The single polypeptide restriction–modification enzyme LlaGI is a self-contained molecular motor that translocates DNA loops

To cleave DNA, the single polypeptide restriction–modification enzyme LlaGI must communicate between a pair of indirectly repeated recognition sites. We demonstrate that this communication occurs by a 1-dimensional route, namely unidirectional dsDNA loop translocation rightward of the specific recognition sequence 5′-CTnGAyG-3′ as written (where n is either A, G, C or T and y is either C or T). Motion across thousands of base pairs is catalysed by the helicase domain and requires the hydrolysis of 1.5-2 ATP per base pair. DNA loop extrusion is accompanied by changes in DNA twist consistent with the motor following the helical pitch of the polynucleotide track. LlaGI is therefore an example of a polypeptide that is a completely self-contained, multi-functional molecular machine

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

Highlights of the DNA cutters:a short history of the restriction enzymes

In the early 1950’s, ‘host-controlled variation in bacterial viruses’ was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine

PyTensor: A Python based Tensor Library

Multi-dimensional (or multi-way) analysis have evinced considerable interest within the datamining community. In this technical report, we describe the development and implementation of a python based library to perform multi-way analysis. Our results show that the python implementation runs comparable to the MATLAB implementation. The implementation is available from http://pytensor.googlecode.com/

Budding adult hypertensives with modifiable risk factors: "Catch them young"

Background: Since the data of primary hypertension (HT) in children is scanty in India, this study attempted to evaluate HT by a multidimensional investigation of the various risk factors in children and adolescents. Materials and Methods: A total of 3906 subjects were recruited, all of whom lived in Chennai, an urban area of Tamil Nadu. The children and adolescents aged from 10 to 17 years were selected by random sampling. The children/adolescents were randomized into one control and further divided into two groups. The National High Blood Pressure Education Program fourth report (2004) and anthropometric body mass index (BMI), food frequency questionnaire (PURE) were followed in the study. Results: Out of 3906 children, 2107 were girls and 1799 boys. On screening, we found 9.5% to be hypertensive with the prevalence rate of boys and girls 8% and 10.8%, respectively. Overall obesity was 2.7%, (boys 2%, girls 3.32%); hypertensives and normotensives were 8.4% and 2.1%, respectively. We found that overweight (odds ratio [OR]: 2.06 [1.40-3.01] 95% confidence interval [CI]), obese children (OR: 1.21 [2.72-6.48] 95% CI), and those with a family history of HT (OR: 1.66 [1.20-2.30] 95% CI) had increased risk of hypertension. Females were 1.39 times (OR: 1.39 [1.11-1.72] 95% CI) more at risk of getting HT. Multivariate analysis showed that obese children/adolescent were four times more likely to have HT than children with normal BMI (OR: 4.67 [3.00-7.26] 95% CI]. Conclusion: Family history of HT, obesity, and female gender are associated with a high risk of HT. The prevalence of HT was higher among obese adolescents than among slender subjects. This may be related to their sedentary lifestyle, faulty eating habits, high fat content in the diet and little physical activity