FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

Inflammatory pseudotumor of the uterus: A case report

We herein report a case of inflammatory pseudotumor of the uterus, which is a very unusual site for the lesion, To the best of our knowledge, only 2 cases of inflammatory pseudotumor of the uterus have been reported

Frontal epidural metastasis of follicular carcinoma

Papillary-follicular thyroid carcinoma usually remains localized to the thyroid bed, and in cases of metastasis, almost always involves the lungs, bones, or liver. Brain metastasis is rare and there has been no reported case of epidural metastasis of thyroid carcinomas in the literature up to date. A frontal epidural mass lesion was excised and histologically found to be a follicular thyroid carcinoma metastasis

Energy and momentum relaxation of hot electrons in GaN/AlGaN

We report the experimental studies of hot-electron energy and momentum relaxation in the steady state in GaN/AlGaN HEMT structures with a high two-dimensional electron density of n = 1.5 x 10(13) cm(-2). From the LO-phonon-scattering-limited component of the mobility we obtain for the LO phonon the energy of homega similar to 90 meV and the momentum relaxation time of tau(m) similar to 4 fs. Drift velocity versus electric field characteristics obtained from the pulsed I-V measurements show that, at T-L = 77 K, the drift velocity saturates at upsilon(d) = 1.0 X 10(7) cm s(-1) at electric fields in excess of E similar to 7.5 kV cm(-1), and at T-L = 300 K it saturates at upsilon(d) similar to 5 x 10(6) cm s(-1), at an electric field of around E similar to 10 kV cm(-1). Electron temperature as a function of applied electric field is obtained by comparing the measured electric field dependence of the mobility mu(E) at a fixed lattice temperature, with the lattice temperature dependence of the mobility at a fixed low electric field. The electron energy loss rate is then determined from the electron temperature dependence of the power loss using the power balance equations. The effect of hot-phonon production on the observed momentum and energy relaxation of hot electrons is discussed within the framework of a theoretical model, which was originally developed for III-V material systems and has been adapted for a two-dimensional electron gas in GaN, and in which phonon drift is neglected

Urinary N-acetyl-beta-D-glucosaminidase activity in rabbits with experimental hypercalciuria

Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-beta-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D-3 was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorus and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8 +/- 1.5 vs. 12.2 +/- 1.3 mg/dl, 4.6 +/- 0.6 vs. 6.7 +/- 0.7 mg/dl, 22.3 +/- 8.3 vs. 46.8 +/- 22.5 mg/kg per day, and 138.0 +/- 57.1 vs. 70.1 +/- 33.1 IU/l, respectively (P 0.05). The relationship between the urinary NAG/ creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P <0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria