Conditional deletion of Ccm2 causes hemorrhage in the adult brain: a mouse model of human cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are irregularly shaped and enlarged capillaries in the brain that are prone to hemorrhage, resulting in headaches, seizures, strokes and even death in patients. The disease affects up to 0.5% of the population and the inherited form has been linked to mutations in one of three genetic loci, CCM1, CCM2 and CCM3.

Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues.

Serotonin (5-HT) controls affective and motivational aspects of palatable food and drug reward and the 5-HT(2C) receptor (5-HT(2C)R) has emerged as a key regulator in this regard. We have evaluated the efficacy of a selective 5-HT(2C)R agonist, WAY 163909, in cocaine and sucrose self-administration and reinstatement assays employing parallel experimental designs in free-fed rats. WAY 163909 dose-dependently reduced the reinforcing efficacy of cocaine (ID(50) = 1.

Parent understanding of the role of doctors and doctors in training on an inpatient pediatric ward.

Background: Many physician trainees care for patients in an academic hospital. We studied parent understanding of the roles of medical students, interns, residents, and attending physicians in the inpatient setting of a children's hospital.

Description: Surveys were given to parents during a hospital stay on a medical service asking about the responsibilities and education of physicians and trainees.

Serotonin (5-hydroxytryptamine) 5-HT(2A) receptor: association with inherent and cocaine-evoked behavioral disinhibition in rats.

Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT(2A) receptor (5-HT(2A)R) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine.

Acidic calcium stores of Saccharomyces cerevisiae.

Fungi and animals constitute sister kingdoms in the eukaryotic domain of life. The major classes of transporters, channels, sensors, and effectors that move and respond to calcium ions were already highly networked in the common ancestor of fungi and animals. Since that time, some key components of the network have been moved, altered, relocalized, lost, or duplicated in the fungal and animal lineages and at the same time some of the regulatory circuitry has been dramatically rewired.

Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors.

Background: Philadelphia chromosome (Ph)-positive B-lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy.

Methods: The authors studied 65 adult patients with Ph-positive acute lymphoblastic leukemia (ALL) who received treatment with TKI-based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with those from 60 adult patients with diploid B-cell ALL who received similar chemotherapy without a TKI.

New regulators of a high affinity Ca2+ influx system revealed through a genome-wide screen in yeast.

The bakers' yeast Saccharomyces cerevisiae utilizes a high affinity Ca(2+) influx system (HACS) to survive assaults by mating pheromones, tunicamycin, and azole-class antifungal agents. HACS consists of two known subunits, Cch1 and Mid1, that are homologous and analogous to the catalytic α-subunits and regulatory α2δ-subunits of mammalian voltage-gated calcium channels, respectively. To search for additional subunits and regulators of HACS, a collection of gene knock-out mutants was screened for abnormal uptake of Ca(2+) after exposure to mating pheromone or to tunicamycin.

Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent subjects.

Background: Cocaine-dependent subjects show attentional bias to cocaine-related stimuli, increased impulsivity on questionnaires, and impaired inhibitory control (one component of impulsivity on behavioral tasks). However, the relationship between attentional bias, impulsivity, and inhibitory control in cocaine-dependent subjects is unknown.

Objective: To investigate the relationship between attentional bias to cocaine-related stimuli, impulsivity, and inhibitory control in cocaine dependence.

Generation of priority research questions to inform conservation policy and management at a national level.

Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans.

Estrogens of multiple classes and their role in mental health disease mechanisms.

Gender and sex hormones can influence a variety of mental health states, including mood, cognitive development and function, and vulnerability to neurodegenerative diseases and brain damage. Functions of neuronal cells may be altered by estrogens depending upon the availability of different physiological estrogenic ligands; these ligands and their effects vary with life stages, the genetic or postgenetic regulation of receptor levels in specific tissues, or the intercession of competing nonphysiological ligands (either intentional or unintentional, beneficial to health or not). Here we review evidence for how different estrogens (physiological and environmental/dietary), acting via different estrogen receptor subtypes residing in alternative subcellular locations, influence brain functions and behavior.

Quantification of RNA editing of the serotonin 2C receptor (5-HT(₂C)R) ex vivo.

The 5-HT(₂C)R receptor (5-HT(₂C)R) exerts tonic and phasic inhibitory influence over brain circuitry, and dysregulation of this influence contributes to the neurochemical underpinnings in the etiology of a variety of neuropsychiatric disorders including addiction, depression, and schizophrenia. A strategically important regulator of the 5-HT(₂C)R function and protein diversity is mRNA editing, a type of posttranscriptional modification that alters codon identity and thus the translation of distinct, though closely related, isoforms of 5-HT(₂C)R from a single, original transcript. The 5-HT(₂C)R mRNA can be edited at five closely spaced sites, altering the identity of up to three amino acids in the predicted second intracellular loop of the receptor to modulate receptor:G-protein coupling and constitutive activity.

Aflatoxin and PAH exposure biomarkers in a U.S. population with a high incidence of hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) is significantly elevated in a Hispanic community in Bexar County, Texas. Chronic exposure to dietary aflatoxins (AFs) is a major risk factor for HCC; increased risk has been linked to polycyclic aromatic hydrocarbon (PAH) co-exposure and hepatitis virus infection. The aims of this study were to assess AF and PAH exposures, investigate dietary factors that may contribute to increased AF exposure, and determine the prevalence of hepatitis virus infection in Bexar Co.

Facial motor nuclei cell loss with intratemporal facial nerve crush injuries in rats.

Objectives/hypothesis: Injuries of cranial nerves that are distal to but near the motor nucleus might result in retrograde motoneuron cell death. The hypothesis of this article is that an intratemporal crush injury of the facial nerve in rats can cause facial motor nuclei cell death.

Study Design: Prospective, randomized, controlled animal study.

Multiple ice-age refugia in Pacific cod, Gadus macrocephalus.

Pleistocene ice-ages greatly influenced the historical abundances of Pacific cod, Gadus macrocephalus, in the North Pacific and its marginal seas. We surveyed genetic variation at 11 microsatellite loci and mitochondrial (mt) DNA in samples from twelve locations from the Sea of Japan to Washington State. Both microsatellite (mean H = 0.

Plerixafor mobilization leads to a lower ratio of CD34+ cells to total nucleated cells which results in greater storage costs.

Background: Plerixafor (Mozobil, AMD3100) with granulocyte-colony stimulating factor (G-CSF) mobilizes more CD34+ cells/kg compared to G-CSF alone. Given that plerixafor enhances mobilization of multiple white blood cell lineages, we determined if more storage space is required for products collected from patients mobilized with plerixafor.

Methods: A review of the medical records of 15 patients mobilized with chemotherapy and G-CSF (control) and 14 patients mobilized with plerixafor plus G-CSF (plerixafor) was performed.

Complement C3a, CpG oligos, and DNA/C3a complex stimulate IFN-α production in a receptor for advanced glycation end product-dependent manner.

The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor implicated in a number of diseases including autoimmune diseases. To further understand the pathogenic mechanism of RAGE in these diseases, we searched for additional ligands. We discovered that C3a bound to RAGE with an EC(50) of 1.

Proximity to the US-Mexico border: a key to explaining geographic variation in US methamphetamine, cocaine and heroin purity.

Aims: Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity.

Design: Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004.

CD4+ T cells reduce the tissue burden of Chlamydia muridarum in male BALB/c mice.

Male chlamydial infections are becoming more recognised as an aetiological agent in infertility. An IFN-gamma response is required for protection against Chlamydia in females, but may have the potential to induce pathology in the immune-privileged male reproductive tract. We examined the induction of immunity following intranasal immunisation with major outer membrane protein (MOMP) of Chlamydia muridarum in male BALB/c mice, and the role of MOMP-specific CD4+ T cells in clearance of an intrapenile infection.

Chlamydia muridarum major outer membrane protein-specific antibodies inhibit in vitro infection but enhance pathology in vivo.

Problem: Chlamydia trachomatis is a significant worldwide health problem, and the often-asymptomatic disease can result in infertility. To develop a successful vaccine, a complete understanding of the immune response to chlamydial infection and development of genital tract pathology is required.

Method Of Study: We utilized the murine genital model of chlamydial infection.

Physical activity, exercise and low-grade systemic inflammation.

Prospective studies have shown that chronic low-grade inflammation may contribute to the pathogenesis of the most common chronic diseases and in particular CVD. Obesity has repeatedly been associated with moderately raised levels of inflammation, and this observation has led to the view that obesity is characterised by a state of chronic low-grade inflammation. There is now great interest in elucidating how physical activity and exercise modulate inflammation.

Gastrointestinal targets of appetite regulation in humans.

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies.

Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen.

Lenalidomide is an active treatment for multiple myeloma (MM) and is increasingly used as part of the initial treatment of this disease. Recent reports have suggested decreases in the number of CD34+ cells collected and increases in the failure rate among patients whose initial therapy contained lenalidomide when mobilized with G-CSF alone. A retrospective data analysis of 364 patients with MM who underwent stem cell mobilization and attempted harvest at the Hospital of the University of Pennsylvania between January 2002 and December 2007 was performed.