Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

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Effects of Arousal on Mouse Sensory Cortex Depend on Modality

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Obesity in Adolescence Predicts Lower Educational Attainment and Income in Adulthood: The Project EAT Longitudinal Study

Objective

Prospective associations between obesity in adolescence and adult socioeconomic outcomes, and potential mediators, were examined in a contemporary cohort.

Methods

Longitudinal data collected in 1998 to 1999 (Project EAT‐I) and 2015 to 2016 (EAT‐IV) were analyzed for 1,796 participants who provided data at both time points. Adolescents (mean age = 14.8 years) self‐reported demographic and psychosocial variables (EAT‐I) and follow‐up outcomes (EAT‐IV). Body weight and height were directly measured. Bachelor's degree or more education, income ≥ US $50,000, and partnered status at follow‐up were examined by baseline obesity (>95th BMI percentile) using logistic regression. Self‐esteem, depression, and weight‐related teasing were examined as mediators using multivariate probit regressions. All analyses were adjusted for race, baseline age, and parent socioeconomic status.

Results

Girls with obesity were significantly less likely to have achieved a bachelor’s degree (OR 0.32, 95% CI [0.18, 0.58]; P < 0.001), earn ≥ $50,000 annually (OR 0.57, 95% CI [0.33, 0.99]; P < 0.04), or be partnered (OR 0.45, 95% CI [0.27, 0.75]; P < 0.002) in adulthood. No associations were observed among boys. Among girls, depression mediated 8.5% and 23.6% of the association between adolescent obesity and adult education and income, respectively.

Conclusions

Adolescent girls with obesity have lower educational attainment and income and are less likely to be partnered in later adulthood. Depression may partly mediate the associations.

     

Combined Human Genome-wide RNAi and Metabolite Analyses Identify IMPDH as a Host-Directed Target against Chlamydia Infection

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PHLDA1 (pleckstrin homology-like domain,family A,member 1) knockdown promotes migration and invasion of MCF10A breast epithelial cells

PHLDA1 (pleckstrin homology-like domain, family A, member 1) is a multifunctional protein that plays distinct roles in several biological processes including cell death and therefore its altered expression has been identified in different types of cancer. Progressively loss of PHLDA1 was found in primary and metastatic melanoma while its overexpression was reported in intestinal and pancreatic tumors. Previous work from our group showed that negative expression of PHLDA1 protein was a strong predictor of poor prognosis for breast cancer disease. However, the function of PHLDA1 in mammary epithelial cells and the tumorigenic process of the breast is unclear. To dissect PHLDA1 role in human breast epithelial cells, we generated a clone of MCF10A cells with stable knockdown of PHLDA1 and performed functional studies. To achieve reduced PHLDA1 expression we used shRNA plasmid transfection and then changes in cell morphology and biological behavior were assessed. We found that PHLDA1 downregulation induced marked morphological alterations in MCF10A cells, such as changes in cell-to-cell adhesion pattern and cytoskeleton reorganization. Regarding cell behavior, MCF10A cells with reduced expression of PHLDA1 showed higher proliferative rate and migration ability in comparison with control cells. We also found that MCF10A cells with PHLDA1 knockdown acquired invasive properties, as evaluated by transwell Matrigel invasion assay and showed enhanced colony-forming ability and irregular growth in low attachment condition. Altogether, our results indicate that PHLDA1 downregulation in MCF10A cells leads to morphological changes and a more aggressive behavior.     

Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.     

Examining the sources of variability in cell culture media used for biopharmaceutical production

Raw materials, in particular cell culture media, represent a significant source of variability to biopharmaceutical manufacturing processes that can detrimentally affect cellular growth, viability and specific productivity or alter the quality profile of the expressed therapeutic protein. The continual expansion of the biopharmaceutical industry is creating an increasing demand on the production and supply chain consistency for cell culture media, especially as companies embrace intensive continuous processing. Here, we provide a historical perspective regarding the transition from serum containing to serum-free media, the development of chemically-defined cell culture media for biopharmaceutical production using industrial scale bioprocesses and review production mechanisms for liquid and powder culture media. An overview and critique of analytical approaches used for the characterisation of cell culture media and the identification of root causes of variability are also provided, including in-depth liquid phase separations, mass spectrometry and spectroscopic methods.     

Behavioral and Biochemical Effects of N-Acetylcysteine in Zebrafish Acutely Exposed to Ethanol

Neurochemical Research - Alcohol hangover refers to unpleasant symptoms experienced as a direct consequence of a binge drinking episode. The effects observed in this condition are related to the...