Peer-mediated social intervention for young children with autism

In this paper, we trace the history of peer-mediated intervention for young children with autism. Special attention is paid to outcomes achieved, implementation strategies, practicality, combining peer-mediation and naturalistic teaching, and overall conclusions from 20 years of study.     

Increase in brain stem cytokine mRNA levels as an early response to chemical-induced myelin edema

This study examined the early response of pro-inflammatory and regulatory cytokines in the mouse brain following triethyltin (TET)-induced myelin injury characterized by edematous vacuolation. Following an acute intraperitoneal injection of triethyltin (TET) sulfate (3 mg/kg) to 17-day old CD1 mice, significant increases in brain stem TNF-alpha and IL-1alpha mRNA levels occurred at 6 and 24 h, respectively with elevations in TGF-beta1 and MIP-1alpha at 1 h. In the cortex, responses were limited to elevations at 6 h in TNF-alpha, TGF-beta1 and MIP-1alpha. These data suggest that a chemokine/cytokine response can occur with minimal alterations to the integrity of the myelin sheath and may contribute to the initial signaling mechanisms associated with demyelinating disorders.     

Vav regulates peptide-specific apoptosis in thymocytes

Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns.     

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 3. Structure-activity relationship and optimization of the N-aryl substituent

3-?4-[2-(Benzoxazol-2-ylmethylamino)ethoxy]phenyl?-(2S)-((2- benzoylph enyl)amino)propionic acid (1) and (2S)-((2-benzoylphenyl)amino)-3-?4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl?propionic acid (2) are peroxisome proliferator-activated receptor gamma (PPARgamma) agonists and have antidiabetic activity in rodent models of type 2 diabetes. As part of an effort to develop the SAR of the N-2-benzoylphenyl moiety of 1 and 2, a series of novel carboxylic acid analogues, 23-66, modified only in the N-2-benzoylphenyl moiety were synthesized from L-tyrosine and evaluated as PPARgamma agonists. In general, only modest changes in the N-2-benzoylphenyl moiety of 1 and 2 are tolerated. More specifically, the best changes involve bioisosteric replacement of one of the two phenyl rings of this moiety. Addition of substituents to this moiety generally produced compounds that are less active in the cell-based functional assays of PPARgamma activity although binding affinity to PPARgamma may be maintained. A particularly promising set of analogues is the anthranilic acid esters 63-66 in which the phenyl ring in the 2-benzoyl group of 1 and 2 has been replaced by an alkoxy group. In particular, (S)-2-(1-carboxy-2-?4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phen yl? ethylamino)benzoic acid methyl ester (63) has a pKi of 8.43 in the binding assay using human PPARgamma ligand binding domain and a pEC50 of 9.21 in the in vitro murine lipogenesis functional assay of PPARgamma activity. Finally, 63 was found to normalize glycemia when dosed at 3 mg/kg bid po in the Zucker diabetic fatty rat model of type 2 diabetes.     

Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve

The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T2 values approximately 30-50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T2 component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T2 measurements to measure the degree of myelination. The signal contribution of each T2 component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.