Lactobacillus acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses in Human Intestinal Epithelial Cells

Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h) of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05), compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA) or its culture supernatant (CS), followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s) in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.     

Genomic annotation and validation of bacterial consortium NDMC-1 for enhanced degradation of sugarcane bagasse

This study aims at designing a consortium using rumen bacterial isolates for enhancing the hydrolysis of sugarcane bagasse (SB) for efficient biofuel formation. The microbial population was screened through biochemical and molecular tools along with enzymatic activity to obtain potential isolates for diverse cellulolytic and hemicellulolytic carbohydrate active enzyme (CAZyme). Five strains (Paenibacillus, Bacillus, Enterobacter, and Microbacterium) were selected for designing the consortium NDMC-1. The hydrolytic efficiency of NDMC-1 was determined based on cellulase production with simultaneous rise in monosaccharides, oligosaccharides, and soluble chemical oxygen demand (sCOD) concentration. Cellulolytic machinery of these isolates was further explored using genome sequencing. The isolates selected for consortia NDMC-1 interacted synergistically leading to enhanced cellulase production. Maximal endoglucanase (1.67 μmol ml−1 min−1), exoglucanase (0.69 μmol ml−1 min−1), and β-glucosidase (2.03 μmol ml−1 min−1) activity were achieved with SB as a sole carbon source after 48 h of incubation. Enhancement in SB hydrolysis employing NDMC-1 was evident by the increase in sCOD from 609 to 2589 mg/l and release of 1295 mg/l reducing sugar, comprising 59.8%, 8.23%, and 6.16% of glucose, cellobiose, and cellotriose, respectively, which resulted in 5.5-fold rise in biogas production. On genome annotation, total 472 contigs from glycoside hydrolase family: 84 from Microbacterium arborescens ND21, 72 from Enterobacter cloacae ND22, 61 from Bacillus subtilis ND23, 116 from Paenibacillus polymyxa ND24, and 140 from Paenibacillus polymyxa ND25 were identified. On further analysis, total 33 cellulases, 59 hemicellulases, and 48 esterases were annotated in the reported genomes. This work proposes the application of consortia-based bioprocessing systems over the conventionally favorable single organism approach for efficient hydrolysis of cellulosic substrates to fermentable sugars.     

Sterol methyltransferase is required for optimal mitochondrial function and virulence in Leishmania major

Limited knowledge on the exact functions of ergostane‐based sterols has hampered the application of sterol synthesis inhibitors against trypanosomatid parasites. Sterol methyltransferase (SMT) is directly involved in the synthesis of parasite‐specific C24‐methylated sterols, including ergosterol and 5‐dehydroepisterol. While pharmacological studies hint at its potential as a drug target against trypanosomatids, direct evidence for the cellular function and essentiality of SMT is lacking. Here, we characterized the SMT knockout mutants and their complemented strains in Leishmania major, the causative agent for cutaneous leishmaniasis. Deletion of SMT alleles led to a complete loss of C24‐methylated sterols, which were replaced by cholestane‐based sterols. SMT‐null mutants were fully viable and replicative in culture but showed increased sensitivity to sphingolipid synthesis inhibition. They were not particularly vulnerable to heat, acidic pH, nitrosative or oxidative stress, yet exhibited high mitochondrial membrane potential and increased superoxide generation indicating altered physiology of the mitochondria. Despite possessing high levels of GPI‐anchored glycoconjugates, SMT‐null mutants showed significantly attenuated virulence in mice. In total, our study reveals that the biosynthesis of ergostane‐based sterols is crucial for the proper function of mitochondria and the proliferation of Leishmania parasites in mammals.     

Spatial pattern of freshwater habitats and their prioritization using additive partitions of beta diversity of inhabitant piscine assemblages in the Terai–Dooars ecoregion of Eastern Himalayas

Limnology - Underlying spatial and habitat attributes of a river network are crucial to comprehend the bio-spatial arrangements within it, the study of which suffers from a paucity of information....     

Metagenomic insights into the environmental adaptation and metabolism of Candidatus Haloplasmatales,one archaeal order thriving in saline lakes

The KTK 4A-related Thermoplasmata thrives in the sediment of saline lakes; however, systematic research on its taxonomy, environmental adaptation and metabolism is lacking. Here, we detected this abundant lineage in the sediment of five artificially separated ponds (salinity 7.0%–33.0%) within a Chinese soda-saline lake using culture-independent metagenomics and archaeal 16S rRNA gene amplicons. The phylogenies based on the 16S rRNA gene, and 122 archaeal ubiquitous single-copy proteins and genome-level identity analyses among the metagenome-assembled genomes demonstrate this lineage forming a novel order, Candidatus Haloplasmatales, comprising four genera affiliated with the identical family. Isoelectric point profiles of predicted proteomes suggest that most members adopt the energetically favourable ‘salt-in’ strategy. Functional prediction indicates the lithoheterotrophic nature with the versatile metabolic potentials for carbohydrate and organic acids as well as carbon monoxide and hydrogen utilization. Additionally, hydrogenase genes hdrABC-mvhADG are linked with incomplete reductive citrate cycle genes in the genomes, suggesting their functional connection. Comparison with the coupling of HdrABC-MvhADG and methanogenesis pathway provides new insights into the compatibility of laterally acquired methanogenesis with energy metabolism in the related order Methanomassiliicoccales. Globally, our research sheds light on the taxonomy, environmental adaptative mechanisms, metabolic potentials and evolutional significance of Ca. Haloplasmatales.     

Data mining of transcriptional biomarkers at different cotton fiber developmental stages

Functional & Integrative Genomics - Advancement of the gene expression study provides comprehensive information on pivotal genes at different cotton fiber development stages. For the betterment...     

Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors

The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-d-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of l-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.