiones del sistema de salud local y nacional para planificar las estrategias de prevención del cáncer y evaluar el impacto de sus intervenciones. Objetivo: Determinar la incidencia y mortalidad por cáncer en el municipio de Pasto Colombia periodo 2013-2017. Métodos: Estudio observacional descriptivo de la morbimortalidad por cáncer. La recolección y procesamiento de información se realizaron siguiendo recomendaciones del IARC. Las tasas se calcularon según sexo, edad y ubicación del tumor. Resultados: La incidencia global de cáncer fue de 3.759 casos, 1.608 en hombres (Tasa Estandarizada de Edad TAE= 169.4 casos/100,000 hombres-año) y 2.151 casos en mujeres (TAE= 176.6 casos/100,000 mujeres-año). Los tumores más frecuentes en hombres fueron: próstata (25.9%), estómago (16.5%) y pulmón (4.8%) y en mujeres:mama (19.7%), tiroides (12.2%) y cérvix (10.6%). Se presentaron 2.130 muertes por cáncer, 934 en hombres (TAE=97.8 muertes/100,000 hombres-año) y 1.196 muertes en mujeres (TAE=95.1 muertes/100,000 mujeres-año). Las principales causas de mortalidad en hombres fueron los tumores de estómago (24.8%), próstata (12.8%) y pulmón (7.5%). En mujeres: mama (12.2%), estómago (11.6%) y cérvix (10.0%). Conclusiones: El seguimiento quinquenal de los indicadores de carga de cáncer permite realizar comparaciones a nivel nacional e internacional con el fin de ofrecer las bases para planificar y evaluar la implementación de las políticas públicas de salud, relacionadas con la prevención y atención de las causas más comunes de morbimortalidad en Pasto-Colombia.