Fragile X mental retardation is caused by absence of the RNAbinding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1-knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo. This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome.dendrites ͉ metabotropic glutamate receptor ͉ mRNA ͉ plasticity ͉ ultrastructure F ragile X mental retardation syndrome is an inherited, Xlinked disorder. In most patients, methylation of an extreme expansion (200-1,000 repeats) of a (CGG)n trinucleotide repeat in the 5Ј UTR of the FMR1 gene blocks transcription of fmr1 mRNA (1). The resulting absence of fragile X mental retardation protein (FMRP) causes the syndrome, which is characterized by mental retardation, macroorchidism, and behavioral abnormalities (2). The brains of these patients exhibit an unusual, spindly appearance of the dendritic spines as well as an overabundance of spines (3, 4), a morphology that resembles early postnatal tissue.The function of FMRP is unknown; in neurons much of the protein is found in dendrites (5). FMRP contains RNA-binding elements (6) and is associated with actively translating polyribosomes in the brain (7-9). Several laboratories have described sets of mRNAs bound by FMRP (10-12), and specific motifs involved in FMRP binding of some mRNAs have been identified (13,14). Recently, we demonstrated (10) that several members of a subset of mRNAs bound by FMRP in intact cells are differentially distributed and͞or translated in dendritic, as compared to somatic, subcellular domains. This finding suggests direct involvement of FMRP in transport and͞or translation of mRNA in dendrites. Antar et al. (15) have demonstrated rapid transport of FMRP into dendrites upon KCl depolarization. We report here that a dynamic aspect of translation, neurotransmitter-induced rapid initiation, is directly impacted by the absence of FMRP.Protein translation in dendrites was suggested by early descriptions of postsynaptic polyribosomal aggregates (PRAs) during synaptogenesis and in the visual cortex of rats reared in complex environments, indicating the importance of local translation for synaptic plasticity (16,17). Components necessary for translation are present postsynaptic...

An alarmingly high incidence of HCV re-infection was found in this group. This high re-infection rate indicates that current prevention measures should be discussed, frequent HCV RNA testing should be continued after successful treatment and, in case of possible relapse, clade typing should be performed to exclude re-infection.

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics.Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression.Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0–52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63–15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04–12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02–6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27–192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39–8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19–2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60–14.53) had significant effects on HCV acquisition.Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.

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