To die or not to die: death signaling in nonalcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease worldwide. In subset of patients, NAFLD progresses to its advanced form, nonalcoholic steatohepatitis (NASH), which is accompanied with inflammation and fibrosis. Saturated free fatty acid-induced hepatocyte apoptosis is a feature of NASH. Death signaling in NASH does not always result in apoptosis, but can alternatively lead to the survival of cells presenting signs of pro-inflammatory and pro-fibrotic signals. With the current lack of established treatments for NASH, it is important to understand the molecular mechanisms responsible for disease development and progression. This review focuses on the latest findings in hepatocyte death signaling and discusses possible targets for intervention, including caspases, death receptor and c-Jun N-terminal kinase 1 signaling, oxidative stress, and endoplasmic reticulum stress, as well as epigenomic factors.

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Characterization and modelling of looming-sensitive neurons in the crab Neohelice

Abstract

Looming-sensitive neurons (LSNs) are motion-sensitive neurons tuned for detecting imminent collision. Their main characteristic is the selectivity to looming (a 2D representation of an object approach), rather than to receding stimuli. We studied a set of LSNs by performing surface extracellular recordings in the optic nerve of Neohelice granulata crabs, and characterized their response against computer-generated visual stimuli with different combinations of moving edges, highlighting different components of the optical flow. In addition to their selectivity to looming stimuli, we characterized other properties of these neurons, such as low directionality; reduced response to sustained excitement; and an inhibition phenomenon in response to visual stimuli with dense optical flow of expansion, contraction, and translation. To analyze the spatio-temporal processing of these LSNs, we proposed a biologically plausible computational model which was inspired by previous computational models of the locust lobula giant motion detector (LGMD) neuron. The videos seen by the animal during electrophysiological experiments were applied as an input to the model which produced a satisfactory fit to the measured responses, suggesting that the computation performed by LSNs in a decapod crustacean appears to be based on similar physiological processing previously described for the LGMD in insects.

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Examining Mechanisms and Moderators of the Relationship Between Discriminatory Health Care Encounters and Attempted Suicide Among U.S. Transgender Help-Seekers

Abstract

This study examined how experiences of service denial and discrimination in three health care settings—doctors' offices, emergency rooms, and mental health clinics—might contribute to attempted suicide among transgender adults. Mechanisms of this relationship were examined, including treatment receipt and the use of substances to cope with mistreatment. Perceived emotional social support was also tested as a potential protective factor against the deleterious effects of service denial and discrimination on treatment receipt, substance use, and attempted suicide. The analysis included 4190 respondents from the National Transgender Discrimination Survey. Structural equation modeling was employed to test hypothesized relationships. Being denied a greater number of services and discriminated against in more settings were associated with lower levels of treatment receipt. Service denial was also correlated with increased rates of coping-motivated substance use and elevated rates of attempted suicide. Treatment receipt mediated the relationships between service denial/discrimination and substance use. Substance use mediated the relationship between treatment receipt and attempted suicide. Higher levels of support were protective to treatment receipt when denied services in one setting, but no longer retained protective effects when denied in two or three settings. Results have critical implications for service access and delivery and policies that protect transgender help-seekers in the health care system.

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Factors Associated with Assignment of Therapeutic Homework in a Large Public Children’s Mental Health System

Abstract

Therapeutic homework is a fundamental skill-building component of the majority of evidence-based therapies and is associated with better treatment outcomes. However, it is rarely utilized in public mental health settings. To determine barriers to homework use and identify predictors of clinicians' assignment of homework, an online survey was administered to 267 clinicians in a large diverse public mental health system. Clinicians who were younger, licensed, whose supervisors asked about homework and whose clients completed their homework more frequently were predictors of greater homework utilization. The survey results are discussed and a novel idea to increase the use of homework is introduced.

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Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and Exaggerated?

Abstract

Blood pressure responses to graded exercise testing can provide important diagnostic and prognostic information. While published guidelines outline what constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response to exercise testing, the widespread use of exaggerated blood pressure responses as a clinical tool is limited due to sparse and inconsistent data. A review of the original sources from these guidelines reveals an overall lack of empirical evidence to support both the normal blood pressure responses and their upper limits. In this current opinion, we critically evaluate the current exercise blood pressure guidelines including (1) the normal blood pressure responses to graded exercise testing; (2) the upper limits of this normal response; (3) the blood pressure criteria for test termination; and (4) the thresholds for exaggerated blood pressure responses. We provide evidence that exercise blood pressure responses vary according to subject characteristics, and subsequently a re-evaluation of what constitutes normal and abnormal responses is necessary to strengthen the clinical utility of this assessment.

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The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle

Abstract

Purpose

Dietary protein and resistance exercise (RE) are both potent stimuli of the mammalian target of rapamycin complex 1 (mTORC1). Sestrins1, 2, 3 are multifunctional proteins that regulate mTORC1, stimulate autophagy and alleviate oxidative stress. Of this family, Sestrin2 is a putative leucine sensor implicated in mTORC1 and AMP-dependent protein kinase (AMPK) regulation. There is currently no data examining the responsiveness of Sestrin2 to dietary protein ingestion, with or without RE.

Methods

In Study 1, 16 males ingested either 10 or 20 g of milk protein concentrate (MPC) with muscle biopsies collected pre, 90 and 210 min post-beverage consumption. In Study 2, 20 males performed a bout of RE immediately followed by the consumption of 9 g of MPC or carbohydrate placebo. Analysis of Sestrins, AMPK and antioxidant responses was examined.

Results

Dietary protein ingestion did not result in Sestrin2 mobility shift. After RE, Sestrin2 phosphorylation state was significantly altered and was not further modified by post-exercise protein or carbohydrate ingestion. With RE, AMPK phosphorylation remained stable, while the mRNA expressions of several antioxidants were upregulated.

Conclusions

Dietary protein ingestion did not affect the signalling by the family of Sestrins. With RE, Sestrin2 was hyperphosphorylated, with no further evidence of a relationship to AMPK signalling.

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Fidget Spinner Ingestion

No abstract available

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