Gene expression profiling in the adult Down syndrome brain.

The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear. We used whole genome microarrays to characterize for the first time the transcriptome of human adult brain tissue (dorsolateral prefrontal cortex) from seven DS subjects and eight controls. These data were coanalyzed with a publicly available dataset from fetal DS tissue and functional profiling was performed to identify the biological processes central to DS and those that may be related to late onset pathologies, particularly Alzheimer disease neuropathology. A total of 685 probe sets were differentially expressed between adult DS and control brains at a stringent significance threshold (adjusted p value (q) < 0.005), 70% of these being up-regulated in DS. Over 25% of genes on chromosome 21 were differentially expressed in comparison to a median of 4.4% for all chromosomes. The unique profile of up-regulation on chromosome 21, consistent with primary dosage effects, was accompanied by widespread transcriptional disruption. The critical Alzheimer disease gene, APP, located on chromosome 21, was not found to be up-regulated in adult brain by microarray or QPCR analysis. However, numerous other genes functionally linked to APP processing were dysregulated. Functional profiling of genes dysregulated in both fetal and adult datasets identified categories including development (notably Notch signaling and Dlx family genes), lipid transport, and cellular proliferation. In the adult brain these processes were concomitant with cytoskeletal regulation and vesicle trafficking categories, and increased immune response and oxidative stress response, which are likely linked to the development of Alzheimer pathology in individuals with DS.

Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.

Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology to determine the expression of approximately 22,000 mRNA transcripts in post-mortem tissue from two brain regions in patients with bipolar disorder and matched healthy controls. Dorsolateral prefrontal cortex tissue from a cohort of 70 subjects and orbitofrontal cortex tissue from a separate cohort of 30 subjects was investigated. The final analysis included 30 bipolar and 31 control subjects for the dorsolateral prefrontal cortex and 10 bipolar and 11 control subjects for the orbitofrontal cortex. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing. In the orbitofrontal cortex, 393 differentially expressed transcripts were identified by microarray analysis and a representative subset was validated by quantitative real-time PCR. Pathway analysis revealed significant upregulation of genes involved in G-protein coupled receptor signalling and response to stimulus (in particular the immune response), while genes relating to the ubiquitin cycle and intracellular transport showed coordinated downregulation in bipolar disorder. Additionally, several genes involved in synaptic function were significantly downregulated in bipolar disorder. No significant changes in gene expression were observed in the dorsolateral prefrontal cortex using microarray analysis or quantitative real-time PCR. Our findings implicate the orbitofrontal cortex as a region prominently involved in bipolar disorder and indicate that diverse processes are affected. Overall, our results suggest that dysregulation of the ubiquitin pathway and synaptic function may be central to the disease process.

Echinorhynchus brayi n. sp. (Acanthocephala: Echinorhynchidae) from Pachycara crassiceps (Roule) (Zoarcidae), a deep-sea fish.

Echinorhynchus brayi n. sp. (Palaeacanthocephala: Echinorhynchidae) is described from Pachycara crassiceps (Roule) (Zoarcidae) from the Porcupine Seabight, Northeast Atlantic. The new species closely resembles E. canyonensis Huffman & Kliever, 1977, a parasite of a Pacific zoarcid, but has longer lemnisci, larger eggs and larger testes. E. brayi n. sp. can be readily differentiated from the ten other Echinorhynchus spp. recorded from deep-sea fishes (E. abyssicola, E. gadi, E. longiproboscis, E. malacocephali, E. melanoglaeae, E. muraenolepisi, E. petrotschenkoi, E. sebastolobi, E. trachyrinci and E. truttae), because it has fewer hooks per longitudinal row.

Health care professionals and industry: reducing conflicts of interest and established best practices.

The relationship between health care providers and pharmaceutical companies and other commercial interests is ethically complex. The common practice of gift giving takes many forms including free samples, sponsorship of medical education, loan of equipment, and gifts ranging from those of nominal value such as pens to more valuable gifts such as golf outings or dinners. Gift giving is a practice that serves both the recipient and the giver, but, in the medical setting, it raises the question of whether this is to the detriment of patient care. Although health care professionals may believe they are able to ignore influence from commercial interests, human judgment research indicates that decision-makers are generally unaware of biases affecting their decisions. This is an issue of organizational ethics as well. Institutions that allow commercial interests to give some form of gift are allowing the appearance of bias as well as placing the burden of avoiding bias on the individual rather than on the institution. Conflict-of-interest analysis indicates that best practice is to limit or eliminate the influence of commercial interests, ensuring that professionals are better able to exercise their independent objective judgment.