A novel method for measuring protein kinase C activity in a native membrane-associated state

Physiological activation of protein kinase C (PKC) is believed to occur by redistributing soluble enzyme to the phospholipid environment of membranes. Currently available in vitro methods of measuring PKC activation all involve prior extraction of membrane-associated enzyme and its reconstitution in an artificial phospholipid environment or modification (such as partial trypsinization) of the enzyme itself. Here we report a novel method which, for the first time, allows measurement of active PKC still in its native, membrane-associated state using a specific, physiological substrate. Thus, with this new method PKC activity can be measured while still in an environment that approximates the in vivo situation.     

How long should angiotensin-converting enzyme inhibitors be given to patients following myocardial infarction: implications of the HOPE trial

Long-term treatment with angiotensin-converting enzyme inhibitors reduces post-infarction morbidity and mortality in patients with left ventricular (LV) systolic dysfunction or symptomatic heart failure. Until recently, the effect of such treatment in patients with preserved LV function has not been known. The results from the Heart Outcome Prevention Evaluation trial have indicated that long-term treatment with ramipril leads to a significant reduction in cardiovascular events in patients with atherosclerotic disease, including those with prior myocardial infarction and preserved LV function. These results suggest that long-term angiotensin-converting enzyme inhibition should also be considered in post-infarction patients with normal cardiac function.     

Changing trends in the outpatient dental visits during the COVID – 19 pandemic in a tertiary care hospital

The coronavirus pandemic has caused a global public health crisis with an unprecedented shutdown of major establishments and non-emergency services. Disruptions across the country in dental hospitals led to challenges in addressing patient’s dental complaints. The present study aimed to analyse the difference in the pattern of the Outpatient dental visits during the pandemic period in comparison to that of the pre-pandemic period in a tertiary care hospital. This retrospective study was carried out by retrieving the patient data from the diagnostic register of the Department of Oral Medicine and Radiology for a period of one year. The data that was retrieved from 24th September 2019 to 23rd March 2020 was categorized under the pre-pandemic period and the data from 24th March 2020 to 24th September 2020 was grouped under the pandemic period. Patient data regarding the age, gender and clinical diagnosis was recorded and categorized under three main categories: “Emergency”, “urgent” and “elective”. 7550 patients during pre-pandemic period and 4035 patients during the pandemic period visited the dental hospital during the study period. Under the “emergency dental care” category, during the pre-pandemic period, majority of the cases reported of acute dental pain (71.0%) followed by cellulitis and space infection (20.1%) and maxillofacial trauma (8.7%). During the pandemic period, acute dental pain consisted of all emergency visits (n = 307). The proportion of emergency dental visits during the pandemic were significantly higher than the pre-pandemic period. Elective dental visits were significantly higher during pre-pandemic period in comparison to the pandemic period. (P < 0.001). There was a notable change in the outpatient trend of the dental visits during the COVID-19 pandemic in comparison to the pre-pandemic period. Emergency dental services were utilized at a higher rate during the pandemic period in comparison to the pre-pandemic counterpart.     

The solution structures of higher-order human telomere G-quadruplex multimers

Human telomeres contain the repeat DNA sequence 5′-d(TTAGGG), with duplex regions that are several kilobases long terminating in a 3′ single-stranded overhang. The structure of the single-stranded overhang is not known with certainty, with disparate models proposed in the literature. We report here the results of an integrated structural biology approach that combines small-angle X-ray scattering, circular dichroism (CD), analytical ultracentrifugation, size-exclusion column chromatography and molecular dynamics simulations that provide the most detailed characterization to date of the structure of the telomeric overhang. We find that the single-stranded sequences 5′-d(TTAGGG)_n, with n = 8, 12 and 16, fold into multimeric structures containing the maximal number (2, 3 and 4, respectively) of contiguous G4 units with no long gaps between units. The G4 units are a mixture of hybrid-1 and hybrid-2 conformers. In the multimeric structures, G4 units interact, at least transiently, at the interfaces between units to produce distinctive CD signatures. Global fitting of our hydrodynamic and scattering data to a worm-like chain (WLC) model indicates that these multimeric G4 structures are semi-flexible, with a persistence length of ∼34 Å. Investigations of its flexibility using MD simulations reveal stacking, unstacking, and coiling movements, which yield unique sites for drug targeting.