Tensor-SqRA: Modeling the transition rates of interacting molecular systems in terms of potential energies.

Estimating the rate of rare conformational changes in molecular systems is one of the goals of molecular dynamics simulations. In the past few decades, a lot of progress has been done in data-based approaches toward this problem. In contrast, model-based methods, such as the Square Root Approximation (SqRA), directly derive these quantities from the potential energy functions. In this article, we demonstrate how the SqRA formalism naturally blends with the tensor structure obtained by coupling multiple systems, resulting in the tensor-based Square Root Approximation (tSqRA). It enables efficient treatment of high-dimensional systems using the SqRA and provides an algebraic expression of the impact of coupling energies between molecular subsystems. Based on the tSqRA, we also develop the projected rate estimation, a hybrid data-model-based algorithm that efficiently estimates the slowest rates for coupled systems. In addition, we investigate the possibility of integrating low-rank approximations within this framework to maximize the potential of the tSqRA.

Protective effects of curcumin against traumatic brain injury.

Neuroinflammation is a key pathophysiological mechanism implicated in the neurodegenerative condition. One such condition implicating neuroinflammation is traumatic brain injury (TBI). Over the past decades, various alternative natural compounds, such as curcumin, have been investigated as novel therapeutic options to mitigate the pathophysiological pathways and clinical sequelae involved in TBI. As the main component of turmeric (Curcuma longa), curcumin has a broad range of clinical properties due to its considerable antioxidative and anti-inflammatory actions. This review discusses the pleiotropic mechanisms, the side effects, curcumin's delivery to the central nervous system (CNS), and its immunomodulatory and protective effects on TBI. Clinical trials, in vivo, and in vitro studies were extracted from different scientific databases, including PubMed, Scopus, and Google Scholar, to assess the effects of curcumin or its derivatives in TBI. Findings reveal that curcumin exhibited some protective effects on TBI via modulation of cell signaling pathways including toll-like receptor-4 (TLR-4), nuclear factor kappa B (NF-κB), and Nod-like receptor family proteins (NLRPs). Moreover, curcumin upregulates the brain-derived Neurotrophic Factor/Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2), which have crucial functions in modulation of TBI pathophysiological-mediated pathways. Curcumin displays beneficial immunomodulatory functions and protective capacities in different TBI models, although more clinical experiments are required to clarify curcumin's precise mechanisms and function in TBI.

Eleven grand challenges in single-cell data science.

The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands-or even millions-of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.

Tubulin-binding cofactor E-like (TBCEL), the protein product of the mulet gene, is required in the germline for the regulation of inter-flagellar microtubule dynamics during spermatid individualization.

Individual sperm cells are resolved from a syncytium during late step of spermiogenesis known as individualization, which is accomplished by an Individualization Complex (IC) composed of 64 investment cones. mulet encodes Tubulin-binding cofactor E-like (TBCEL), suggesting a role for microtubule dynamics in individualization. Indeed, a population of ∼100 cytoplasmic microtubules fails to disappear in mulet mutant testes during spermatogenesis. This persistence, detected using epi-fluorescence and electron microscopy, suggests that removal of these microtubules by TBCEL is a prerequisite for individualization. Immunofluorescence reveals TBCEL expression in elongated spermatid cysts. In addition, testes from mulet mutant males were rescued to wild type using tubulin-Gal4 to drive TBCEL expression, indicating that the mutant phenotype is caused by the lack of TBCEL. Finally, RNAi driven by bam-GAL4 successfully phenocopied mulet, confirming that mulet is required in the germline for individualization. We propose a model in which the cytoplasmic microtubules serve as alternate tracks for investment cones in mulet mutant testes.This article has an associated First Person interview with the first author of the paper.

DNA sequence representation without degeneracy.

Graphical representation of DNA sequence provides a simple way of viewing, sorting and comparing various gene structures. A new two-dimensional graphical representation method using a two- quadrant Cartesian coordinates system has been derived for mathematical denotation of DNA sequence. The two-dimensional graphic representation resolves sequences' degeneracy and is mathematically proven to eliminate circuit formation. Given x-projection and y-projection of any point on the graphical representation, the number of A, G, C and T from the beginning of the sequence to that point could be found. Compared with previous methods, this graphical representation is more in-line with the conventional recognition of linear sequences by molecular biologists, and also provides a metaphor in two dimensions for local and global DNA sequence comparison.