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921.
Robert L. Seymour Prashant V. Mishra M. Akbar Khan & Michael P. Spector 《Molecular microbiology》1996,20(3):497-505
The starvation-stress response (SSR) of Salmonella typhimurium encompasses the physiological changes that occur upon starvation for an essential nutrient, e.g. C-source. A subset of SSR genes, known as core SSR genes, are required for the long-term starvation survival of the bacteria. Four core SSR loci have been identified in S. typhimuriumrpoSstiAstiB, and stiC. Here we report that in S. typhimurium C-starvation induced a greater and more sustainable cross-resistance to oxidative challenge (15 mM hydrogen peroxide (H2O2) for 40 min) than either N- or P-starvation. Of the four core SSR loci, only rpoS and stiC mutants exhibited a defective C-starvation-inducible cross-resistance to H2O2 challenge. Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA mutants were very sensitive to oxidative challenge. Based on this, we determined if these core SSR loci were important for H2O2 resistance developed during a 60 min adaptive exposure to 60 μM H2O2 (adapted cells). Both unadapted and adapted rpoS and stiA mutants were hypersensitive to a H2O2 challenge. In addition, a stiB mutant exhibited normal adaptive resistance for the first 20 mins of H2O2 challenge but then rapidly lost viability, declining to a level of about 1.5% of the wild-type strain. The results of these experiments indicate that: (i) the rpoS and stiC loci are essential for the development of C-starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoSstiA, and, in a delayed effect, stiB loci are needed for H2O2-inducible adaptive resistance to oxidative challenge. Moreover, we found that both stiA and stiB are induced by a 60 μM H2O2 exposure, but only stiA was regulated (repressed) by (reduced form) OxyR. 相似文献
922.
Mohd Wajid Ali Khan Ahmed Al Otaibi Subuhi Sherwani Eida Mohammed Alshammari Salma Ahmed Al-Zahrani Wahid Ali Khan Abdulmohsen Khalaf Dhahi Alsukaibi Sultan Alouffi Shahper Nazeer Khan 《Bioinformation》2021,17(3):460
Human Vg9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients. Hence, optimization of methods needs to be carried out for the efficient expansion of these T cells. Standardization of peripheral blood mononuclear cells (PBMCs) isolation was devised. Cytokines (interleukin 2 (IL-2) and interleukin 15 (IL-15)) and zoledronate were also standardized for different concentrations. It was found that an increased number of PBMCs were recovered when washing was done at 1100 revolution per minute (rpm). Significantly high expansion fold was (2524 ± 787 expansion fold) achieved when stimulation of PBMCs was done with 1 µM of zoledronate and both cytokines IL-2 and IL-15 supported the expansion and survival of cells at the concentrations of 100 IU/ml and 10 ng/ml respectively. 14-day cultures showed highly pure (91.6 ± 5.1%) and live (96.5 ± 2.5%) expanded γδ T cells. This study aimed to standardize an easy to manipulate technique for the expansion of γδ T cells, giving a higher yield. 相似文献
923.
924.
The bioproduction of benzaldehyde from benzyl alcohol using Pichia pastoris was examined in a solid–liquid two-phase partitioning bioreactor (TPPB) to reduce substrate and product inhibition. Rational
polymer selection identified Elvax 40W as an effective sequestering phase, possessing partition coefficients for benzyl alcohol
and benzaldehyde of 3.5 and 35.4, respectively. The use of Elvax 40W increased the overall mass of benzaldehyde produced by
approx. 300% in a 5 l bioreactor, relative to a single phase biotransformation. The two-phase system had a molar yield of
0.99, indicating that only minor losses occurred. These results provide a promising starting point for solid–liquid TPPBs
to enhance benzaldehyde production, and suggest that multiple, targeted polymers may provide relief for transformations characterized
by multiple inhibitory substrates/product/by-products. 相似文献
925.
Lakshmi Kumar Tatini N. Someswara Rao Muzaffar Khan Krishna Sumanth Peraka K. V. S. R. Krishna Reddy 《AAPS PharmSciTech》2013,14(2):558-568
Three new solvates [mono-dimethyl sulfoxide (mono-DMSO), mono-dimethyl acetamide (mono-DMA) and mono-dimethyl formamide (mono-DMF)] of 10-Deacetyl baccatin III, were generated by slow evaporation in DMSO, DMF, and DMSO/DMA (1:1) solvent systems respectively. Two concomitant forms mono-DMSO(a new form) and di-DMSO (a known form) were obtained in the DMSO solvent system. Yet two other concomitant forms mono-DMA (a new form) and di-DMSO (a known form) were obtained in DMSO/DMA (1:1) solvent system. A fourth solvate mono-DMF (a new form) was crystallized in unimolar ratio using DMF as a solvent. These solvates were characterized using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis (TGA), and spectroscopic [13C solid-state nuclear magnetic spectroscopy, solution 1H NMR, and Fourier transform infrared] techniques. The interactions between host and guest molecules were elucitated by single-crystal X-ray diffraction data. In all the cases, guest molecules are connected to the host molecules by O–H···O hydrogen bonds. A remarkable difference in the desolvation onset temperatures of di- and mono-DMSO solvates was observed which was also featured by a corresponding weight loss during TGA analysis. 相似文献
926.
Michael R. Heaven Anthony W. Herren Daniel L. Flint Natasha L. Pacheco Jiangtao Li Alice Tang Fatima Khan James E. Goldman Brett S. Phinney Michelle L. Olsen 《Molecular & cellular proteomics : MCP》2022,21(1):100180
Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice. 相似文献
927.
928.
929.
930.
Hina N. Khan Aldo Jongejan Lonneke A. van Vught Janneke Horn Marcus J. Schultz Aeilko H. Zwinderman Olaf L. Cremer Marc J. Bonten Tom van der Poll Brendon P. Scicluna 《Journal of cellular and molecular medicine》2021,25(16):7621-7630
Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways. 相似文献