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Molecular Correlates (molecular + correlate)

Distribution by Scientific Domains

Medical Sciences	57%
Life Sciences	42%

Selected Abstracts

Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
M. Mengel
In the Banff consensus, infiltrates in areas of scarring are ignored. This study aimed to characterize the molecular correlates and clinical significance of scarring and inflammation in scarred areas. We assessed the extent of interstitial infiltrates, tubulitis and scarring in 129 clinically indicated renal allograft biopsies, and correlated the results with microarray expression data and allograft survival. Findings were validated in 50 additional biopsies. Transplants with scarring had a worse prognosis if the scarred area showed infiltrates. Infiltration in unscarred and scarred areas was associated with reduced death censored graft survival. In microarray analysis, infiltration in unscarred areas strongly (>r ± 0.4) correlated with 484 transcripts associated with cytotoxic T cells, interferon-gamma, macrophages and injury. Scarring correlated with a distinct set of 172 transcripts associated with B cells, plasma cells, and others of unknown significance. The strongest correlation was with four mast cell transcripts. In biopsies with scarring, high expression of mast cell transcripts was associated with reduced graft survival and poor functional recovery. In renal allograft biopsies, infiltrates in scarred areas have implications for poor outcomes. Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes. [source]

A molecular correlate of clinicopathology in transthyretin amyloidosis,

THE JOURNAL OF PATHOLOGY, Issue 1 2009
Mark B Pepys
Abstract The mechanisms responsible for amyloid deposition at different times and in different organs, even in individuals with the same amyloidogenic mutation, are not known. The demonstration, in hereditary systemic transthyretin Val30Met amyloidosis, that such differences are consistently associated with amyloid fibrils composed of different length transthyretin fragments sheds new light on this question and will open the way to further informative studies. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Human solute carrier SLC6A14 is the ,-alanine carrier

THE JOURNAL OF PHYSIOLOGY, Issue 17 2008
Catriona M. H. Anderson
The ,-alanine carrier was characterized functionally in the 1960s to 1980s at the luminal surface of the ileal mucosal wall and is a Na+ - and Cl, -dependent transporter of a number of essential and non-essential cationic and dipolar amino acids including lysine, arginine and leucine. ,-Alanine carrier-like function has not been demonstrated by any solute carrier transport system identified at the molecular level. A series of experiments were designed to determine whether solute carrier SLC6A14 is the molecular correlate of the intestinal ,-alanine carrier, perhaps the last of the classical intestinal amino acid transport systems to be identified at the molecular level. Following expression of the human SLC6A14 transporter in Xenopus laevis oocytes, the key functional characteristics of the ,-alanine carrier, identified previously in situ in ileum, were demonstrated for the first time. The transport system is both Na+ and Cl, dependent, can transport non-,-amino acids such as ,-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. N -methylation of its substrates reduces the affinity for transport. These observations confirm the hypothesis that the SLC6A14 gene encodes the transport protein known as the ,-alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs in the distal regions of the human gastrointestinal tract. [source]

Glucose-induced inhibition: how many ionic mechanisms?

ACTA PHYSIOLOGICA, Issue 3 2010
D. Burdakov
Abstract Sensing of sugar by specialized ,glucose-inhibited' cells helps organisms to counteract swings in their internal energy levels. Evidence from several cell types in both vertebrates and invertebrates suggests that this process involves sugar-induced stimulation of plasma membrane K+ currents. However, the molecular composition and the mechanism of activation of the underlying channel(s) remain controversial. In mouse hypothalamic neurones and neurosecretory cells of the crab Cancer borealis, glucose stimulates K+ currents displaying leak-like properties. Yet knockout of some of the candidate ,leak' channel subunits encoded by the KCNK gene family so far failed to abolish glucose inhibition of hypothalamic cells. Moreover, in other tissues, such as the carotid body, glucose-stimulated K+ channels appear to be not leak-like but voltage-gated, suggesting that glucose-induced inhibition may engage multiple types of K+ channels. Other mechanisms of glucose-induced inhibition, such as hyperpolarization mediated by opening of Cl, channels and depolarization block caused by closure of KATP channels have also been proposed. Here we review known ionic and pharmacological features of glucose-induced inhibition in different cell types, which may help to identify its molecular correlates. [source]

An integrated map of the murine hippocampal proteome based upon five mouse strains

ELECTROPHORESIS, Issue 13 2006
Daniela D. Pollak
Abstract With the advent of proteomics technologies it is possible to simultaneously demonstrate the expression of hundreds of proteins. The information offered by proteomics provides context-based understanding of cellular protein networks and has been proven to be a valuable approach in neuroscience studies. The mouse hippocampus has been a major target of analysis in the search for molecular correlates to neuronal information storage. Although human and rat hippocampal samples have been successfully subjected to proteomic profiling, no elaborate analysis providing the fundamental experimental basis for protein-expression studies in the mouse hippocampus has been carried out as yet. This led us to construct a master map generated from the individual hippocampal proteomes of five different mouse strains. A proteomic approach, based upon 2-DE coupled to MS (MALDI-TOF/TOF) has been chosen in an attempt to establish a comprehensive reference database of proteins expressed in the mouse hippocampus. 469 individual proteins, represented by 1156 spots displaying various functional states of the respective gene products were identified. Proteomic profiling of the hippocampus, a brain region with a pivotal role for neuronal information processing and storage may provide insight into the characteristics of proteins serving this highly sophisticated function. [source]

Wide expressivity variation and high but no gender-related penetrance in two dopa-responsive dystonia families with a novel GCH-I mutation

MOVEMENT DISORDERS, Issue 10 2004
Antonino Uncini MD
Abstract We describe the clinical and molecular correlates in two Italian families with dopa-responsive dystonia (DRD) and the same novel mutation of GTP-cyclohydrolase I (GCH-I) gene. Thirty-five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is present in 7 subjects currently under the age of 40. In 1 patient bilateral foot dystonia was evident at birth suggesting that dystonia may be active as early as in utero. In another patient, dystonia spontaneously remitted in adolescence, to relapse 8 years later, as writer's cramp. Dystonia and parkinsonian signs are present in 5 other patients. In 2 subjects an isolated parkinsonism started over the age of 45. A 5-base pair insertion at codon 242 within exon 6 of GTP-cyclohydrolase I (GCH-I) gene that shifts the reading frame and results in a premature stop at codon 247 with truncation of the polypeptide has been detected in 21 subjects. Considering dystonia and parkinsonism the overall penetrance is 0.71 and not significantly different in men (0.69) and women (0.75). Genealogical studies seem to exclude that these families are related but haplotype analysis suggests a single founder. Our findings in subjects with the same mutation indicate a wide intrafamilial variation in expressivity and high penetrance in DRD but do not confirm the reported influence of gender on GCH-I gene mutation penetrance. © 2004 Movement Disorder Society [source]