Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

Retinoic acid, an active metabolite of dietary vitamin A, acts as a ligand for nuclear receptor transcription factors with more than 500 known target genes. It is becoming increasingly clear that alcohol has a significant impact on cellular retinoic acid metabolism, with resultant effects on its function. Here, we test the hypothesis that chronic alcohol consumption impairs retinoic acid signaling in brown adipose tissue (BAT), leading to impaired BAT function and thermoregulation. All studies were conducted in age-matched, male mice consuming alcohol-containing liquid diets. Alcohol’s effect on BAT was assessed by histology, qPCR, HPLC, LC/MS and measures of core body temperature. Our data show that chronic alcohol consumption decreases BAT mass, with a resultant effect on thermoregulation. Follow-up mechanistic studies reveal a decreased triglyceride content in BAT, as well as impaired retinoic acid homeostasis, associated with decreased BAT levels of retinoic acid in alcohol-consuming mice. Our work highlights a hitherto uncharacterized effect of alcohol on BAT function, with possible implications for thermoregulation and energy metabolism in drinkers. Our data indicate that alcohol’s effects on brown adipose tissue may be mediated through altered retinoic acid signaling

The link between job satisfaction and organizational commitment:differences between public and private sector employees

Employees in the public and private sectors experience different working conditions and employment relationships. Therefore, it can be assumed that their attitudes toward their job and organizations, and relationships between them, are different. The existing literature has identified the relationship between organizational commitment and job satisfaction as interesting in this context. The present field study examines the satisfaction–commitment link with respect to differences between private and public sector employees. A sample of 617 Greek employees (257 from the private sector and 360 from the public sector) completed standardized questionnaires. Results confirmed the hypothesized relationship differences: Extrinsic satisfaction and intrinsic satisfaction are more strongly related to affective commitment and normative commitment for public sector employees than for private sector ones. The results are discussed, limitations are considered, and directions for future research are proposed

Relationship Between the King-Devick Test and Commonly Used Concussion Tests at Baseline

Context: Comprehensive assessments are recommended to evaluate sport-related concussion (SRC). The degree to which the King-Devick (KD) test adds novel information to an SRC evaluation is unknown. Objective: To describe relationships at baseline among the KD and other SRC assessments and explore whether the KD provides unique information to a multimodal baseline concussion assessment. Design: Cross-sectional study. Setting: Five National Collegiate Athletic Association institutions participating in the Concussion Assessment, Research and Education (CARE) Consortium. Patients or other participants: National Collegiate Athletic Association student-athletes (N = 2258, age = 20 ± 1.5 years, 53.0% male, 68.9% white) in 11 men's and 13 women's sports. Main outcome measure(s): Participants completed baseline assessments on the KD and (1) the Symptom Inventory of the Sport Concussion Assessment Tool-3rd edition, (2) the Brief Symptom Inventory-18, (3) the Balance Error Scoring System, (4) the Standardized Assessment of Concussion (SAC), (5) the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test battery, and (6) the Vestibular/Ocular Motor Screening tool during their first year in CARE. Correlation coefficients between the KD and the 6 other concussion assessments in isolation were determined. Assessments with ρ magnitude >0.1 were included in a multivariate linear regression analysis to evaluate their relative association with the KD. Results: Scores for SAC concentration, ImPACT visual motor speed, and ImPACT reaction time were correlated with the KD (ρ = -0.216, -0.276, and 0.164, respectively) and were thus included in the regression model, which explained 16.8% of the variance in baseline KD time (P < .001, Cohen f2 = 0.20). Better SAC concentration score (β = -.174, P < .001), ImPACT visual motor speed (β = -.205, P < .001), and ImPACT reaction time (β = .056, P = .020) were associated with faster baseline KD performance, but the effect sizes were small. Conclusions: Better performance on cognitive measures involving concentration, visual motor speed, and reaction time was weakly associated with better baseline KD performance. Symptoms, psychological distress, balance, and vestibular-oculomotor provocation were unrelated to KD performance at baseline. The findings indicate limited overlap at baseline among the CARE SRC assessments and the KD

Distinct Populations of Hepatic Stellate Cells in the Mouse Liver Have Different Capacities for Retinoid and Lipid Storage

Hepatic stellate cell (HSC) lipid droplets are specialized organelles for the storage of retinoid, accounting for 50–60% of all retinoid present in the body. When HSCs activate, retinyl ester levels progressively decrease and the lipid droplets are lost. The objective of this study was to determine if the HSC population in a healthy, uninjured liver demonstrates heterogeneity in its capacity for retinoid and lipid storage in lipid droplets. To this end, we utilized two methods of HSC isolation, which leverage distinct properties of these cells, including their vitamin A content and collagen expression. HSCs were isolated either from wild type (WT) mice in the C57BL/6 genetic background by flotation in a Nycodenz density gradient, followed by fluorescence activated cell sorting (FACS) based on vitamin A autofluorescence, or from collagen-green fluorescent protein (GFP) mice by FACS based on GFP expression from a GFP transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i) increased expression of typical markers of HSC activation; (ii) decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT); (iii) decreased triglyceride levels; (iv) increased expression of genes associated with lipid catabolism; and (v) an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1. Conclusion: Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be “primed” and ready for rapid response to acute liver injury

Characterization of 4-HNE Modified L-FABP Reveals Alterations in Structural and Functional Dynamics

4-Hydroxynonenal (4-HNE) is a reactive α,β-unsaturated aldehyde produced during oxidative stress and subsequent lipid peroxidation of polyunsaturated fatty acids. The reactivity of 4-HNE towards DNA and nucleophilic amino acids has been well established. In this report, using proteomic approaches, liver fatty acid-binding protein (L-FABP) is identified as a target for modification by 4-HNE. This lipid binding protein mediates the uptake and trafficking of hydrophobic ligands throughout cellular compartments. Ethanol caused a significant decrease in L-FABP protein (P<0.001) and mRNA (P<0.05), as well as increased poly-ubiquitinated L-FABP (P<0.001). Sites of 4-HNE adduction on mouse recombinant L-FABP were mapped using MALDI-TOF/TOF mass spectrometry on apo (Lys57 and Cys69) and holo (Lys6, Lys31, His43, Lys46, Lys57 and Cys69) L-FABP. The impact of 4-HNE adduction was found to occur in a concentration-dependent manner; affinity for the fluorescent ligand, anilinonaphthalene-8-sulfonic acid, was reduced from 0.347 µM to Kd1 = 0.395 µM and Kd2 = 34.20 µM. Saturation analyses revealed that capacity for ligand is reduced by approximately 50% when adducted by 4-HNE. Thermal stability curves of apo L-FABP was also found to be significantly affected by 4-HNE adduction (ΔTm = 5.44°C, P<0.01). Computational-based molecular modeling simulations of adducted protein revealed minor conformational changes in global protein structure of apo and holo L-FABP while more apparent differences were observed within the internal binding pocket, revealing reduced area and structural integrity. New solvent accessible portals on the periphery of the protein were observed following 4-HNE modification in both the apo and holo state, suggesting an adaptive response to carbonylation. The results from this study detail the dynamic process associated with L-FABP modification by 4-HNE and provide insight as to how alterations in structural integrity and ligand binding may a contributing factor in the pathogenesis of ALD

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols