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71.
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Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They
can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards
identifying all potential replication origins in a 73-kb region of the long arm of fission yeast chromosome II, we have mapped
five new ARS elements using systematic subcloning and transformation assay. 2D analysis of one of the ARS plasmids that showed
highest transformation frequency localized the replication origin activity within the cloned genomic DNA. All the new ARS
elements are localized in two clusters in centromere proximal 40 kb of the region. The presence of at least six ARS elements,
including the previously reported ars727, is suggestive of a higher origin density in this region than that predicted earlier using a computer based search. 相似文献
74.
Roy S Khanna V Mittra S Dhar A Singh S Mahajan DC Priyadarsiny P Davis JA Sattigeri J Saini KS Bansal VS 《Life sciences》2007,81(1):72-79
Thiazolidinediones (TZDs) are currently the most efficacious class of oral antidiabetics. However, they carry the burden of weight gain and haemodilution, which may lead to cardiovascular complications. The present study was designed to ascertain whether a combination of dipeptidyl peptidase IV (DPP IV) inhibitor with low dose of a thiazolidinedione absolves TZD associated weight gain and oedema without compromising its efficacy. In this study, we examined the efficacy and safety of lower dose (1 mg/kg/day) of rosiglitazone, a thiazolidinedione, in combination with 5 mg/kg/day dose of LAF-237 (vildagliptin), a known DPP IV inhibitor, in aged db/db mice after 14 days of treatment and compared the combination with therapeutic dose (10 mg/kg) of rosiglitazone. The combination therapy showed similar efficacy as that of 10 mg/kg/day rosiglitazone in lowering random blood glucose (53.8%, p<0.001 and 54.3%, p<0.001 respectively), AUC ((0-120) min) during oral glucose tolerance test (OGTT) (38.6 %, p<0.01; 38.3%, p<0.01 respectively) and triglyceride levels (63.9% and 61% respectively; p<0.01). Plasma active glucagon like peptide-1 (GLP-1) and insulin levels were found to be elevated significantly (p<0.01 and p<0.05 respectively) in both LAF-237 and combination treated groups following oral glucose load. LAF-237 alone had no effect on random glucose and glucose excursion during OGTT in severely diabetic db/db mice. Interestingly, the combination treatment showed no significant increase in body weight as compared to the robust weight gain by therapeutic dose of rosiglitazone. Rosiglitazone at 10 mg/kg/day showed significant reduction (p<0.05) in haematocrit, RBC count, haemoglobin pointing towards haemodilution associated with increased mRNA expression of Na(+), K(+)-ATPase-alpha and epithelial sodium channel gamma (ENaCgamma) in kidney. The combination therapy escaped these adverse effects. The results suggest that combination of DPP IV inhibitor with low dose of thiazolidinedione can interact synergistically to represent a therapeutic advantage for the clinical treatment of type 2 diabetes without the adverse effects of haemodilution and weight gain associated with thiazolidinediones. 相似文献
75.
The role of mitochondria in causing diseases is becoming evident as more and more studies are focusing on this organelle of
the cell. This is largely attributed to its reactive oxygen species (ROS) production property. In the context of diabetes,
ROS is suggested to trigger different forms of insulin resistance involving different mechanisms. The suggestive role of a
mtDNA variant G10398A in increasing ROS production and the impaired response to oxidative stress due to T16189C variant is
worth addressing as genetic susceptibility factors in type 2 diabetes mellitus (T2DM). A case control study on 312 T2DM cases
and ethnically matched 466 controls involving two North Indian populations, referred as cohort 1 and cohort 2 (in a replicative
study), was undertaken to test such a genetic association. A statistically significant association was observed for 10398A
allele in both the cohorts [cohort1 (OR = 2.67 95% CI 1.77–4.00); cohort2 (OR = 1.76 95%CI 1.12–2.77)]. The analysis of G10398A/T16189C
haplotypic combinations revealed that 10398A/16189C haplotype provides a risk in both the cohorts. To sum up the study suggests
that 10398A and 16189C alleles provide susceptiblity to T2DM independently as well as together. 相似文献
76.
Rudimentary studies on aspects of biochemistry in India date back to 1927. But, in the field of Immunology, such studies were started by scholars only during early 1970s at the All India Institute of Medical Sciences, New Delhi, India. Science and Technology was not an immediate priority until 1961 due to domestic and political conditions in the country. We were then 11 years old since independence and our focus was on economic and social developments. Gradually, improvements were made in the field and now we have 15 to 20 major groups (small in size) of immunologists in the country, who have made significant contribution in the field during the last 8 to 10 years. Hence, we anticipate improvements in manpower and infrastructure in the near future. 相似文献
77.
Melanie J Carvell Phil J Marsh Shanta J Persaud Peter M Jones 《Cellular physiology and biochemistry》2007,20(5):617-626
Islet function is dependent on cells within the islet interacting with each other. E-cadherin (ECAD) mediates Ca(2+)-dependent homophilic cell adhesion between b-cells within islets and has been identified as a tumour suppressor. We generated clones of the MIN6 beta-cell line that stably over- (S) and under-express (alphaS) ECAD. Modified expression of ECAD was confirmed by quantitative RT-PCR, immunoblotting and immunocytochemistry. Preproinsulin mRNA, insulin content and basal rates of insulin secretion were higher in S cells compared to aS and control (V) cells. However, stimulated insulin secretory responses were unaffected by ECAD expression levels. ECAD expression did affect proliferation, with enhanced ECAD expression being associated with reduced proliferation and vice versa. Formation of islet-like structures was associated with a significant reduction in proliferation of V and S cells but not alphaS cells. These data suggest that ECAD expression levels do not modulate insulin secretory function but are consistent with a role for ECAD in the regulation of beta-cell proliferation. 相似文献
78.
Persaud SJ Muller D Belin VD Papadimitriou A Huang GC Amiel SA Jones PM 《Archives of physiology and biochemistry》2007,113(3):104-109
Arachidonic acid (AA) is generated in pancreatic beta-cells through the activation of Ca2+-dependent cytosolic phospholipase A2 (cPLA2) and the consequent hydrolysis of membrane phospholipids in the sn-2 position of the glycerophospholipid backbone. AA acts as a second messenger in beta-cells to elevate cytosolic Ca2+ levels and stimulate insulin secretion, but it is not clear whether these are direct effects of AA or are dependent on its metabolism by cyclooxygenase (COX) and/or lipoxygenase (LOX) enzymes. In addition, much of the published data in this area have been generated using insulin-secreting cell lines or rodent islets, with very little information on AA generation and metabolism in human islets of Langerhans. This short review examines cPLA2, COX and LOX expression and function in insulin- secreting cell lines and rodent and human islets. 相似文献
79.
Necessary and sufficient factors for the import of transfer RNA into the kinetoplast mitochondrion 总被引:1,自引:0,他引:1
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The mechanism of active transport of transfer RNA (tRNA) across membranes is largely unknown. Factors mediating the import of tRNA into the kinetoplast mitochondrion of the protozoon Leishmania tropica are organized into a multiprotein RNA import complex (RIC) at the inner membrane. Here, we present the complete characterization of the identities and functions of the subunits of this complex. The complex contains three mitochondrion- and eight nuclear-encoded subunits; six of the latter are necessary and sufficient for import. Antisense-mediated knockdown of essential subunits resulted in the depletion of mitochondrial tRNAs and inhibition of organellar translation. Functional complexes were reconstituted with recombinant subunits expressed in Escherichia coli. Several essential RIC subunits are identical to specific subunits of respiratory complexes. These findings provide new information on the evolution of tRNA import and the foundation for detailed structural and mechanistic studies. 相似文献
80.
Vibha Pandey Yogeshwar Vikram Dhar Parul Gupta Sumit K Bag Neelam Atri Mehar Hasan Asif Prabodh Kumar Trivedi Pratibha Misra 《BMC bioinformatics》2015,16(1)