Transcriptome Kinetics Is Governed by a Genome-Wide Coupling of mRNA Production and Degradation: A Role for RNA Pol II

Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes

On the Complexity of Verifying Concurrent Transition Systems

. In implementation verification, we check that an implementation is correct with respect to a specification by checkingwhether the behaviors of a transition system that models the program's implementation correlate with the behaviors of a transition system that models its specification. In this paper, we investigate the effect of concurrency on the complexity of implementation verification. We consider trace-based and tree-based approaches to the verification of concurrent transition systems, with and without fairness. Our results show that in almost all cases the complexity of the problem is exponentially harder than that of the sequential case. Thus, as in the model-checking verification methodology, the stateexplosion problem cannot be avoided. 1 Introduction While program verification has always been desirable but never easy, the advent of concurrent programming has made it significantly more necessary and difficult. We distinguish between two main methodologies for formal verifi..

Patterns of Active Travel and Physical Activity among Adolescents in Israel

Active travel (AT) is a core physical activity (PA) indicator for children and youth; contributing to health and wellbeing, at both the individual and societal levels. This analysis explores patterns of adolescent active school travel (AST) and cycling and associations with different PA measures. Secondary analysis of the cross-sectional 2018–2019 Health Behaviour in School Age Children study in Israel included an extended PA module with walking, cycling and e-cycling modes. The nationally representative sample includes students in grades 6–12 (n = 4407). Analysis of weighted data included descriptive analyses, inferential statistics, and regression analyses. AST was reported by 61.9% of adolescents; 39.3% reported 20 min or more daily AST; 27.1% reported habitual cycling (HC) and 17.4% reported habitual e-cycling (HEC). There are mixed results for socio-economic status and environment. AST and HC were associated with less sedentary hours daily (odds ratio [OR] = 1.190 and 1.397, respectively); HC was associated with positive sports self-rating (OR = 2.394). Stepwise regression analysis found that lower AST duration, time in minutes, was associated with watching television with the family. Promotion of adolescent AT may be associated with increased PA and joint parent-adolescent AT, and was utilized across different socio-demographic groups in Israel

Thermal manipulations in late-term chick embryos have immediate and longer term effects on myoblast proliferation and skeletal muscle hypertrophy

We investigated the cellular and molecular bases for the promotion of muscle development and growth by temperature manipulations (TMs) during late-term chick embryogenesis. We show that incubation at 39.5°C (increase of 1.7°C from normal conditions) from embryonic days 16 to 18 (E16 to E18) for 3 or 6 h daily increased diameter of myofibers as of day 13 of age and enhanced absolute muscle growth relative to controls, until day 35 of age. TMs had immediate (E17) and later (up to 2 wk posthatch) effects in elevating muscle cell proliferation relative to controls. This was indicated by higher DNA incorporation of thymidine and a higher number of cells expressing PCNA in intact muscle, accompanied by higher Pax7 levels, all reflecting a higher number of myogenic cells, and suggesting that the increased hypertrophy can be attributed to a higher reservoir of myogenic progeny cells produced in response to the TM. IGF-I levels were higher in the TM groups than in controls, implying a mechanism by which heat manipulations in chicks affect muscle development, with locally secreted IGF-I playing a major role. Whereas hypertrophy was similar in both TM groups, cell proliferation and Pax7 levels were more robust in the 6-h muscle, mainly posthatch, suggesting a differential effect of various TM periods on cell reservoir vs. hypertrophy and a high sensitivity of myoblasts to relatively small changes in heat duration with respect to these processes, which is manifested in the short and long term