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Bad Homburg vor der Höhe, Germany

Lang S.,Medical Biochemistry and Molecular Biology | Benedix J.,Medical Biochemistry and Molecular Biology | Fedeles S.V.,Yale University | Schorr S.,Medical Biochemistry and Molecular Biology | And 13 more authors.
Journal of Cell Science | Year: 2012

Co-translational transport of polypeptides into the endoplasmic reticulum (ER) involves the Sec61 channel and additional components such as the ER lumenal Hsp70 BiP and its membrane-resident co-chaperone Sec63p in yeast. We investigated whether silencing the SEC61A1 gene in human cells affects co- and post-translational transport of presecretory proteins into the ER and post-translational membrane integration of tail-anchored proteins. Although silencing the SEC61A1 gene in HeLa cells inhibited co- and post-translational transport of signal-peptide-containing precursor proteins into the ER of semi-permeabilized cells, silencing the SEC61A1 gene did not affect transport of various types of tail-anchored protein. Furthermore, we demonstrated, with a similar knockdown approach, a precursor-specific involvement of mammalian Sec63 in the initial phase of co-translational protein transport into the ER. By contrast, silencing the SEC62 gene inhibited only post-translational transport of a signal-peptide-containing precursor protein. © 2012.

Tordjman S.,University of Rennes 1 | Tordjman S.,CNRS Laboratory of Physiology of Perception | Anderson G.M.,Yale University | Kermarrec S.,University of Rennes 1 | And 14 more authors.
Psychoneuroendocrinology | Year: 2014

Background: Reports of higher stress responsivity, altered sleep-wake cycle and a melatonin deficit in autism have stimulated interest in the cortisol circadian rhythm in individuals with autism. Methods: The study was conducted on 55 low-functioning children and adolescents with autism (11.3. ±. 4.1 years-old) and 32 typically developing controls (11.7. ±. 4.9 years-old) matched for age, sex and puberty. Behavioral assessment was performed using the Autism Diagnostic Observation Schedule (ADOS). Salivary samples for measurement of cortisol were collected during a 24-h period (at least 0800. h-Day1, 1600. h, 0800. h-Day2 for 46 individuals with autism and 27 controls, and 0800. h-Day1, 1100. h, 1600. h, 2400. h, 0800. h-Day2 for 13 individuals with autism and 20 controls). Overnight (2000. h-0800. h) urinary cortisol excretion was also measured. Results: The autism group displayed significantly higher levels of salivary cortisol at all time-points, flatter daytime and nighttime slopes, higher 0800. h cortisol levels on Day2 compared to Day1, and greater variances of salivary and urinary cortisol. There was a significant relationship between salivary cortisol levels and impairments in social interaction and verbal language. Overnight urinary cortisol excretion was similar in the autism and control groups. Conclusion: Anticipation of the stressful collection procedure appears to contribute to the higher 0800. h-Day2 versus 0800. h-Day1 salivary cortisol levels in autism. This sensitization to stressors might be as, or even more, important clinically than exposure to novelty in autism. The similar group means for overnight urinary cortisol excretion indicate that basal HPA axis functioning is unaltered in low-functioning autism. The elevated salivary cortisol levels observed in autism over the 24-h period in a repeated stressful condition, flattened diurnal cortisol patterns and the apparent effect of anticipation are consistent with prior findings in high trait anxiety. © 2014 Elsevier Ltd.

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