MtnK, methylthioribose kinase, is a starvation-induced protein in Bacillus subtilis

Background  

Methylthioadenosine, the main by-product of spermidine synthesis, is degraded inBacillus subtilisas adenine and methylthioribose. The latter is an excellent sulfur source and the precursor of quorum-sensing signalling molecules. Nothing was known about methylthioribose recycling in this organism.     

Inducible cytochrome P450 activities in renal glomerular mesangial cells: biochemical basis for antagonistic interactions among nephrocarcinogenic polycyclic aromatic hydrocarbons

BACKGROUND: Benzo(a)pyrene (BaP), anthracene (ANTH) and chrysene (CHRY) are polynuclear aromatic hydrocarbons (PAHs) implicated in renal toxicity and carcinogenesis. These PAHs elicit cell type-specific effects that help predict toxicity outcomes in vitro and in vivo. While BaP and ANTH selectively injure glomerular mesangial cells, and CHRY targets cortico-tubular epithelial cells, binary or ternary mixtures of these hydrocarbons markedly reduce the overall cytotoxic potential of individual hydrocarbons. METHODS: To study the biochemical basis of these antagonistic interactions, renal glomerular mesangial cells were challenged with BaP alone (0.03 - 30 microM) or in the presence of ANTH (3 microM) or CHRY (3 microM) for 24 hr. Total RNA and protein will be harvested for Northern analysis and measurements of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activity, respectively, to evaluate cytochrome P450 mRNA and protein inducibility. Cellular hydrocarbon uptake and metabolic profiles of PAHs were analyzed by high performance liquid chromatography (HPLC). RESULTS: Combined hydrocarbon treatments did not influence the cellular uptake of individual hydrocarbons. ANTH or CHRY strongly repressed BaP-inducible cytochrome P450 mRNA and protein expression, and markedly inhibited oxidative BaP metabolism. CONCLUSION: These findings indicate that antagonistic interactions among nephrocarcinogenic PAHs involve altered expression of cytochrome P450s that modulate bioactivation profiles and nephrotoxic/ nephrocarcinogenic potential.     

Intensive cannibalism and feeding on bregmacerotids in <Emphasis Type="Italic">Champsodon snyderi</Emphasis> (Champsodontidae): evidence for pelagic predation

Analysis of the stomach contents of 1002 specimens of Champsodon snyderi (Champsodontidae) (17.3–91.2mm SL) from Tosa Bay, southern Japan, showed that species to primarily feed on crustaceans and fishes (87.9% by frequency, 37.6% by weight for the former; 17.3% and 60.7% for the latter, respectively), although fishes occurred more often in stomachs of individuals larger than 50mm SL. Champsodon snyderi ingested large prey fishes (60.5–101.0% of predator SL), the maximum weight recorded for a single ingested specimen being 50.9% of the predator weight. Mesopelagic Bregmaceros nectabanus were by far the dominant prey fish, followed by C. snyderi (cannibalism), indicating that C. snyderi leaves the bottom to feed in the pelagic environment during the night.     

Two-step sequential optimization for production of ionic liquid stable cellulase from Bacillus subtilis I-2

The cost-effective bulk production of cellulases with desirable characteristics e.g., ionic liquid (IL)-stability, thermal, and pH stability is highly desirable. This study reports the optimization of cultural and environmental variables for enhanced production of an IL-stable, broad pH range, and thermo-stable cellulase from Bacillus subtilis I-2 employing low-cost agro-industrial wastes. Furthermore, combined interactive effects of different variables on enzyme yield were investigated using response surface methodology. The optimal levels of carbon and nitrogen sources were determined (% w/v, wheat bran 2.0, potato peel 1.5, cotton seed cake 0.8, and soybean meal 0.8) for enhanced cellulase yield. Further, optimization of environmental variables (temperature 48.41?°C, pH 7.0, and agitation rate 180 rpm) lead to overall 4.1-fold (76– 315.90 U/ml) enhancement of cellulase yield.     

1H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using ¹H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein-dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.     

Description of Distorhabditis poonchiana n. gen., n. sp. (Nematoda: Rhabditidae) from Jammu and Kashmir,India

Distorhabditis poonchiana n. gen., n. sp. from humus in Jammu and Kashmir, India, is described and illustrated. The new genus is characterized by a small body; slightly setoff labial region; long tubular gymnostom; prominently cuticularized cheilostom; absence of glottoid apparatus; monoprodelphic reproductive system; vulva (V) = 81 to 84; spicules with trifurcated distal ends, simple gubernaculum, peloderan bursa with eight pairs of bursal papillae arranged in 1 + 1 + 1 + 2 + 1 + 2 arrangement.     

Hematological profiles of COVID-19 patients at the Ratlam district,Madhya Pradesh State,India

It is of interest to compare the hematological profile (using Complete blood count) of COVID patients admitted in ICU, private ward, and isolation ward with varying severity. This data will help predict the severity of infection at peripheries and rural areas.  Detailed history and CBC was performed for all the cases. Different ratios and indexes such as systemic inflammatory index (SII), Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) were assessed. A total of 862 cases with a mean age of 49.9 ±17.4 years were enrolled. Hemoglobin level, lymphocyte (count per liter and percentage) were significantly lower in patients admitted in ICU as compared to patients admitted in the isolation ward and private ward (p <0.05). However, TLC, neutrophils, platelet count were higher in patients admitted to ICU (p <0.05). The Various ratios such as SII, NLR, and PLR showed significantly higher value in cases admitted in ICU (p <0.05). The TLC, neutrophil count, neutrophil percentage, SII, NLR, and PLR were significant predictors of severe disease (admission in ICU) with high diagnostic accuracy. We show that complete blood count method is a simple, readily available, rapid, and inexpensive tool that can be utilized for diagnosis and can predicting the severity of COVID 19 where RTPCR or trained staff is not available. Thus, NLR (%), SII, PLR, and TLC can predict severe illness with high accuracy.     

A modular map of Bradykinin-mediated inflammatory signaling network

Bradykinin, a member of the kallikrein-kinin system (KKS), is associated with an inflammatory response pathway with diverse vascular permeability functions, including thrombosis and blood coagulation. In majority, bradykinin signals through Bradykinin Receptor B2 (B2R). B2R is a G protein-coupled receptor (GPCR) coupled to G protein family such as Gα_qs, Gα_q/Gα_11, Gα_i1, and Gβ1_γ2_. B2R stimulation leads to the activation of a signaling cascade of downstream molecules such as phospholipases, protein kinase C, Ras/Raf-1/MAPK, and PI3K/AKT and secondary messengers such as inositol-1,4,5-trisphosphate, diacylglycerol and Ca²⁺ ions. These secondary messengers modulate the production of nitric oxide or prostaglandins. Bradykinin-mediated signaling is implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. Despite the biomedical importance of bradykinin, a resource of bradykinin-mediated signaling pathway is currently not available. Here, we developed a pathway resource of signaling events mediated by bradykinin. By employing data mining strategies in the published literature, we describe an integrated pathway reaction map of bradykinin consisting of 233 reactions. Bradykinin signaling pathway events included 25 enzyme catalysis reactions, 12 translocations, 83 activation/inhibition reactions, 11 molecular associations, 45 protein expression and 57 gene regulation events. The pathway map is made publicly available on the WikiPathways Database with the ID URL: https://www.wikipathways.org/index.php/Pathway:WP5132. The bradykinin-mediated signaling pathway map will facilitate the identification of novel candidates as therapeutic targets for diseases associated with dysregulated bradykinin signaling.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00652-0.     

Immune modulation by dendritic-cell-based cancer vaccines

The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour microenvironment or by revitalizing the immune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review, current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines are discussed. Some of the DC-based vaccines under clinical trials for various cancer types are highlighted. Establishing tumour immunity involves a plethora of immune components and pathways; hence, combining chemotherapy, radiation therapy and various arms of immunotherapy, after analysing the benefits of individual therapeutic agents, might be beneficial to the patient.