Gene-Expression Signatures Can Distinguish Gastric Cancer Grades and Stages

Microarray gene-expression data of 54 paired gastric cancer and adjacent noncancerous gastric tissues were analyzed, with the aim to establish gene signatures for cancer grades (well-, moderately-, poorly- or un-differentiated) and stages (I, II, III and IV), which have been determined by pathologists. Our statistical analysis led to the identification of a number of gene combinations whose expression patterns serve well as signatures of different grades and different stages of gastric cancer. A 19-gene signature was found to have discerning power between high- and low-grade gastric cancers in general, with overall classification accuracy at 79.6%. An expanded 198-gene panel allows the stratification of cancers into four grades and control, giving rise to an overall classification agreement of 74.2% between each grade designated by the pathologists and our prediction. Two signatures for cancer staging, consisting of 10 genes and 9 genes, respectively, provide high classification accuracies at 90.0% and 84.0%, among early-, advanced-stage cancer and control. Functional and pathway analyses on these signature genes reveal the significant relevance of the derived signatures to cancer grades and progression. To the best of our knowledge, this represents the first study on identification of genes whose expression patterns can serve as markers for cancer grades and stages

Changes in the distribution of red foxes (Vulpes vulpes) in urban areas in Great Britain: findings and limitations of a media-driven nationwide survey

Urbanization is one of the major forms of habitat alteration occurring at the present time. Although this is typically deleterious to biodiversity, some species flourish within these human-modified landscapes, potentially leading to negative and/or positive interactions between people and wildlife. Hence, up-to-date assessment of urban wildlife populations is important for developing appropriate management strategies. Surveying urban wildlife is limited by land partition and private ownership, rendering many common survey techniques difficult. Garnering public involvement is one solution, but this method is constrained by the inherent biases of non-standardised survey effort associated with voluntary participation. We used a television-led media approach to solicit national participation in an online sightings survey to investigate changes in the distribution of urban foxes in Great Britain and to explore relationships between urban features and fox occurrence and sightings density. Our results show that media-based approaches can generate a large national database on the current distribution of a recognisable species. Fox distribution in England and Wales has changed markedly within the last 25 years, with sightings submitted from 91% of urban areas previously predicted to support few or no foxes. Data were highly skewed with 90% of urban areas having <30 fox sightings per 1000 people km-2. The extent of total urban area was the only variable with a significant impact on both fox occurrence and sightings density in urban areas; longitude and percentage of public green urban space were respectively, significantly positively and negatively associated with sightings density only. Latitude, and distance to nearest neighbouring conurbation had no impact on either occurrence or sightings density. Given the limitations associated with this method, further investigations are needed to determine the association between sightings density and actual fox density, and variability of fox density within and between urban areas in Britain

Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius

quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and SogR1 (a LuxR homolog) interacts with OHHL to modulate transcription of specific target genes. and SOPE. and SOPE indicates the potential for neofunctionalization to occur during the process of genome degeneration

Rumination in bipolar disorder: evidence for an unquiet mind

Depression in bipolar disorder has long been thought to be a state characterized by mental inactivity. However, recent research demonstrates that patients with bipolar disorder engage in rumination, a form of self-focused repetitive cognitive activity, in depressed as well as in manic states. While rumination has long been associated with depressed states in major depressive disorder, the finding that patients with bipolar disorder ruminate in manic states is unique to bipolar disorder and challenges explanations put forward for why people ruminate. We review the research on rumination in bipolar disorder and propose that rumination in bipolar disorder, in both manic and depressed states, reflects executive dysfunction. We also review the neurobiology of bipolar disorder and recent neuroimaging studies of rumination, which is consistent with our hypothesis that the tendency to ruminate reflects executive dysfunction in bipolar disorder. Finally, we relate the neurobiology of rumination to the neurobiology of emotion regulation, which is disrupted in bipolar disorder

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells