Can miRNA Indicate Risk of Illness after Continuous Exposure to M. tuberculosis?

Simple SummaryTuberculosis is the leading cause of mortality from a single infectious agent and is among the top 10 causes of death worldwide. Despite that, few studies focus on regulatory elements such as small non-coding RNAs in tuberculosis. This pilot work applied Next Generation Sequencing techniques to evaluate the global miRNA expression profile of patients with active tuberculosis; their respective healthy physicians, who are at constant risk of infection; and a second group of healthy controls. In addition, we observed miRNA–gene interactions affected by exposure to the bacteria. Our findings indicate a list of miRNAs that could be used as potential biomarkers to improve treatment strategies at early stages. We also observed modified pathways related to the immune response due to differential miRNA expression profiles. Finally, we alert and encourage the development of new strategies to avoid long-term exposure of healthy physicians, considering how closely related their miRNA profile was to tuberculosis patients using current safety protocols.AbstractThe role of regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humans and it is still a challenge to prevent and treat. Control of the infection, as well as its diagnosis, are still complex and current treatments used are linked to several side effects. This study aimed to identify possible biomarkers for tuberculosis by applying NGS techniques to obtain global miRNA expression profiles from 22 blood samples of infected patients with tuberculosis (n = 9), their respective healthy physicians (n = 6) and external healthy individuals as controls (n = 7). Samples were run through a pipeline consisting of differential expression, target genes, gene set enrichment and miRNA–gene network analyses. We observed 153 altered miRNAs, among which only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results indicate that miRNAs may be involved in immune modulation by regulating gene expression in cells of the immune system. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.     

Evaluation of the N2O emissions from N in plant residues as affected by environmental and management factors

A review of the N₂O-N emission from crop residues was conducted based on new data published during the last decade. The result indicated that factors as type of crop, biochemical quality of residues, agricultural management, climate and season of the year, soil properties and soil moisture play a significant role in the rate of N₂O-N emissions. An emission factor (EF) equal to 1.055% of N applied in plant residues – derived from a simple linear regression of emitted N₂O-N (kg ha^?1) on N applied in crop residues (kg ha^?1) – represent an estimate that explains about 60% of emission variations. However, the EF of N applied in plant residues is not a constant but a variable coefficient that depends on environmental and management variables. The following two linear models – that estimate emitted N₂O-N (kg ha^?1) as a function of the variables N (kg ha^?1) applied in plant residues (NPR), rain (mm), temperature (°C) and temperature²(°C²) – were fitted to the dataset with 45 observations obtained from the reviewed literature. $$\hskip1.5pc\hbox{N}_{2}\hbox{O}\hbox{-}\hbox{N}=-4.154+0.00955\hbox{ NPR}+1.7278\hbox{ ApM}+0.003996\hbox{ Rain }+0.6242\hbox{ Tem }-0.0230\hbox{ Tem}^{2}$$ and $$\hbox{N}_{2}\hbox{O}\hbox{-}\hbox{N}= 0.6535 + [-0.0404 + 0.0078\hbox{ ApM }+ 0.000044\hbox{ Rain }+ 0.00567\hbox{ Tem }-0.0001975\hbox{ Tem}^{2}]\hbox{ NPR }$$ Both models provided almost equally good statistical fit to the data, with R ²=0.832 and R ²=0.829, respectively, and most regression coefficients being significant at $P < 0.01$ . Because of its internal structure, the second model is more appealing as it represents N₂O-N emission as a transformation that is affected by management and environmental variables. The following expression – that correspond to the quantities in the square bracket at the right hand side of the second model – is the coefficient for the variable N applied in crop residues, and represent the emission factor as a function of application method of plant residues, rain, temperature and temperature². $$\hskip3.5pc\hbox{EF }=-0.0404+0.0078\hbox{ ApM }+0.000044\hbox{Rain }+0.00567\hbox{ Tem }- 0.0001975\hbox{ Tem}^{2}$$ Standardization of research methodologies and data gathering and reporting, including kind of crop, N content of applied residues, agricultural management, length of the measuring period, climate, soils properties, soil temperature and water content, would facilitate further advances in studies oriented to increase the precision of N₂O-N emission estimates.     

Synthesis, characterization and biological activity of trans-platinum(II) and trans-platinum(IV) complexes with 4-hydroxymethylpyridine

The synthesis and chemical characterization of two new trans platinum complexes, trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] (1) and trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] (2) are described. Their ability to interact with 5'-GMP by themselves and in the presence of reducing agents in the case of trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] were tested. Circular dichroism, electrophoretic mobility in agarose gel, and atomic force microscopy studies showed that the interaction of complex 1 with DNA is stronger than that of complex 2. Cytotoxicity tests against HL-60 tumor cells also showed higher activity for trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] than for trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)]. Complex 1 presents similar behavior to cisplatin, but with a lower IC(50) at 24 h. Complex 1 also showed high apoptosis induction.