Upon weaning, we subjected mice from each strain to either an iron-deficient or iron-adequate diet. After 100 days of dietary treatment, we measured the effects of ID on gene expression in the ventral midbrain, a region containing the substantia nigra. The substantia nigra is the base of the nigrostriatal dopamine pathway and a region particularly affected by iron loss in RLS. We screened for ID-induced changes in expression, including changes in that of both iron-regulating and dopamine-related genes. Results revealed a number of expression changes occurring in ID, with large strain-dependent differences in the genes involved and number of expression
changes occurring. In terms of dopamine-related genes, results revealed ID-induced expression changes in three genes with direct ties to nigrostriatal dopamine functioning, two of which have never before been implicated find more in an iron dopamine pathway. These were stromal cell-derived factor 1 (Cxcl12, or SDF-1), a ferritin regulator and BIBF 1120 potent dopamine neuromodulator, and hemoglobin, beta adult chain 1 (Hbb-b1), a gene recently shown to play a functional
role in dopaminergic neurons. The extent of up-regulation of these genes varied by strain. This work not only demonstrates a wide genetic variation in the transcriptional response to ID in the brain, but also reveals two novel biochemical pathways by which
iron may potentially alter dopamine function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Tailed phages are genome delivery machines exhibiting unequaled efficiency acquired over more than 3 billion years of evolution. Siphophages from the P335 and 936 families infect the Gram-positive bacterium Lactococcus lactis using receptor-binding proteins anchored to the host adsorption apparatus (baseplate). Crystallographic PX-478 clinical trial and electron microscopy (EM) studies have shed light on the distinct adsorption strategies used by phages of these two families, suggesting that they might also rely on different infection mechanisms. Here, we report electron microscopy reconstructions of the whole phage TP901-1 (P335 species) and propose a composite EM model of this gigantic molecular machine. Our results suggest conservation of structural proteins among tailed phages and add to the growing body of evidence pointing to a common evolutionary origin for these virions. Finally, we propose that host adsorption apparatus architectures have evolved in correlation with the nature of the receptors used during infection.”
“Obsessive-compulsive disorder (OCD) is a common psychiatric disorder characterized by the occurrence of obsessions and compulsions. Glutamatergic abnormalities have been related to the pathophysiology of OCD.