No abstract

SignificanceOur coarse-grained molecular dynamics (CGMD) simulations show that the deposition of nanoscale knobs, rather than spectrin network remodeling, is the primary cause of the dramatically increased stiffness of the Plasmodium falciparum (Pf)-infected red blood cell (RBC) membranes. Our analyses further reveal that the knobs stiffen the RBC membrane in a unique manner by simultaneously harnessing composite strengthening, strain hardening, and knob density-dependent vertical coupling effects. In addition to providing a fundamental understanding of the stiffening mechanism of Pf-infected RBCs, our simulation results suggest potential targets for antimalarial therapies.

MicroRNAs (miRNAs) regulate many cellular events during brain development by interacting with hundreds of mRNA transcripts. However, miRNAs operate non-uniformly upon the transcriptional profile with an as yet unknown logic. Shortcomings in defining miRNA-mRNA networks are limited knowledge of in vivo miRNA targets, and their abundance in single cells. By combining multiple complementary approaches, AGO2-HITS-CLIP, single-cell profiling, and innovative computational analyses using bipartite and co-expression networks, we show that miRNA-mRNA interactions operate as functional modules that often correspond to cell-type identities and undergo dynamic transitions during brain development. These networks are highly dynamic during development and over the course of evolution. One such interaction is between radial glia-enriched ORC4 and miR-2115, a great ape specific miRNA, which appears to control radial glia proliferation rates during human brain development.

Cold atmospheric pressure plasmas have proven to provide an alternative treatment of cancer by targeting tumorous cells while leaving their healthy counterparts unharmed. However, the underlying mechanisms of the plasma-cell interactions are not yet fully understood. Reactive oxygen species, and in particular hydroxyl radicals (OH), are known to play a crucial role in plasma driven apoptosis of malignant cells. In this paper we investigate the interaction of OH radicals, as well as H 2 O 2 molecules and HO 2 radicals, with DNA by means of reactive molecular dynamics simulations using the ReaxFF force field. Our results provide atomic-scale insight into the dynamics of oxidative stress on DNA caused by the OH radicals, while H 2 O 2 molecules appear not reactive within the considered timescale. Among the observed processes are the formation of 8-OH-adduct radicals, forming the first stages towards the formation of 8-oxoGua and 8-oxoAde, H-abstraction reactions of the amines, and the partial opening of loose DNA ends in aqueous solution.

We seek to elucidate the role of macromolecular crowding in transcription and translation. It is well known that stochasticity in gene expression can lead to differential gene expression and heterogeneity in a cell population. Recent experimental observations by Tan et al. have improved our understanding of the functional role of macromolecular crowding. It can be inferred from their observations that macromolecular crowding can lead to robustness in gene expression, resulting in a more homogeneous cell population. We introduce a spatial stochastic model to provide insight into this process. Our results show that macromolecular crowding reduces noise (as measured by the kurtosis of the mRNA distribution) in a cell population by limiting the diffusion of transcription factors (i.e. removing the unstable intermediate states), and that crowding by large molecules reduces noise more efficiently than crowding by small molecules. Finally, our simulation results provide evidence that the local variation in chromatin density as well as the total volume exclusion of the chromatin in the nucleus can induce a homogenous cell population.