The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest-specific 5 (Gas5) noncoding RNA, which is abundant in cells whose growth has been arrested due to lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the DNA-binding domain of the glucocorticoid receptor (GR) by acting as a decoy "glucocorticoid response element (GRE)", thus, competing with DNA GREs for binding to the GR. We conclude that Gas5 is a riborepressor of the GR, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the GR.

Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with each other at different signaling levels, and dysregulation of either system may lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.

Glucocorticoids, end products of the hypothalamic-pituitary-adrenal axis, influence functions of virtually all organs and tissues through the glucocorticoid receptor (GR). Circulating levels of glucocorticoids fluctuate naturally in a circadian fashion and regulate the transcriptional activity of GR in target tissues. The basic helix-loop-helix protein CLOCK, a histone acetyltransferase (HAT), and its heterodimer partner BMAL1 are self-oscillating transcription factors that generate circadian rhythms in both the central nervous system and periphery. We found that CLOCK/BMAL1 repressed GR-induced transcriptional activity in a HAT-activity- dependent fashion. In serum-shock-synchronized cells, transactivational activity of GR, accessed by mRNA expression of an endogenous-responsive gene, fluctuated spontaneously in a circadian fashion in reverse phase with CLOCK/BMAL1 mRNA expression. CLOCK and GR interacted with each other physically, and CLOCK suppressed binding of GR to its DNA recognition sequences by acetylating multiple lysine residues located in its hinge region. These findings indicate that CLOCK/BMAL1 functions as a reverse-phase negative regulator of glucocorticoid action in target tissues, possibly by antagonizing biological actions of diurnally fluctuating circulating glucocorticoids. Further, these results suggest that a peripheral target tissue circadian rhythm indirectly influences the functions of every organ and tissue inside the body through modulation of the ubiquitous and diverse actions of glucocorticoids.

Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017). The data provides important information on autonomous vehicles accidents’ dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama.

The addition of dexamethasone to bupivacaine significantly prolonged the duration of the motor block and improved the quality of analgesia following interscalene block. There was no difference in the duration of analgesia and motor block between low-dose and high-dose dexamethasone.

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TNF-alpha is differentially manifested according to the components that make up the aspirate but the levels of TNF-alpha expression do not correlate with the severity of the resultant injury. However, the reduction in acid-induced lung injury by anti-TNF-alpha treatment indicates that TNF-alpha plays a role in the pathogenesis of aspiration pneumonitis.