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111.
Yann C. Klimentidis Akshay Chougule Amit Arora Alexis C. Frazier-Wood Chiu-Hsieh Hsu 《PLoS genetics》2015,11(5)
Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2D, and the interaction of baseline TG with TG genetic risk on incident T2D in 13,247 European-Americans (EA) and 3,238 African-Americans (AA) from three prospective cohort studies. A TG genetic risk score (GRS) was calculated based on 31 validated single nucleotide polymorphisms (SNPs). We considered several baseline covariates, including body- mass index (BMI) and lipid traits. Among EA and AA, we find, as expected, that baseline levels of TG are strongly positively associated with incident T2D (p<2 x 10-10). However, the TG GRS is negatively associated with T2D (p=0.013), upon adjusting for only race, in the full dataset. Upon additionally adjusting for age, sex, BMI, high-density lipoprotein cholesterol and TG, the TG GRS is significantly and negatively associated with T2D incidence (p=7.0 x 10-8), with similar trends among both EA and AA. No single SNP appears to be driving this association. We also find a significant statistical interaction of the TG GRS with TG (pinteraction=3.3 x 10-4), whereby the association of TG with incident T2D is strongest among those with low genetic risk for TG. Further research is needed to understand the likely pleiotropic mechanisms underlying these findings, and to clarify the causal relationship between T2D and TG. 相似文献
112.
Avinash?SharmaEmail author Kunal?Jani Yogesh?S.?Shouche Anita?Pandey 《Annals of microbiology》2015,65(3):1323-1332
Bacterial diversity of the Soldhar hot spring, located in the Chamoli district of Uttarakhand, India, was investigated using a clone library, denaturing gradient gel electrophoresis (DGGE) and functional genes. Physicochemical analysis of sediment samples indicated an oligotrophic environment with very low sulfur content. Based on the 16S rRNA gene studies Proteobacteria was the most predominant group in all the three approaches. Other dominant phyla were Deinococcus-Thermus and Aquificae. Pyrobaculum was the only archaeal genus detected by DGGE. In the functional gene analysis, the nifH library showed a single operational taxonomic unit (OTU) related to the genus Paenibacillus whereas the aoxB library showed three OTUs related to Acidovorax, Aminobacter and Agrobacterium. Our results demonstrate for the first time both the bacterial and archaeal diversity in the Soldhar hot spring by culture-independent techniques, thereby providing important information that will increase our understanding of the microbial ecology of the Soldhar hot spring. 相似文献
113.
Jayant Arora John M Hickey Ranajoy Majumdar Reza Esfandiary Steven M Bishop Hardeep S Samra C Russell Middaugh David D Weis David B Volkin 《MABS-AUSTIN》2015,7(3):525-539
There is a need for new analytical approaches to better characterize the nature of the concentration-dependent, reversible self-association (RSA) of monoclonal antibodies (mAbs) directly, and with high resolution, when these proteins are formulated as highly concentrated solutions. In the work reported here, hydrogen exchange mass spectrometry (HX-MS) was used to define the concentration-dependent RSA interface, and to characterize the effects of association on the backbone dynamics of an IgG1 mAb (mAb-C). Dynamic light scattering, chemical cross-linking, and solution viscosity measurements were used to determine conditions that caused the RSA of mAb-C. A novel HX-MS experimental approach was then applied to directly monitor differences in local flexibility of mAb-C due to RSA at different protein concentrations in deuterated buffers. First, a stable formulation containing lyoprotectants that permitted freeze-drying of mAb-C at both 5 and 60 mg/mL was identified. Upon reconstitution with RSA-promoting deuterated solutions, the low vs. high protein concentration samples displayed different levels of solution viscosity (i.e., approx. 1 to 75 mPa.s). The reconstituted mAb-C samples were then analyzed by HX-MS. Two specific sequences covering complementarity-determining regions CDR2H and CDR2L (in the variable heavy and light chains, respectively) showed significant protection against deuterium uptake (i.e., decreased hydrogen exchange). These results define the major protein-protein interfaces associated with the concentration-dependent RSA of mAb-C. Surprisingly, certain peptide segments in the VH domain, the constant domain (CH2), and the hinge region (CH1-CH2 interface) concomitantly showed significant increases in local flexibility at high vs. low protein concentrations. These results indicate the presence of longer-range, distant dynamic coupling effects within mAb-C occurring upon RSA. 相似文献
114.
Introduction
Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART).Methods
Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR.Results
The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase(SHP)-1 and a reduced expression of positive regulators like Janus kinase(JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells.Conclusions
Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease, needs further investigation. The information may be useful in design of novel therapeutic targets for better management of disease. 相似文献115.
Syed G. Dastager Rahul Mawlankar Shan-Kun Tang Krishnamurthi Srinivasan V. Venkata Ramana Yogesh S. Shouche 《Antonie van Leeuwenhoek》2014,105(1):199-206
A novel bacterial strain, designated SGD-1123T was isolated from Chorao Island, in Goa Province, India. The strain was found to be able to grow at 15–42 °C, pH 5–12 and 0–12 % (w/v) NaCl. The whole cell hydrolysates were found to contain meso-diaminopimelic acid, galactose and arabinose. The major fatty acids were identified as iso-C15:0 and anteiso-C15:0, MK-7 was identified as the predominant menaquinone and the predominant polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified aminolipid. The genomic DNA G+C content was determined to be 44.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences placed the isolate within the genus Bacillus and further revealed that strain SGD-1123T had highest sequence similarity with Bacillus aquimaris, and forms a separate clade with its closest relatives i.e. B. aquimaris, Bacillus vietnamensis and Bacillus marisflavi, with which it shares 94.5, 94.1 and 94.1 % similarity respectively. The phylogenetic, chemotaxonomic and phenotypic analyses indicated that strain SGD-1123T represents a novel species within the genus Bacillus, for which the name Bacillus enclensis is proposed. The type strain is SGD-1123T (NCIM 5450T=CCTCC AB 2011125T). 相似文献
116.
117.
Meetu Gupta Andaleeb Sajid Kirti Sharma Soumitra Ghosh Gunjan Arora Ramandeep Singh Valakunja Nagaraja Vibha Tandon Yogendra Singh 《Journal of bacteriology》2014,196(14):2646-2657
HU, a widely conserved bacterial histone-like protein, regulates many genes, including those involved in stress response and virulence. Whereas ample data are available on HU-DNA communication, the knowledge on how HU perceives a signal and transmit it to DNA remains limited. In this study, we identify HupB, the HU homolog of the human pathogen Mycobacterium tuberculosis, as a component of serine/threonine protein kinase (STPK) signaling. HupB is extracted in its native state from the exponentially growing cells of M. tuberculosis H37Ra and is shown to be phosphorylated on both serine and threonine residues. The STPKs capable of modifying HupB are determined in vitro and the residues modified by the STPKs are identified for both in vivo and the in vitro proteins through mass spectrometry. Of the identified phosphosites, Thr65 and Thr74 in the DNA-embracing β-strand of the N-terminal domain of HupB (N-HupB) are shown to be crucial for its interaction with DNA. In addition, Arg55 is also identified as an important residue for N-HupB–DNA interaction. N-HupB is shown to have a diminished interaction with DNA after phosphorylation. Furthermore, hupB is shown to be maximally expressed during the stationary phase in M. tuberculosis H37Ra, while HupB kinases were found to be constitutively expressed (PknE and PknF) or most abundant during the exponential phase (PknB). In conclusion, HupB, a DNA-binding protein, with an ability to modulate chromatin structure is proposed to work in a growth-phase-dependent manner through its phosphorylation carried out by the mycobacterial STPKs. 相似文献
118.
Jain S Mythily S Ahmed RS Arora VK Banerjee BD 《Indian journal of biochemistry & biophysics》2010,47(6):388-392
The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with aconcomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histoarchitectural alterations at sub-chronic doses of triazophos in rats. 相似文献
119.
N. K. Arora Ekta Khare S. Singh D. K. Maheshwari 《World journal of microbiology & biotechnology》2010,26(5):811-816
Most of the legume crops are affected by metal stress present in the soil mainly due to contaminated agrochemicals and sewage
sludge. The effect of aluminium, and heavy metals copper, iron and molybdenum on growth and activity of enzymes of fast and
slow growing rhizobial sps. was studied. Sinorhizobium meliloti RMP5 was found to be more tolerant to metal stress than Bradyrhizobium BMP1. Both the strains were extremely sensitive to Al than other metals. Al was much more deleterious for the enzymatic activities
(nitrate reduction, nitrite reduction, nitrogenase and uptake hydrogenase) of strain RMP5 and BMP1. Cu showed inhibitory effect on growth and enzyme activities of Bradyrhizobium strain at all concentrations. However, in S. meliloti RMP5 all the tested enzymatic activities increased up to the concentration of 0.1 mM Cu. Fe enhanced the growth and enzyme activities
of S. meliloti RMP5 and Bradyrhizobium BMP1 up to 100 mM concentration. Mo enhanced all the tested enzymatic activities of S. meliloti RMP5 up to 1 mM. Nitrate and nitrite reduction activities of Bradyrhizobium BMP1 increased up to 1 mM concentration. However, nitrogenase and hydrogenase activities of Bradyrhizobium BMP1 got enhanced only up to 0.5 mM Mo. Both Fe and Mo are the key components of the enzyme nitrogenase and nitrate reductase
and enhanced the growth and enzyme activities of both the sps. The study of physiology of nitrogen fixing ability of both
fast and slow growing rhizobial strains reported that the supplementation of Mo and Fe in soils along with the biological
formulations will enhance the process of symbiotic nitrogen fixation. 相似文献
120.