Inhibition of 3,4-dihydroxy-l-phenylalanine decarboxylase in rat striatal synaptosomes by amino acids interacting with substrate transport

Dopamine synthesis from 3,4-dihydroxy-l-phenylalanine in rat striatal synaptosomes was inhibited by a number of amino acids with aromatic or large aliphatic side chains. Inhibition was not seen when aromatic amino acid decarboxylase activity was measured in disrupted synaptosomes. Similarly, inhibition of dopamine synthesis from tyrosine was seen in the presence of leucine. The inhibition most likely results from interactions of the amino acids with substrate transport across the synaptosome plasma membrane, rather than directly with the catalytic enzymes. The kinetic data obtained are used to infer information about the relevant transport process; they suggest the potential importance of amino acid efflux as a regulatory step.     

Biallelic genome modification in F0 Xenopus tropicalis embryos using the CRISPR/Cas system

Gene inactivation is an important tool for correlation of phenotypic and genomic data, allowing researchers to infer normal gene function based on the phenotype when the gene is impaired. New and better approaches are needed to overcome the shortfalls of existing methods for any significant acceleration of scientific progress. We have adapted the CRISPR/Cas system for use in Xenopus tropicalis and report on the efficient creation of mutations in the gene encoding the enzyme tyrosinase, which is responsible for oculocutaneous albinism. Biallelic mutation of this gene was detected in the F₀ generation, suggesting targeting efficiencies similar to that of TALENs. We also find that off‐target mutagenesis seems to be negligible, and therefore, CRISPR/Cas may be a useful system for creating genome modifications in this important model organism. genesis 51:827–834. © 2013 Wiley Periodicals, Inc.     

Profilin 1: Do we have a novel proteome‐found biomarker predicting response to anticancer therapy?

About three decades ago, profilin 1 was described as a 15 kDa small protein. It was later shown that profilin 1 is a tumor suppressor in human carcinomas. Recent proteome‐based data additionally demonstrated that the levels of profilin 1 expression could help to predict malignant tumor aggressiveness, response to anticancer therapy and risk of recurrence development.     

Separate and overlapping relationships of inattention and hyperactivity/impulsivity in children and adolescents with attention-deficit/hyperactivity disorder

There is debate regarding the dimensional versus categorical nature of attention-deficit/hyperactivity disorder (ADHD). This study utilized confirmatory factor analysis to examine this issue. ADHD symptoms rated on interviews and rating scales from a large sample of individuals (ages 3–17, 74 % male, 75 % Caucasian) with ADHD were examined (n = 242). Four potential factor structures were tested to replicate prior findings in a sample with a wide age range and included only participants who met DSM-IV-TR diagnostic criteria for ADHD. Correlations with executive function measures were performed to further assess the separability and validity of the derived factors. The data support a bifactor model with a general ADHD factor and two specific factors, inattention and hyperactivity/impulsivity. Importantly, the individual factors were also differentially correlated with executive functioning measures. This study adds to a growing literature suggesting both a general component to ADHD, as well as dimensional traits of inattention and hyperactivity/impulsivity, associated with distinct executive functioning profiles. The presence of a general underlying factor contraindicates separating the inattentive and combined subtypes of ADHD into distinct disorders.     

Mutant p53 Attenuates the Anti-Tumorigenic Activity of Fibroblasts-Secreted Interferon Beta

Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables individual monitoring of the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment.