MDA5 RNA-sensing pathway activation by Mycobacterium tuberculosis promotes innate immune subversion and pathogen survival.

Host cytosolic sensing of Mycobacterium tuberculosis (M. tuberculosis) RNA by the RIG-I-like receptor (RLR) family perturbs innate immune control within macrophages; however, a distinct role of MDA5, a member of the RLR family, in M. tuberculosis pathogenesis has yet to be fully elucidated. To further define the role of MDA5 in M. tuberculosis pathogenesis, we evaluated M. tuberculosis intracellular growth and innate immune responses in WT and Mda5-/- macrophages. Transfection of M. tuberculosis RNA strongly induced proinflammatory cytokine production in WT macrophages, which was abrogated in Mda5-/- macrophages. M. tuberculosis infection in macrophages induced MDA5 protein expression, accompanied by an increase in MDA5 activation as assessed by multimer formation. IFN-γ-primed Mda5-/- macrophages effectively contained intracellular M. tuberculosis proliferation to a markedly greater degree than WT macrophages. Further comparisons of WT versus Mda5-/- macrophages revealed that during M. tuberculosis infection MDA5 contributed to IL-1ß production and inflammasome activation and that loss of MDA5 led to a substantial increase in autophagy. In the mouse TB model, loss of MDA5 conferred host survival benefits with a concomitant reduction in M. tuberculosis bacillary burden. These data reveal that loss of MDA5 is host protective during M. tuberculosis infection in vitro and in vivo, suggesting that M. tuberculosis exploits MDA5 to subvert immune containment.

Colistin-induced Bartter-like Syndrome: Ponder before Treatment!

Bartter-like syndrome (BLS) is a constellation of biochemical abnormalities which include metabolic alkalosis, hypokalemia, hypocalcemia, hypomagnesemia with normal kidney function. BLS is a very rare syndrome and can be induced by certain diseases, antibiotics, diuretics, and antineoplastic drugs. Colistin is a polymicrobial bactericidal drug and currently re-emerged as the only salvation therapy against multidrug resistant bacilli especially in critically ill patients at intensive care units. Only an anecdotal case report of colistin-induced Bartter-like syndrome has been reported. We here report a case series of four critically ill patients who were on treatment with colistin and presented with serious metabolic disturbances. How to cite this article: Kumari A, Gupta P, Verma H, Kumar A, Thakur P, Sharma K. Colistin-induced Bartter-like Syndrome: Ponder before Treatment! Indian J Crit Care Med 2022;26(2):239-243.

Nanoferrites heterogeneous catalysts for biodiesel production from soybean and canola oil: a review.

Fossil fuel depletion and pollution are calling for alternative, renewable energies such as biofuels. Actual challenges include the design of efficient processes and catalysts to convert various feedstocks into biofuels. Here, we review nanoferrites heterogeneous catalysts to produce biodiesel from soybean and canola oil. For that, transesterification is the main synthesis route and offers simplicity, cost-effectiveness, better process control, and high conversion yield. Catalysis with nanoferrites and composites allow to obtain yields higher than 95% conversion with less than 5.0 wt.% of catalyst loading at 80 °C in 1-2 h. More than 90% conversion yields can be achieved with a moderate alcohol/oil molar ratio, i.e., between 12:1 to 16:1. Catalyst recovery is easy due to the magnetic properties of nanoferrite, which can be effectively reused up to 4 times with less than 10% loss of catalytic efficiency.

Relative and Quantitative Phosphoproteome Analysis of Macrophages in Response to Infection by Virulent and Avirulent Mycobacteria Reveals a Distinct Role of the Cytosolic RNA Sensor RIG-I in Mycobacterium tuberculosis Pathogenesis.

Comparative phosphoproteomics of Mycobacterium tuberculosis (Mtb)- and Mycobacterium bovis BCG (BCG)-infected macrophages could be instrumental in understanding the characteristic post-translational modifications of host proteins and their subsequent involvement in determining Mtb pathogenesis. To identify proteins acquiring a distinct phosphorylation status, herein, we compared the phosphorylation profile of macrophages upon exposure to Mtb and BCG. We observed a significant dephosphorylation of proteins following Mtb infection relative to those with uninfected or BCG-infected cells. A comprehensive tandem mass tag mass spectrometry (MS) approach detected ∼10% phosphosites on a variety of host proteins that are modulated in response to infection. Interestingly, the innate immune-enhancing interferon (IFN)-stimulated genes were identified as a class of proteins differentially phosphorylated during infection, including the cytosolic RNA sensor RIG-I, which has been implicated in the immune response to bacterial infection. We show that Mtb infection results in the activation of RIG-I in primary human macrophages. Studies using RIG-I knockout macrophages reveal that the Mtb-mediated activation of RIG-I promotes IFN-ß, IL-1α, and IL-1ß levels, dampens autophagy, and facilitates intracellular Mtb survival. To our knowledge, this is the first study providing exhaustive information on relative and quantitative changes in the global phosphoproteome profile of host macrophages that can be further explored in designing novel anti-TB drug targets. The peptide identification and MS/MS spectra have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD013171.

A review on MnZn ferrites: Synthesis, characterization and applications.

Researchers are taking great interest in the synthesis and characterization of MnZn ferrites due to their wide range of applications in many areas. MnZn ferrites are a class of soft magnetic materials that have very good electrical, magnetic and optical properties. The properties of MnZn ferrites include high value of resistivity, permeability, permittivity, saturation magnetization, low power losses and coercivity. The above mentioned advantageous features of MnZn ferrites make them suitable for the use in various applications. In biomedical field these ferrites are used for cancer treatment and MRI. MnZn ferrites are also used in electronic applications for making transformers, transducers and inductors. These ferrites are also used in magnetic fluids, sensors and biosensors. MnZn ferrite is highly useful material for several electrical and electronic applications. It finds applications in almost every household appliances like mobile charger, LED bulb, TV, refrigerator, juicer mixer, washing machine, iron, microwave oven, mobile, laptop, desktop, printer and so on. Therefore, the present review focuses on different techniques for synthesis of MnZn ferrites in literature, their characterization tools, effect of doping on the properties of MnZn ferrite and finally we will discuss about their applications.

Nanomaterial Fungicides: In Vitro and In Vivo Antimycotic Activity of Cobalt and Nickel Nanoferrites on Phytopathogenic Fungi.

Recent advances in engineering lead to the fabrication of nanomaterials with unique properties targeted toward specific applications. The use of nanotechnology in agriculture, in particular for plant protection and production, is an under-explored area in the research community. Fungal diseases are one of the leading causes of crop destruction and, in this context, the antifungal effect of nanoparticles of cobalt and nickel ferrite against phytopathogenic fungi is reported here. As a proof of concept, it is also shown how such nanoparticles can be used as fungicides in plants. The developed cobalt and nickel ferrite nanoparticles (CoFe2O4 and NiFe2O4) are successfully tested for antimycotic activity against three plant-pathogenic fungi: Fusarium oxysporum, Colletotrichum gloeosporioides, and Dematophora necatrix. In addition, it is also observed that these ferrite nanoparticles reduce the incidence of Fusarium wilt in capsicum. The study suggests that nanoparticles of CoFe2O4 and NiFe2O4 can be used as an effective fungicide in plant disease management.

The preprotein translocase YidC controls respiratory metabolism in Mycobacterium tuberculosis.

The YidC-Oxa1-Alb3 preprotein translocases play a vital role in membrane insertion of proteins in eukaryotes and bacteria. In a recent study we observed that Rv3921c, which encodes putative YidC translocase in Mycobacterium tuberculosis (Mtb), is essential for in vitro growth of bacteria. However, the exact function of this particular protein remains to identify in mycobacterial pathogens. By performing a systematic study here we show that YidC of Mtb is an envelope protein, which is required for production of ATP and maintenance of cellular redox balance. Drastic effects of depletion of Rv3921c on the expression of hypoxic genes, ATP synthases, and many proteins of central metabolic and respiratory pathways shed a significant light on the function of YidC towards controlling respiratory metabolism in Mtb. Association of YidC with proteins such as succinate dehydrogenases and ubiquinol-cytochrome C reductase further confirms its role in respiration. Finally we demonstrate that YidC is required for the intracellular survival of Mtb in human macrophages.