40 research outputs found

    Genome Sequence and Comparative Genome Analysis of Lactobacillus casei: Insights into Their Niche-Associated Evolution

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    Lactobacillus casei is remarkably adaptable to diverse habitats and widely used in the food industry. To reveal the genomic features that contribute to its broad ecological adaptability and examine the evolution of the species, the genome sequence of L. casei ATCC 334 is analyzed and compared with other sequenced lactobacilli. This analysis reveals that ATCC 334 contains a high number of coding sequences involved in carbohydrate utilization and transcriptional regulation, reflecting its requirement for dealing with diverse environmental conditions. A comparison of the genome sequences of ATCC 334 to L. casei BL23 reveals 12 and 19 genomic islands, respectively. For a broader assessment of the genetic variability within L. casei, gene content of 21 L. casei strains isolated from various habitats (cheeses, n = 7; plant materials, n = 8; and human sources, n = 6) was examined by comparative genome hybridization with an ATCC 334-based microarray. This analysis resulted in identification of 25 hypervariable regions. One of these regions contains an overrepresentation of genes involved in carbohydrate utilization and transcriptional regulation and was thus proposed as a lifestyle adaptation island. Differences in L. casei genome inventory reveal both gene gain and gene decay. Gene gain, via acquisition of genomic islands, likely confers a fitness benefit in specific habitats. Gene decay, that is, loss of unnecessary ancestral traits, is observed in the cheese isolates and likely results in enhanced fitness in the dairy niche. This study gives the first picture of the stable versus variable regions in L. casei and provides valuable insights into evolution, lifestyle adaptation, and metabolic diversity of L. casei

    MicroRNA degradation by a conserved target RNA regulates animal behavior

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    International audiencemicroRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3′ UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3′ trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavio

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Hydrogen sulfide causes excision of a genomic island in Pseudomonas syringae pv. phaseolicola

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    © 2017, The Author(s). Hydrogen sulfide (H2S) is known to be an important signalling molecule in both animals and plants, despite its toxic nature. In plants it has been seen to control stomatal apertures, so altering the ability of bacteria to invade plant tissues. Bacteria are known to generate H2S as well as being exposed to plant-generated H2S. During their interaction with plants pathogenic bacteria are known to undergo alterations to their genomic complement. For example Pseudomonas syringae pv. phaseolicola (Pph) strain 1302A undergoes loss of a section of DNA known as a genomic island (PPHGI-1) when exposed to the plants resistance response. Loss of PPHGI-1 from Pph 1302A enables the pathogen to overcome the plants resistance response and cause disease. Here, with the use of H2S donor molecules, changes induced in Pph 1302A genome, as demonstrated by excision of PPHGI-1, were investigated. Pph 1302A cells were found to be resistant to low concentrations of H2S. However, at sub-lethal H2S concentrations an increase in the expression of the PPHGI-1 encoded integrase gene (xerC), which is responsible for island excision, and a subsequent increase in the presence of the circular form of PPHGI-1 were detected. This suggests that H2S is able to initiate excision of PPHGI-1 from the Pph genome. Therefore, H2S that may emanate from the plant has an effect on the genome structure of invading bacteria and their ability to cause disease in plants. Modulation of such plant signals may be a way to increase plant defence responses for crops in the future

    Antitumor activity of new chemical compounds in triple negative mammary adenocarcinoma models

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    Aim: According to the need for the development of new anticancer agents, we have synthetized novel bioactive compounds and aimed to determine their antitumor action. Materials & methods: We describe in vitro studies evaluating the effect of 35 novel chemical compounds on two triple negative murine mammary adenocarcinoma tumors. Results & conclusion: Three compounds were selected because of their high antitumor activity and their low toxicity to normal cells. Their effect on tumor cells apoptosis, clonogenicity and migratory capacity, were determined. We found that the selected compounds showed inhibition of viability and clonogenic capacity, and promotion of apoptosis. They also decreased the migratory capacity of tumor cells. The results obtained suggest the likelihood of their future use as antitumor and/or antimetastatic agents.In spite of the important progress achieved in cancer therapeutics, the percentage of people dying because of cancer is still high. Hence, we need to develop new, effective and nontoxic anticancer agents. We synthetized novel compounds and tested their antitumor effect and toxicity, in order to choose those that are effective and do not affect normal cells and therefore, are suitable for human cancer therapies. We selected three out of 35 compounds that show high antitumor action and low toxicity. Also, we studied the mechanisms by which that effect was achieved. Our next goal is to develop experiments with animals in order to have preclinical data that, hopefully, will lead to the clinical use of one or more of the selected compounds.Fil: Giolito, Maria Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentin

    Supplementary Materials - Antitumor activity of new chemical compounds in triple negative mammary adenocarcinoma models

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    Aims. According to the need for the development of new anticancer agents, we have synthetized novel bioactive compounds and aimed to determine their antitumor action. Materials & Methods. We describe in vitro studies evaluating the effect of 35 novel chemical compounds on two triple negative murine mammary adenocarcinoma tumors. Results & Conclusions. Three compounds were selected because of their high antitumor activity and their low toxicity to normal cells. Their effect on tumor cells apoptosis, clonogenicity and migratory capacity, were determined. We found that the selected compounds showed inhibition of viability and clonogenic capacity, and promotion of apoptosis. They also decreased the migratory capacity of tumor cells. The results obtained suggest the likelihood of their future use as antitumor and/or antimetastatic agents SM1: Methodology and characterization of the chemical compounds SM2: Chemical structure of the compounds belonging to each family SM3: Effect of the compounds (100 µM) on 4T1 cells viability. Cells were incubated for 36 hs in complete medium with 100 µM of each compound. Viable cell number was evaluated with WST-1. Results are shown as percentage of cell viability relative to the non-treated control (100%) and expressed as mean ± SEM. Experiments were performed in triplicate. SM4: Effect of the compounds (75 µM) on 4T1 cells viability. Cells were incubated for 36 hs in complete medium with 75 µM of each compound. Viable cell number was evaluated with WST-1. Results are shown as percentage of cell viability relative to the non-treated control (100%) and expressed as mean ± SEM. Experiments were performed in triplicate. SM5: Effect of the compounds (50 and 25 µM) on 4T1 cells viability. A) Cells were incubated for 36 hs in complete medium with 50 µM of each compound; B) Cells were incubated for 36 hs in complete medium with 25 µM of each compound. Viable cell number was evaluated with WST-1. Results are shown as percentage of cell viability relative to the non-treated control (100%) and expressed as mean ± SEM. Experiments were performed in triplicate. SM6: The percent of viability of the selected compounds at 25 µ
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