Bistable dynamics of cardiac cell models coupled by dynamic gap junctions linked to Cardiac Memory

In an earlier study, we suggested that adaptive gap junctions (GJs) might be a basis of cardiac memory, a phenomenon which refers to persistent electrophysiological response of the heart to external pacing. Later, it was also shown that the proposed mechanism of adaptation of GJs is consistent with known electrophysiology of GJs. In the present article, we show that a pair of cardiac cell models coupled by dynamic, voltage-sensitive GJs exhibits bistable behavior under certain conditions. Three kinds of cell pairs are considered: (1) a Noble–Noble cell pair that represents adjacent cells in Purkinje network, (2) a pair of DiFranceso–Noble cells that represents adjacent SA nodal cells, and (3) a model of Noble cell coupled to Luo–Rudy cell model, which represents an interacting pair of a Purkinje fiber and a ventricular myocyte. Bistability is demonstrated in all the three cases. We suggest that this bistability might be an underlying factor behind cardiac memory. Focused analysis of a pair of Noble cell models showed that bistability is obtained only when the properties of GJs “match” with the properties of the pair of cells that is coupled by the GJs. This novel notion of match between GJs and cardiac cell types might give an insight into specialized distributions of various connexin proteins in cardiac tissue.     

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.     

Inappropriate defibrillator shock due to oversensing. What is the mechanism?

Implantable cardioverter defibrillator (ICD) is often advised for secondary prevention of sudden cardiac death. Inappropriate shocks from ICD is uncommon but can seriously affect the quality of life. One of the reasons for inappropriate ICD shock is loose set screw, which may remain undetected by device interrogation and/or fluoroscopy. A 55-year lady presented with multiple inappropriate shocks few hours after an ICD implantation. The discrepancy between near field (NF, tip to ring) and far field (FF, Can to RV coil) signals helped us to suspect noise related to loose set screw, as the underlying problem. Re-exploration of the pocket had to be performed as the last resort to confirm the diagnosis and rectify the problem.     

Cobalt (II) imprinted chitosan for selective removal of cobalt during nuclear reactor decontamination

The selectivity of chitosan has been modified through metal ion imprinting technique for its potential application in nuclear industry. Considerable reduction in radioactive waste volume, generated during the chemical decontamination of nuclear power plants, can be achieved through the selective removal of the radionuclides. In this context, a Co(II) imprinted chitosan was synthesized using epichlorohydrin as the crosslinker. The selective removal of Co(II) in presence of Fe(II), which is the major non-radioactive ion present in excess during decontamination, was studied. The imprinted chitosan showed selective sorption of Co(II) over Fe(II), while the raw chitosan was selective to Fe(II) over Co(II). The imprinted chitosan was found to retain the enhanced selectivity towards Co(II) under various solution conditions, including typical nuclear reactor decontamination formulations containing strong complexants. The highest uptake by the imprinted chitosan, with maximum selectivity for Co(II) over Fe(II), was obtained in citrate medium at pH 4.8.     

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.     

Consequences of adaptation to larval crowding on sexual and fecundity selection in Drosophila melanogaster

Sexual selection is a major force influencing the evolution of sexually reproducing species. Environmental factors such as larval density can manipulate adult condition and influence the direction and strength of sexual selection. While most studies on the influence of larval crowding on sexual selection are either correlational or single-generation manipulations, it is unclear how evolution under chronic larval crowding affects sexual selection. To answer this, we measured the strength of sexual selection on male and female Drosophila melanogaster that had evolved under chronic larval crowding for over 250 generations in the laboratory, along with their controls which had never experienced crowding, in a common garden high-density environment. We measured selection coefficients on male mating success and sex-specific reproductive success, as separate estimates allowed dissection of sex-specific effects. We show that experimental evolution under chronic larval crowding decreases the strength of sexual and fecundity selection in males but not in females, relative to populations experiencing crowding for the first time. The effect of larval crowding in reducing reproductive success is almost twice in females than in males. Our study highlights the importance of studying how evolution in a novel, stressful environment can shape adult fitness in organisms.