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hnological requirement, and may be completed within a single working day. Resulting MLVA profiles can be readily shared and compared across laboratories, facilitating rapid placement of samples in an international ezpizootiological context.Adult T cell leukemia-lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-I) retrovirus. ATL carries a dismal prognosis. ATL classifies into four subtypes (acute, lymphoma, chronic, and smoldering) which display different clinical features, prognosis and response to therapy, hence requiring different clinical management. Smoldering and chronic subtypes respond well to antiretroviral therapy using the combination of zidovudine (AZT) and interferon-alpha (IFN) with a significant prolongation of survival. Conversely, the watch and wait strategy or chemotherapy for these indolent subtypes allies with a poor long-term outcome. Acute ATL is associated with chemo-resistance and dismal prognosis. Lymphoma subtypes respond better to intensive chemotherapy but survival remains poor. Allogeneic hematopoietic stem cell transplantation (HSCT) results in long-term survival in roughly one third of transplanted patients but only a small percentage of patients can make it to transplant. Overall, current treatments of aggressive ATL are not satisfactory. Prognosis of refractory or relapsed patients is dismal with some encouraging results when using lenalidomide or mogamulizumab. To overcome resistance and prevent relapse, preclinical or pilot clinical studies using targeted therapies such as arsenic/IFN, monoclonal antibodies, epigenetic therapies are promising but warrant further clinical investigation. Anti-ATL vaccines including Tax peptide-pulsed dendritic cells, induced Tax-specific CTL responses in ATL patients. Finally, based on the progress in understanding the pathophysiology of ATL, and the risk-adapted treatment approaches to different ATL subtypes, treatment strategies of ATL should take into account the host immune responses and the host microenvironment including HTLV-1 infected non-malignant cells. Herein, we will provide a summary of novel treatments of ATL in vitro, in vivo, and in early clinical trials.Leishmania infantum is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient. It is important to know Leishmania virulence factors that contribute most to the disease in order to develop drugs. In the present work, we have produced L. infantum prolyl oligopeptidase (rPOPLi) in Escherichia coli, and investigated its biochemical properties as well as the effect of POP inhibitors on its enzymatic activity and on the inhibition of the macrophage infection by L. infantum. The optimal activity occurred at pH 7.5 and 37°C in the presence of DTT, the latter increased rPOPLi catalytic efficiency 5-fold on the substrate N-Suc-Gly-Pro-Leu-Gly-Pro-AMC. The enzyme was inhibited by TPCK, TLCK and by two POP specific inhibitors, Z-Pro-prolinal (ZPP, IC50 4.2 nM) and S17092 (IC50 3.5 nM). Besides being a cytoplasmic enzyme, POPLi is also found in punctuate structures within the parasite cytoplasm or associated with the parasite plasma membrane in amastigotes and promastigotes, respectively. Interestingly, S17092 and ZPP prevented parasite invasion in murine macrophages, supporting the involvement of POPLi in the invasive process of L. infantum. These data suggest POPLi as a virulence factor that offers potential as a target for designing new antileishmanial drugs.The study of the gut microbiome in threatened wildlife species has enormous potential to improve conservation efforts and gain insights into host-microbe coevolution. Threatened species are often housed in captivity, and during this process undergo considerable changes to their gut microbiome. Studying the gut microbiome of captive animals therefore allows identification of dysbiosis and opportunities for improving management practices in captivity and for subsequent translocations. Manipulation of the gut microbiome through methods such as fecal transplant may offer an innovative means of restoring dysbiotic microbiomes in threatened species to provide health benefits. Finally, characterization of the gut microbiome (including the viral components, or virome) provides important baseline health information and may lead to discovery of significant microbial pathogens. Here we summarize our current understanding of microbiomes in Australian marsupial species.Snow packs cover large expanses of Earth's land surface, making them integral components of the cryosphere in terms of past climate and atmospheric proxies, surface albedo regulators, insulators for other Arctic environments and habitats for diverse microbial communities such as algae, bacteria and fungi. Yet, most of our current understanding of snow pack environments, specifically microbial activity and community interaction, is limited to the main microbial growing season during spring ablation. At present, little is known about microbial activity and its influence on nutrient cycling during the subfreezing temperatures and 24-h darkness of the polar winter. Here, we examined microbial dynamics in a simulated cold (-5°C), dark snow pack to determine polar winter season microbial activity and its dependence on critical nutrients. Snow collected from Ny-Ålesund, Svalbard was incubated in the dark over a 5-week period with four different nutrient additions, including glacial mineral particles, dissolved inorge ice and downstream environments during the ablation season.The toxic cyanobacterium Microcystis is one of the most pervasive harmful algal bloom (HAB) genera and naturally occurs in large colonies known to harbor diverse heterotrophic bacterial assemblages. While colony-associated microbiomes may influence Microcystis blooms, there remains a limited understanding of the structure and functional potential of these communities and how they may be shaped by changing environmental conditions. To address this gap, we compared the dynamics of Microcystis-attached (MCA), free-living (FL), and whole water (W) microbiomes during Microcystis blooms using next-generation amplicon sequencing (16S rRNA), a predictive metagenome software, and other bioinformatic approaches. Microbiomes were monitored through high resolution spatial-temporal surveys across two North American lakes, Lake Erie (LE) and Lake Agawam (LA; Long Island, NY, United States) in 2017, providing the largest dataset of these fractions to date. Sequencing of 126 samples generated 7,922,628 sequences that clusterMicrocystis blooms during low N conditions. The MCA predicted metagenomes were conserved over 8 months of seasonal changes in temperature and N availability despite strong temporal succession in microbiome composition. Collectively, these findings indicate that Microcystis colonies harbor a statistically distinct microbiome with a conserved functional potential that may help facilitate bloom persistence under environmentally unfavorable conditions.The changes of gastric microbiome across stages of neoplastic progression remain poorly understood, especially for intraepithelial neoplasia (IN) which has been recognized as a phenotypic bridge between atrophic/intestinal metaplastic lesions and invasive cancer. The gastric microbiota was investigated in 30 healthy controls (HC), 21 non-atrophic chronic gastritis (CG), 27 gastric intestinal metaplasia (IM), 25 IN, and 29 gastric cancer (GC) patients by 16S rRNA gene profiling. The bacterial diversity, and abundances of phyla Armatimonadetes, Chloroflexi, Elusimicrobia, Nitrospirae, Planctomycetes, Verrucomicrobia, and WS3 reduced progressively from CG, through IM, IN to GC. Actinobacteria, Bacteriodes, Firmicutes, Fusobacteria, SR1, and TM7 were enriched in the IN and GC. At the community level, the proportions of Gram-positive and anaerobic bacteria increased in the IN and GC compared to other histological types, whereas the aerobic and facultatively anaerobic bacteria taxa were significantly reduced in GC. Remarkable changes in the gastric microbiota functions were detected after the formation of IN. The reduced nitrite-oxidizing phylum Nitrospirae together with a decreased nitrate/nitrite reductase functions indicated nitrate accumulation during neoplastic progression. We constructed a random forest model, which had a very high accuracy (AUC > 0.95) in predicating the histological types with as low as five gastric bacterial taxa. In summary, the changing patterns of the gastric microbiota composition and function are highly indicative of stages of neoplastic progression.Colaphellus bowringi Baly mainly damages cruciferous vegetables, leading to huge economic losses. The secretory insecticidal protein (Sip) of Bacillus thuringiensis (Bt) has high insecticidal activity against C. bowringi Baly. The tertiary structure of Sip1Aa protein was analyzed by homologous modeling and other bioinformatics methods to predict the conserved domain of Sip1Aa protein. Acidic and basic amino acids in the conserved domain were selected, and alanine was used to replace these amino acids by site-directed mutation. The difference between the insecticidal activities of mutant protein and Sip1Aa protein was analyzed. The insecticidal activities of H99A, K109A, K128A, and E130A against C. bowringi Baly were significantly increased, among which that of K128A was the most obviously changed, and the LC50 value was decreased by about 10 times compared with that of Sip1Aa protein. The LC50 value of mutant E130A was 0.286 μg/mL, which was about six times less than that of Sip1Aa. K128 and E130 were both in the β9-β10 loop. The toxicity of D290A, H242A, and H303A to C. bowringi Baly was significantly reduced, and their LC50 value increased by about six, eight, and three times compared with that of Sip1Aa protein, respectively. This study showed that acidic and basic amino acid residues played a certain role in the toxicity of Sip1Aa protein, and the loss of side chains in key residues had a significant impact on the insecticidal activity of the protein. This study provides the theoretical basis for revealing the relationship between the structure and function of Sip1Aa protein and also provides a new method for the subsequent study of sip gene.Mitochondrial genomes (mt-genomes) are characterized by a distinct codon usage and their autonomous replication. Mt-genomes encode highly conserved genes (mt-genes), like proteins involved in electron transport and oxidative phosphorylation but they also carry highly variable regions that are in part responsible for their high plasticity. The degree of conservation of their genes is such that they allow the establishment of phylogenetic relationships even across distantly related species. Here, we describe the mechanisms that generate changes along mt-genomes, which play key roles at enlarging the ability of fungi to adapt to changing environments. Within mt-genomes of fungal pathogens, there are dispensable as well as indispensable genes for survival, virulence and/or pathogenicity. We also describe the different complexes or mechanisms targeted by fungicides, thus addressing a relevant issue regarding disease management. Despite the controversial origin and evolution of fungal mt-genomes, the intrinsic mechanisms and molecular biology involved in their evolution will help to understand, at the molecular level, the strategies for fungal disease management.
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