Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment

ABSTRACTVascular cognitive impairment (VCI) is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651). The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively). In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction

What determines auditory similarity? The effect of stimulus group and methodology.

Two experiments on the internal representation of auditory stimuli compared the pairwise and grouping methodologies as means of deriving similarity judgements. A total of 45 undergraduate students participated in each experiment, judging the similarity of short auditory stimuli, using one of the methodologies. The experiments support and extend Bonebright's (1996) findings, using a further 60 stimuli. Results from both methodologies highlight the importance of category information and acoustic features, such as root mean square (RMS) power and pitch, in similarity judgements. Results showed that the grouping task is a viable alternative to the pairwise task with N > 20 sounds whilst highlighting subtle differences, such as cluster tightness, between the different task results. The grouping task is more likely to yield category information as underlying similarity judgements

c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines

It is widely accepted that the c-Fos gene has a role in proliferation and differentiation of bone cells. ATP-induced c-Fos activation is relevant to bone homeostasis, because nucleotides that are present in the environment of bone cells can contribute to autocrine/paracrine signalling. Gut hormones have previously been shown to have an effect on bone metabolism. In this study, we used the osteoblastic Saos-2 cell line transfected with a c-Fos-driven reporter stimulated with five gut hormones: glucose inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), ghrelin and obestatin, in the presence or absence of ATP. In addition, TE-85 cells were used to determine the time course of c-Fos transcript induction following stimulation with GLP-1, and GLP-2 with or without ATP, using reverse transcription qPCR. The significant results from the experiments are as follows: higher level of c-Fos induction in presence of GIP, obestatin (p = 0.019 and p = 0.011 respectively), and GIP combined with ATP (p < 0.001) using the luciferase assay; GLP-1 and GLP-2 combined with ATP (p = 0.034 and p = 0.002, respectively) and GLP-2 alone (p < 0.001) using qPCR. In conclusion, three of the gut peptides induced c-Fos, providing a potential mechanism underlying the actions of these hormones in bone which can be directed or enhanced by the presence of ATP

Dissolved inorganic nutrients and chlorophyll on the narrow continental shelf of Eastern Brazil

The eastern Brazilian continental shelf is narrow and subject to the influence of a western boundary current system, presenting lower biological productivity than other regions. In this study, the distribution of water masses, dissolved inorganic nutrients, chlorophyll-a and total suspended solids (TSS) on the inner shelf (< 35 m depth), between Itacaré and Canavieiras, eastern Brazil, is presented. Sampling surveys were carried out in March and August 2006 and March 2007. Tropical water (TW) prevailed during March 2006 and August 2007 with the lower salinity waters (< 36) found in most samples taken in March 2007, reflecting the influence of continental outflow and rain in coastal waters. Low concentrations of dissolved inorganic nutrients and Chl-a found were typical of TW and results suggested that the inner shelf waters were depleted in dissolved inorganic nitrogen in August 2006 and March 2007, and in phosphate in March 2006, potentially affecting phytoplankton growth. Stratification of the water column was observed due to differences in dissolved nutrient concentrations, chlorophyll-a and TSS when comparing surface and bottom samples, possibly the result of a colder water intrusion and mixing on the bottom shelf and a deep chlorophyll maximum and/or sediment resuspension effect. Despite this stratification, oceanographic processes such as lateral mixing driven by the Brazil Current as well as a northward alongshore drift driven by winds and tides transporting Coastal Water can lead to an enhanced mixing of these waters promoting some heterogeneity in this oligotrophic environment

A Novel Mouse c-fos Intronic Promoter That Responds to CREB and AP-1 Is Developmentally Regulated In Vivo

BACKGROUND: The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene

A genome-wide DNA methylation study in colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC).</p> <p>Methods</p> <p>We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center.</p> <p>Results</p> <p>We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application.</p> <p>Conclusion</p> <p>Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.</p