Biophysical investigations on the active site of brain hexokinase

Replacement of Mg (II), the natural activator of brain hexokinase (EC 2.7.1.1) by paramagnetic Mn (II) without affecting the physiological properties of the enzyme, has rendered brain hexokinase accessible to investigations by magnetic resonance methods. Based on such studies, a site on the enzyme, where Mn (II) binds directly with high affinity has been identified and characterized in detail. Use of β,γ-bidentate Cr (III) ATP as an exchange-inert analogue for Mn (II) ATP has shown that Mn (II) binding directly to the enzyme has no catalytic role but another Mn (II) ion binding simultaneously and independently to the enzyme through the nucleotide bridge participates in enzyme function. However, using this direct binding Mn (II) ion and a covalently bound spin label as paramagnetic probes a beginning has been made in mapping the ligand binding sites of the enzyme. Ultra-violet difference spectroscopy has revealed the presence of at least two glucose 6-phosphate locations on the enzyme one of which presumably is the high affinity regulatory site modulated by substrate glucose. Elution behaviour of the enzyme on a phosphocellulose column suggests that glucose induces a specific phosphate site on the enzyme to which the phosphate bearing regulatory ligands of the enzyme may bind

Urbanization and Green Spaces—A Study on Jnana Bharathi Campus, Bangalore University

Global warming is amongst the most alarming problems of the new era. Carbon emission is evidently the strongest fundamental factor for global warming. So increasing carbon emission is one of today’s major concerns, which is well addressed in the Kyoto Protocol. Trees are amongst the most significant elements of any landscape, because of both biomass and diversity, and their key role in ecosystem dynamics is well known. Trees absorb the atmospheric carbon dioxide and act as a carbon sink, since 50 % of biomass is carbon itself and the importance of carbon sequestration in forest areas is already accepted, and well documented. With this background, a carbon sequestration potential study was carried out in Jnana Bharathi campus, Bangalore University using the Quadrat method. The total geographical area is about 449.74 ha with a rich vegetation sector and the total amount of both above ground carbon (AGC) and below ground carbon (BGC) was estimated as an average of 54.8 t/ha. The total amount of carbon dioxide assimilated into the vegetation in terms of both above ground and below ground biomass was estimated as an average of 200.9 t/ha. Urbanization and habitat fragmentation seem to be increasing worldwide, substantiated by a case study in Bangalore City. The analysis revealed that increase in built-up area at the city level was by about 164.62 km2, while the vegetation and water bodies decreased by about 285.72 and 7.2 km2 respectively. However, Bangalore University, Jnana Bharathi campus attains a good vegetation cover and is seen as one of the ‘green lungs’ of Bangalore city

Care management for Type 2 diabetes in the United States: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>This systematic review and meta-analysis aims at assessing the composition and performance of care management models evaluated in the last decade and their impact on patient important outcomes.</p> <p>Methods</p> <p>A comprehensive literature search of electronic bibliographic databases was performed to identify care management trials in type 2 diabetes. Random effects meta-analysis was used when feasible to pool outcome measures.</p> <p>Results</p> <p>Fifty-two studies were eligible. Most commonly reported were surrogate outcomes (such as HbA1c and LDL), followed by process measures (clinic visit or testing frequency). Less frequently reported were quality of life, patient satisfaction, self-care, and healthcare utilization. Most care management modalities were carved out from primary care. Meta-analysis demonstrated a statistically significant but trivial reduction of HbA1c (weighted difference in means -0.21%, 95% confidence interval -0.40 to -0.03, p < .03) and LDL-cholesterol (weighted difference in means -3.38 mg/dL, 95% confidence interval -6.27 to -0.49, p < .02).</p> <p>Conclusions</p> <p>Most care management programs for patients with type 2 diabetes are 'carved-out', accomplish limited effects on metabolic outcomes, and have unknown effects on patient important outcomes. Comparative effectiveness research of different models of care management is needed to inform the design of medical homes for patients with chronic conditions.</p

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

The special values of the standard LL-functions for GSp2n×GL1\mathrm{GSp}_{2n} \times \mathrm{GL}_1

This is the accepted version. To appear in Transactions of the American Mathematical SocietyWe prove the expected algebraicity property for the critical values of character twists of the standard $L$-function associated to vector-valued holomorphic Siegel cusp forms of archimedean type $(k_1, k_2, \ldots, k_n)$, where $k_n \geq n+1$ and all $k_i$ are of the same parity. For the proof, we use an explicit integral representation to reduce to arithmetic properties of differential operators on vector-valued nearly holomorphic Siegel cusp forms. We establish these properties via a representation-theoretic approach