Genome-Wide Identification of Calcium-Response Factor (CaRF) Binding Sites Predicts a Role in Regulation of Neuronal Signaling Pathways

Calcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no homology with other transcription factors, its properties and gene targets have remained unknown. Here we show that the DNA binding domain of CaRF has been highly conserved across evolution and that CaRF binds DNA directly in a sequence-specific manner in the absence of other eukaryotic cofactors. Using a binding site selection screen we identify a high-affinity consensus CaRF response element (cCaRE) that shares significant homology with the CaRE1 element of Bdnf. In a genome-wide chromatin immunoprecipitation analysis (ChIP-Seq), we identified 176 sites of CaRF-specific binding (peaks) in neuronal genomic DNA. 128 of these peaks are within 10kB of an annotated gene, and 60 are within 1kB of an annotated transcriptional start site. At least 138 of the CaRF peaks contain a common 10-bp motif with strong statistical similarity to the cCaRE, and we provide evidence predicting that CaRF can bind independently to at least 64.5% of these motifs in vitro. Analysis of this set of putative CaRF targets suggests the enrichment of genes that regulate intracellular signaling cascades. Finally we demonstrate that expression of a subset of these target genes is altered in the cortex of Carf knockout (KO) mice. Together these data strongly support the characterization of CaRF as a unique transcription factor and provide the first insight into the program of CaRF-regulated transcription in neurons

Risk factors and biomarkers of life-threatening cancers

There is growing evidence that risk factors for cancer occurrence and for cancer death are not necessarily the same. Knowledge of cancer aggressiveness risk factors (CARF) may help in identifying subjects at high risk of developing a potentially deadly cancer (and not just any cancer). The availability of CARFs may have positive consequences for health policies, medical practice, and the search for biomarkers. For instance, cancer chemoprevention and cancer screening of subjects with CARFs would probably be more ethical and cost-effective than recommending chemoprevention and screening to entire segments of the population. Also, the harmful consequences of chemoprevention and of screening would be reduced while effectiveness would be optimised. We present examples of CARF already in use (e.g. mutations of the breast cancer (BRCA) gene), of promising avenues for the discovery of biomarkers thanks to the investigation of CARFs (e.g. breast radiological density and systemic inflammation), and of biomarkers commonly used that are not real CARFs (e.g. certain mammography images, prostate-specific antigen (PSA) concentration, nevus number)

Efficacy of Pain Rehabilitation Program in Reducing Depression and Perceived Pain

Clinical depression is a frequently associated mental health disorder found in patients with chronic pain. Many of the symptoms associated with chronic pain mirror the diagnostic criteria for Major Depression. For example, chronic pain often results in social isolation, withdrawal, feelings of hopelessness, sleep difficulties, loss of interest in usual activities, financial strain, and lack of energy-all of which are common symptoms of depression. The purpose of this study is to address the comorbidity between depression and chronic pain and to assess the impact of a multidisciplinary pain rehabilitation program on the level of depression and perceived pain. Changes in depression and pain are observed pre- and post- treatment using the BDI-II and a self-report measure of pain, at evaluation, day of admittance, and at discharge. This present study hypothesizes depression and perceived pain will decrease by completion of the program. The archival clinical sample was comprised of 66, Caucasian, Hispanic, and African American patients who completed a multidisciplinary pain rehabilitation program, ranging from 18 to 20 day treatment. Results indicated significant reduction of depression and perceived pain at completion of program. Outcomes support the effectiveness of multidisciplinary pain rehabilitation, and its usefulness in reducing depression and perceived pain

Coupling immunity and programmed cell suicide in prokaryotes: Life-or-death choices

Host-pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti-pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is “deemed” capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins-antitoxins, suggestive of immunity-PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR-Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD

Report of the Terrestrial Bodies Science Working Group. Volume 1: Executive summary

Current knowledge of Mercury, Venus, Mars, the Moon, asteroids, comets, and the Galilean satellites were reviewed along with related NASA programs and available mission concepts. Exploration plans for the 1980 to 1990 period are outlined and recommendations made. Topics discussed include: scientific objectives and goals, exploration strategy and recommended mission plans, supporting research and technology, Earth-based and Earth-orbital investigations, data analysis and synthesis, analysis of extraterrestrial materials, broadening the science support base, and international cooperation

Mulberry, Monkey and Weasel

pages 69-7

Behavioral Self-management in an Inpatient Headache Treatment Unit: Increasing Adherence and Relationship to Changes in Affective Distress

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74935/1/j.1526-4610.2000.00057.x.pd