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Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks. We applied a numerical rare-event sampling algorithm to study transition paths of spontaneous noise-induced switching for a ubiquitous gene regulatory network motif, the bistable toggle switch, in which two mutually repressive genes compete for dominant expression. We find that the method can efficiently uncover detailed switching mechanisms that involve fluctuations both in occupancies of DNA regulatory sites and copy numbers of protein products. In addition, we show that the rate parameters governing binding and unbinding of regulatory proteins to DNA strongly influence the switching mechanism. In a regime of slow DNA-binding/unbinding kinetics, spontaneous switching occurs relatively frequently and is driven primarily by fluctuations in DNA-site occupancies. In contrast, in a regime of fast DNA-binding/unbinding kinetics, switching occurs rarely and is driven by fluctuations in levels of expressed protein. Our results demonstrate how spontaneous cell phenotype transitions involve collective behavior of both regulatory proteins and DNA. Computational approaches capable of simulating dynamics over many system variables are thus well suited to exploring dynamic mechanisms in gene networks.

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

The microscopic details of how peptides translocate one at a time through nanopores are crucial determinants for transport through membrane pores and important in developing nano-technologies. To date, the translocation process has been too fast relative to the resolution of the single molecule techniques that sought to detect its milestones. Using pH-tuned single-molecule electrophysiology and molecular dynamics simulations, we demonstrate how peptide passage through the α-hemolysin protein can be sufficiently slowed down to observe intermediate single-peptide sub-states associated to distinct structural milestones along the pore, and how to control residence time, direction and the sequence of spatio-temporal state-to-state dynamics of a single peptide. Molecular dynamics simulations of peptide translocation reveal the time- dependent ordering of intermediate structures of the translocating peptide inside the pore at atomic resolution. Calculations of the expected current ratios of the different pore-blocking microstates and their time sequencing are in accord with the recorded current traces.

Introduction: The study aims to assess the procedural outcomes and follow-up after transcatheter closure of ventricular septal defects (VSDs) in children utilizing the Konar-MF™ occluder (Lifetech Scientific, Shenzhen, PRC) device. Materials and Methods: Clinical features, demographic characteristics, and follow-up findings of children undergoing percutaneous VSD device closure were retrospectively analyzed from the medical records. Results: Fifty-seven patients underwent VSD closure using the Konar-MF occluder between January 2019 and April 2023. Median age and body weight of patients were 36 (5-216) months and 12.5 (3.8-42) kg, respectively. The mean size of the defect on the left ventricular side was 6.5 ± 2.4 mm on echocardiography; the mean pulmonary artery pressure was 19.1 ± 9.7 mmHg. Three patients with severe pulmonary hypertension had successful device closure. The most used device size was 8 mm x 6 mm. The initially chosen device was upsized in 4 (7.01%) patients and downsized in 1 (1.7%) patient. Forty-five patients (78.9%) had device closure through the retrograde route. The procedure was successful in 53 (93.0%) patients. Immediate shunt occlusion was achieved in 86.8% of patients. Major complications, namely, embolization (1) and moderate aortic regurgitation (1) in two patients were successfully managed by surgery. One patient with severe tricuspid regurgitation has been on close follow-up. There was no mortality. Late complications such as valve regurgitation or rhythm disturbance were not identified on a median follow-up of 6 (1.5-47) months. Conclusion: Transcatheter VSD closure using a Konar-MF occluder device is safe and effective, even in smaller children. The ability to deliver both anterogradely and retrogradely is a unique advantage. [ABSTRACT FROM AUTHOR]

Unilateral absence of pulmonary artery (UAPA) can be either isolated or associated with other congenital cardiac defects. It is a rare congenital lesion with a diverse clinical presentation. We present a case of absent right pulmonary artery and large patent ductus arteriosus (PDA) with severe unilateral pulmonary hypertension. We describe our strategy of staged ductus arteriosus closure in this patient and successful outcome on long term follow up. [ABSTRACT FROM AUTHOR]

The left brachiocephalic vein (LBCV) usually passes superior and anterior to the aortic arch. In rare cases, this vein follows an anomalous course. We present a case of duplicated circumaortic LBCV in a 10-year-old child with Tetralogy of Fallot. [ABSTRACT FROM AUTHOR]

Transcatheter closure of patent ductus arteriosus (PDA) is now the standard of care with some exceptions. Best treatment for peripheral pulmonary artery (PA) stenosis in small children is still debatable. Surgical augmentation, balloon dilatation, and stenting are the available options with each having its own risks and limitations. Here, we are reporting complete transcatheter management of three cases of congenital rubella syndrome who had PDA and left branch PA stenosis by device closure and stent placement, with successful outcome in two cases and complication, leading to surgery in one. We also share our understanding of case selection for a better outcome. [ABSTRACT FROM AUTHOR]

Byline: Mahua. Roy, Jagabandhu. Ghosh, Sujit. Deb, Narayan. Pandit Ophthalmoplegic migraine (OM) is characterized by recurrent attacks of headache with paresis of ocular cranial nerves. Previously, it was classified as [...]

Byline: J. Ghosh, Mahua. Roy, Kalyan. Lahiri, A. Bala, Mahua. Roy Two clinical forms of rabies are recognize: i) a furious form associated with classical signs of excitation or phobic [...]

Syncretism is a well known phenomenon which bears the meaning of merging, melding and mixing different things to form a new concept. The concept of the term is very old and broadly used in different areas such as religion and culture. The function of syncretism is not only mixing or merging but also adopting different things and establishing link or bridge between similar things. Indian Classical Music is deeply influenced by the raga music as it is considered as the backbone of classical music. Raga has a wide history of its evolution that covers different dimensions. Syncretism plays a significant role in the evolution of raga ,as it has undergone various changes and reached at today's position .In this article it will my endeavor to cover the areas of evolution of raga on the basis of syncretism. [ABSTRACT FROM AUTHOR]