Patterns of gene expression in the frontal cortex discriminate alcoholic from non-alcoholic individuals

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (similar to 47 000 elements) was performed on the superior frontal cortex of 27 individual human cases ( 14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

A need for caution in the use of frontal analysis continuous capillary electrophoresis for the determination of ligand binding data

Attention is drawn to a need for caution in the determination of binding data for protein-polyelectrolyte interactions by frontal analysis continuous capillary electrophoresis (FACCE). Because the method is valid only for systems involving comigration of complex(es) and slower-migrating reactant, establishing conformity with that condition is clearly a prerequisite for its application. However, that requirement has not been tested in any published studies thus far. On the basis of calculated FACCE patterns, presented to illustrate features by which such comigration of complex(es) and slower-migrating reactant can be identified, the form of the published pattern for a P-lactoglobulin-poly(styrenesulfonate) mixture does not seem to signify the migration behavior required to justify its consideration in such terms. Additional experimental studies are therefore needed to ascertain the validity of FACCE as a means of determining binding data for the characterization of protein-polyelectrolyte interactions. (c) 2005 Elsevier Inc. All rights reserved.

Segmental lung lobe torsion in a 7-week-old Pug

Case summary: A 7-week-old, intact female Pug was referred with an acute history of expiratory dyspnea, tachypnea, and pyrexia. Radiologic evaluation revealed bilateral pleural effusion and a poorly demarcated area of soft tissue opacity cranial to the heart. The presence of air bronchograms in the cranial lung lobes suggested alveolar parenchymal pathology consistent with pulmonary edema, congestion, or cellular infiltration. Exploratory thoracotomy revealed a segmental torsion of the left cranial lung lobe. The affected lobe was removed and the puppy recovered uneventfully. Unique information: Lung lobe torsion tends to occur more frequently in mature large breed dogs at a mean age of 3 years. The age, breed, and segmental nature of the torsion in the reported case are contrary to most of the previously documented cases of lung lobe torsion. To the authors' knowledge, this is the first report of lung lobe torsion in a 7-week-old dog.

Gene expression in human alcoholism: Microarray analysis of frontal cortex

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were downregulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.

Upregulation of beta catenin in superior frontal cortex of chronic alcoholics

Chronic alcohol abuse causes neurotoxicity and the development of tolerance and dependence. At the molecular level, however, knowledge about mechanisms underlying alcoholism remains limited. In this study we examined the superior frontal cortex, one of the most vulnerable brain regions, of alcoholics and of age- and gender-matched control subjects by means of antibody microarrays and Western blot analyses, and identified an up-regulation of beta-catenin level in the superior frontal cortex of alcoholics. Beta-catenin is the orthologue of the Drosophila armadillo segment polarity gene and a down stream component of the Wnt and Akt signaling pathway. Beta-catenin was identified as a cell adhesion molecule of the cadherin family which binds to the actin cytoskeleton. Genetic and biochemical analyses also found that beta-catenin can be translocated from the cytoplasm to the nucleus and acts as a transcription factor. In addition, electron microscopy performed on rat brain tissue sections has localized the beta-catenin and cadherin complexes to the synapses where they border the active zone. Because of the multi-functional role of beta-catenin in the nervous system, this study provides the premise for further investigation of mechanisms underlying the up-regulation of beta-catenin in alcoholism, which may have considerable pathogenic and therapeutic relevance.

Upregulation of beta-catenin protein in superior frontal cortex of chronic alcoholics

Chronic alcohol abuse causes neurotoxicity and the development of tolerance and dependence. At the molecular level, however, knowledge of underlying mechanisms remains limited. In this study we examined the superior frontal cortex, an area vulnerable to neuronal loss, of alcoholics and age- and gender-matched control subjects by means of antibody arrays and Western blot analyses, and found an upregulation of b-catenin protein in the alcoholics.

Avaliação da influência dos formatos DICOM e JPEG na reprodutibilidade de pontos cefalométricos em Telerradiografia digital em Norma Frontal

A imagem digital no formato DICOM requer grande espaço para armazenamento, dificultando o arquivamento e transmissão da imagem via internet, sendo necessária, muitas vezes, a compressão das imagens por meio de formatos de arquivo como o JPEG. O objetivo neste estudo foi avaliar a influência dos formatos DICOM e JPEG, nos Fatores de Qualidade 100, 80 e 60, na reprodutibilidade intra e interexaminador na marcação de pontos cefalométricos em Telerradiografias digitais em Norma Frontal. A amostra consistiu de 120 imagens digitais de Telerradiografias em Norma Frontal, obtidas de 30 indivíduos. As 30 imagens originais, em formato DICOM, posteriormente, foram convertidas para o formato JPEG, nos Fatores de Qualidade 100, 80 e 60. Após cegar e randomizar a amostra, três ortodontistas calibrados marcaram os 18 pontos cefalométricos em cada imagem utilizando um programa de cefalometria computadorizada, que registra as medidas dos pontos cefalométricos em um sistema de coordenadas cartesianas X e Y. Nos resultados, os testes estatísticos de correlações intraclasses e análise de variância (ANOVA) apresentaram concordância de reprodutibilidade dos pontos cefalométricos em Telerradiografias digitais em Norma Frontal, tanto intra como interexaminador, com exceção dos pontos ZL, ZR, AZ, JR, NC, CN na coordenada Y e A6 na coordenada X, independentemente dos formatos de arquivo. Em conclusão, os formatos de arquivo DICOM e JPEG, nos Fatores de Qualidade 100, 80 e 60, não afetaram a reprodutibilidade intra e interexaminador na marcação dos pontos cefalométricos.(AU)

Quantitative differences in beta/A4 protein subtypes in the parahippocampal gyrus and frontal cortex in Alzheimer's disease

The density of diffuse, primitive and classic beta/A4 protein deposits was estimated in sulci and gyri in the frontal cortex and parahippocampal gyrus (PHG) in 8 cases of Alzheimer's disease. Total beta/A4 deposit density was similar in the frontal cortex and PHG but the ratio of primitive and classic deposits to the total was greater in the PHG compared with the frontal cortex. Total beta/A4 deposit density was greater in the depths of the sulci, but the proportions of the various beta/A4 subtypes were similar in sulci and gyri. Hence, increased density of primitive and classic deposits in the PHG could reflect enhanced conversion of diffuse to mature deposits whereas increased density of mature beta/A4 subtypes in sulci versus gyri may reflect increased beta/A4 deposition in the sulci.

Modelling frontal discontinuities in wind fields

A Bayesian procedure for the retrieval of wind vectors over the ocean using satellite borne scatterometers requires realistic prior near-surface wind field models over the oceans. We have implemented carefully chosen vector Gaussian Process models; however in some cases these models are too smooth to reproduce real atmospheric features, such as fronts. At the scale of the scatterometer observations, fronts appear as discontinuities in wind direction. Due to the nature of the retrieval problem a simple discontinuity model is not feasible, and hence we have developed a constrained discontinuity vector Gaussian Process model which ensures realistic fronts. We describe the generative model and show how to compute the data likelihood given the model. We show the results of inference using the model with Markov Chain Monte Carlo methods on both synthetic and real data.

Laminar distribution of the pathological changes in frontal and temporal cortex in 8 patients with progressive supranuclear palsy

OBJECTIVE: To determine the laminar distribution of the pathological changes in the cerebral cortex in progressive supranuclear palsy (PSP). METHOD: The distribution of the abnormally enlarged neurons (EN), surviving neurons, neurofibrillary tangles (NFT), glial inclusions (GI), tufted astrocytes (TA), and neuritic plaques (NP) were studied across the cortex in tau immunolabeled sections of frontal and temporal cortex in 8 cases of PSP. RESULTS: The distribution of the NFT was highly variable with no consistent pattern of laminar distribution. The GI were distributed either in the lower laminae or uniformly across the cortex. Surviving neurons exhibited either a density peak in the upper laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. The EN and glial cell nuclei were distributed primarily in the lower cortical laminae. There were positive correlations between the densities of the EN and glial cell nuclei and negative correlations between the surviving neurons and glial cells. No correlations were present between the densities of the NFT and GI. CONCLUSION: Cortical pathology in PSP predominantly affects the lower laminae but may spread to affect the upper laminae in some cases. The NFT and GI may have different laminar distributions and gliosis occurs concurrently with neuronal enlargement.