MicroRNA 125b inhibition of B cell differentiation in germinal centers.

MicroRNAs 125a and 125b are predicted to be able to bind to the B lymphocyte-induced maturation protein-1 (BLIMP-1) and IFN regulatory protein-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation. A computational survey of the human and mouse genomes revealed that miR-125a and miR-125b are members of a multigene family located in paralogous clusters. The miR-125a cluster on chromosome 19 in humans includes miR-99b and let-7e, whereas the miR-125b cluster on chromosome 21 includes miR-99a and miR-let-7c.

Feasible and successful: genome-wide interaction analysis involving all 1.9 x 10(11) pair-wise interaction tests.

The Genome-Wide Association Study (GWAS) is the study design of choice for detecting common genetic risk factors for multifactorial diseases. The performance of full Genome-Wide Interaction Analyses (GWIA) has always been considered computationally challenging. Two-stage strategies to reduce the amount of numerical analysis require the detection of single marker effects or prior pathophysiological hypotheses before the analysis of interaction.

Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology.

Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands.

Whole-genome linkage scan for epilepsy-related photosensitivity: a mega-analysis.

Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide linkage studies have been published before and they identified loci for PPR at 6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with additional families, in a mega-analysis of 100 families.

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT.

The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics.

Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies.

Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.

Gastrocnemius tightness on joint angle and work of lower extremity during gait.

Background: Muscular tightness is a common clinical musculoskeletal disorder and is regarded as a predisposing factor for muscle injuries. In this study, a two-way mixed design ANOVA was applied to investigate the effects of the gastrocnemius tightness on the joint angle and joint work during walking.

Methods: Twenty-two patients with muscular tightness of gastrocnemius muscle (<12 degrees of ankle dorsiflexion with knee extended) and 22 age- and gender-matched subjects with normal gastrocnemius flexibility (>15 degrees of ankle dorsiflexion with knee extended) participated in this study.

Design, synthesis, and biological evaluation of 16-substituted 4-azasteroids as tissue-selective androgen receptor modulators (SARMs).

A novel series of 16-substituted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential, and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in the OVX and ORX rat models and exhibited an osteoanabolic, tissue-selective profile.

Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance.

Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.

Perceived mental illness stigma and HIV risk behaviors among adult psychiatric outpatients in Rio de Janeiro, Brazil.

We examined the associations between perceived mental illness stigma and HIV risk and protective behaviors among adults with severe mental illness (SMI) in Rio de Janeiro, Brazil. We measured mental illness stigma across three domains ("Personal Experiences," "Perceived Attractiveness," and "Relationship Discrimination"), and examined the relationship between experiences of stigma in each domain and HIV risk and protective behaviors over the past 3 months in 98 outpatients with SMI. Those who reported greater "Relationship Discrimination" stigma were significantly more likely to be sexually active and to have unprotected sex; they were significantly less likely to report deliberately having fewer partners as a way to protect themselves from HIV.

Rates and types of psychiatric disorders in perinatally human immunodeficiency virus-infected youth and seroreverters.

Background: The purpose of this study was to examine 1) the prevalence of psychiatric and substance use disorders in perinatally HIV-infected (HIV+) adolescents and 2) the association between HIV infection and these mental health outcomes by comparing HIV+ youths to HIV exposed but uninfected youths (HIV-) from similar communities.

Methods: Data for this paper come from the baseline interview of a longitudinal study of mental health outcomes in 9-16 year old perinatally HIV-exposed youths (61% HIV+) and their caregivers. Three hundred forty youths and their primary adult caregivers were recruited from four medical centers and participated in separate individual interviews.

The development and validation of a tool to assess nurse performance in dual protection counseling.

Objective: To present preliminary evidence for the reliability and validity of the Dual Protection Counseling Checklist (DPCC), an instrument designed to evaluate nurses' fidelity to high quality dual protection counseling in a family planning setting.

Methods: During a trial comparing a dual protection (DP) nurse counseling intervention to standard of care (SOC), client-counselor sessions were audiotaped. Following good inter-rater reliability, 78 audiotaped interviews were coded from the two conditions using the DPCC.

Solute migration caused by excited state absorptions.

Using the Z-scan technique, we find that migration of chloroaluminum phthalocyanine in liquid ethanol can be induced by the absorption of a 19 ps laser pulse with energy exceeding a threshold but not by that of a 2.8 ns pulse depositing more energy at the solute molecules. Considering each solute molecule as an oscillator confined within a potential well, we explain, in accordance with the five-energy-band model, that solute molecules excited by a 19 ps pulse retain more translational excess energy to overcome the potential well barrier compared with those excited by a 2.

15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.

We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)).

20-Hydroxyeicosatetraenoic acid inhibits the apoptotic responses in pulmonary artery smooth muscle cells.

20-Hydroxyeicosatetraenoic acid (20-HETE), a omega-hydroxylation product of arachidonic acid catalyzed by cytochrome P450 4A (CYP4A), plays a role in vascular smooth muscle remodeling. Although its effects on angiogenic responses are known, it remains unclear whether 20-HETE acts on apoptosis of pulmonary arterial smooth muscle cells (PASMC), an important step in PASMC remodeling, and what pathways are involved in the process. Here we show evidence for the missing information.

A regulatory circuit mediating convergence between Nurr1 transcriptional regulation and Wnt signaling.

The orphan nuclear receptor Nurr1 is essential for the development and maintenance of midbrain dopaminergic neurons, the cells that degenerate during Parkinson's disease, by promoting the transcription of genes involved in dopaminergic neurotransmission. Since Nurr1 lacks a classical ligand-binding pocket, it is not clear which factors regulate its activity and how these factors are affected during disease pathogenesis. Since Wnt signaling via beta-catenin promotes the differentiation of Nurr1(+) dopaminergic precursors in vitro, we tested for functional interactions between these systems.

Constituents from the leaves of Phellodendron amurense and their antioxidant activity.

Three new coumarins, phellodenols F-H (1-3) and a new glutaric acid derivative, phellodendric acid-A (4) were isolated from the leaves of Phellodendron amurense together with twenty-nine known compounds. Extensive 1D and 2D NMR experiments and other spectroscopic studies were employed to determine the structures of 1-4. The isolated compounds were screened for their antioxidant activity through DPPH (alpha,alpha-diphenyl-beta-picrylhydrazyl) radical scavenging assay.

Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy.

Potent bisphosphonates (BPs) preferentially bind bone at sites of active osteoclastic bone resorption, where they are taken up by the osteoclast and inhibit resorption. We tested the hypothesis that BP affinity to human bone affects antiresorptive potency. [(1)(4)C]-Alendronate binding to human bone was saturable and reversible with an apparent Kd of 72 microM by Scatchard analysis.

Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells.

The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4- memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation.

Comparison of atrazine losses in three small headwater catchments.

Understanding the processes causing herbicide transport to surface waters is crucial to determine mitigation options to reduce these losses. To this end, we investigated the atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) transport in three agricultural catchments (1.1-2.

The impact of substance dependence on HIV sexual risk-reduction among men with severe mental illness.

We explored the impact of substance dependence on the efficacy of an HIV sexual risk reduction intervention previously shown to be effective among men with severe mental illness by comparing rates of high-risk sexual behaviors among men with (n = 26) and without (n = 31) a lifetime history of substance dependence. We sub-divided subjects by alcohol and drug dependence status, comparing each intervention sub-group to the corresponding control sub-group. At each follow-up interval (six, 12 and 18 months), the intervention group as a whole and the non-substance dependent participants showed a significant reduction in risk; the substance-dependent men showed no difference from controls.