Virulence potential and genetic diversity of Aeromonas caviae, Aeromonas veronii, and Aeromonas hydrophila clinical isolates from Mexico and Spain: a comparative study

A comparative study of 109 Aeromonas clinical isolates belonging to the 3 species most frequently isolated from patients with diarrhea in Mexico and Spain was performed to investigate the distribution of 3 prominent toxin genes and the gene encoding flagellin of lateral flagella; 4 well-established virulence factors in the genus Aeromonas. The aerolysin-hemolysin toxin genes were the most prevalent, being present in 89% of the total isolates. The ast toxin gene was conspicuously absent from the Aeromonas caviae and Aeromonas veronii groups but was present in 91% of the Aeromonas hydrophila isolates. Both the alt toxin gene and the lafA flagellin gene also had a low incidence in A. caviae and A. veronii. Differences in the prevalence of alt and lafA were observed between isolates from Mexico and Spain, confirming genus heterogeneity according to geographic location. Carriage of multiple toxin genes was primarily restricted to A. hydrophila isolates, suggesting that A. caviae and A. veronii isolates circulating in Mexico and Spain possess a limited array of virulence genes. Enterobacterial repetitive intergenetic consensus - polymerase chain reaction showed that the Aeromonas populations sampled lack dominant clones and were genetically heterogeneous, with A. caviae being the most diverse species. Further surveys of virulence determinants in genetically heterogeneous populations of Aeromonas isolates circulating worldwide are required to enhance the understanding of their capacity to cause disease.     

P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration

Polarized cell migration results from the transduction of extra-cellular cues promoting the activation of Rho GTPases with the intervention of multidomain proteins, including guanine exchange factors. P-Rex1 and P-Rex2 are Rac GEFs connecting Gbetagamma and phosphatidylinositol 3-kinase signaling to Rac activation. Their complex architecture suggests their regulation by protein-protein interactions. Novel mechanisms of activation of Rho GTPases are associated with mammalian target of rapamycin (mTOR), a serine/threonine kinase known as a central regulator of cell growth and proliferation. Recently, two independent multiprotein complexes containing mTOR have been described. mTORC1 links to the classical rapamycin-sensitive pathways relevant for protein synthesis; mTORC2 links to the activation of Rho GTPases and cytoskeletal events via undefined mechanisms. Here we demonstrate that P-Rex1 and P-Rex2 establish, through their tandem DEP domains, interactions with mTOR, suggesting their potential as effectors in the signaling of mTOR to Rac activation and cell migration. This possibility was consistent with the effect of dominant-negative constructs and short hairpin RNA-mediated knockdown of P-Rex1, which decreased mTOR-dependent leucine-induced activation of Rac and cell migration. Rapamycin, a widely used inhibitor of mTOR signaling, did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex. mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration.     

A1298C polymorphism of the MTHFR gene and neural tube defects in the state of Yucatan, Mexico

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) of the folate metabolism pathway is a candidate gene for neural tube defects (NTDs). Frequency of the second common polymorphism, A1298C, in the MTHFR gene is not well known in Mexico. Conflicting results exist regarding the association of A1298C-MTHFR with NTDs. One explanation for this controversy might be that alleles are differently distributed among various populations. The aim of the study was to determine the frequency of the A1298C-MTHFR polymorphism and its association with NTDs in a population of Yucatan, Mexico. METHODS: Genotyping was performed by use of polymerase chain reaction with restriction fragment length polymorphisms using MbOII endonuclease (PCR-RFLPs MbOII). Allele and genotype frequencies were compared between cases with NTDs, their mothers and fathers with matched controls based on an association analysis using EpiInfo software. RESULTS: A1298C genotypes were distributed according to Hardy-Weinberg expectations for all studied groups. Frequencies of allele C and heterozygous AC genotype were significantly higher in males (p = .006 and p = .011, respectively) in control group. Significant differences were not observed between cases and controls, except in mothers of NTD cases compared with mothers of healthy offspring for both allele C and heterozygous AC genotype (p = .009 and p = .01, respectively). CONCLUSIONS: The polymorphism A1298C-MTHFR is not associated with NTDs, except for mothers, suggesting only a maternal association with having NTD-affected offspring in the Yucatan population. The frequency of allele C in the control population was 10%, which is significantly lower than in other reported control populations worldwide (p < .01).     

Reclassification of aortic stenosis by fusion of echocardiography and computed tomography in low-gradient aortic stenosis

Netherlands Heart Journal - The integration of computed tomography (CT)-derived left ventricular outflow tract area into the echocardiography-derived continuity equation results in the...     

Molecular Insights on the Release of Avibactam from the Acyl-Enzyme Complex

Avibactam is a non-β-lactam β-lactamase inhibitor for treating complicated urinary tract and respiratory infections caused by multidrug-resistant bacterial pathogens, a serious public health threat. Despite its importance, the release mechanism of avibactam from the enzyme-inhibitor complex has been scarcely studied from first principles, considering the total protein environment. This information at the molecular level is essential for the rational design of new antibiotics and inhibitors. In this article, we addressed the release of avibactam from the complex CTX-M-15 by means of molecular dynamics simulations and quantum mechanics/molecular mechanics calculations. This study provides molecular information not available earlier, including exploration of the potential energy surfaces, characterization of the observed intermediate, and their critical points, as well. Our results show that unlike that observed in the acylation reaction, the residues Glu166 and Lys73 would be in their neutral forms. Release of avibactam follows a stepwise mechanism in which the first stage corresponds to the formation of a tetrahedral intermediate, whereas the second stage corresponds to the cleavage of the Ser70-C7 bond, mediated by Lys73, either directly or through Ser130.     

Spontaneous meningoencephalitis by Staphylococcus aureus in an infant golden‐headed lion tamarin (Leontopithecus chrysomelas)

Non‐human primates are susceptible to many bacteria, some of which bear zoonotic potential. We report the pathologic features of spontaneous fulminating meningoencephalitis by Staphylococcus aureus in a captive infant golden‐headed lion tamarin (Leontopithecus chrysomelas) from Brazil.     

Vertical distribution of epiphytic lichens on Quercus laurina Humb. & Bonpl. in a remnant of cloud forest in the state of Veracruz,México

In the tropics, corticolous lichen richness and cover tend to increase from the trunk base to the top of the crown of trees. In this study we calculated the total beta diversity of the lichen community along a vertical gradient on Quercus laurina in Mexican cloud forest. By comparing the richness and cover of the lichens by zone, we show that foliose and fruticose lichens are a minor component of the total lichen species richness, but have a higher cover than the crustose lichens. Five zones were identified along each phorophyte (n = 15) with a diameter at breast height >40 cm. A total of 92 species were identified. Of these, 38% were found only in a single zone, 51% were shared between the different zones and 11% occurred across all zones. Species richness and cover increased from the lowest to the highest zones of the phorophytes. Dissimilarity in species composition between the zones could be explained by species replacement. An indicator species analysis revealed that only a few species, e.g. Hypotrachyna vexans, H. cf. sublaevigata and Ramalina cf. sinaloensis prefer a particular zone. The results show that the lichen community associated with Quercus laurina phorophytes is highly diverse and suggest that species richness and cover are related to the zone and the various growth forms.     

The Administration of Cadmium for 2, 3 and 4 Months Causes a Loss of Recognition Memory,Promotes Neuronal Hypotrophy and Apoptosis in the Hippocampus of Rats

Cadmium (Cd) is a toxic metal and classified as a carcinogen whose exposure could affect the function of the central nervous system. There are studies that suggest that Cd promotes neurodegeneration in different regions of the brain, particularly in the hippocampus. It is proposed that its mechanism of toxicity maybe by an oxidative stress pathway, which modifies neuronal morphology and causes the death of neurons and consequently affecting cognitive tasks. However, this mechanism is not yet clear. The aim of the present work was to study the effect of Cd administration on recognition memory for 2, 3 and 4 months, neuronal morphology and immunoreactivity for caspase-3 and 9 in rat hippocampi. The results show that the administration of Cd decreased recognition memory. Likewise, it caused the dendritic morphology of the CA1, CA3 and dentate gyrus regions of the hippocampus to decrease with respect to the time of administration of this heavy metal. In addition, we observed a reduction in the density of dendritic spines as well as an increase in the immunoreactivity of caspase-3 and 9 in the same hippocampal regions of the animals treated with Cd. These results suggest that Cd affects the structure and function of the neurons of the hippocampus, which contribute to the deterioration of recognition memory. Our results suggest that the exposure to Cd represents a critical health problem, which if not addressed quickly, could cause much more serious problems in the quality of life of the human population, as well as in the environment in which they develop.

     

Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway

Calcium sensing receptor, a pleiotropic G protein coupled receptor, activates secretory pathways in cancer cells and putatively exacerbates their metastatic behavior. Here, we show that various CaSR mutants, identified in breast cancer patients, differ in their ability to stimulate Rac, a small Rho GTPase linked to cytoskeletal reorganization and cell protrusion, but are similarly active on the mitogenic ERK pathway. To investigate how CaSR activates Rac and drives cell migration, we used invasive MDA-MB-231 breast cancer cells. We revealed, by pharmacological and knockdown strategies, that CaSR activates Rac and cell migration via the Gβγ-PI3K-mTORC2 pathway. These findings further support current efforts to validate CaSR as a relevant therapeutic target in metastatic cancer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00662-y.