Recommendation engines: data-driven self-help is the future of the internet

But 'augmented introspection' will be impossible if technology is driven to discover and exploit user insecurities, writes Michael Schrag

HIV seroprevalence among homeless patients admitted to a psychiatric inpatient unit

OBJECTIVE: This study was conducted to determine the seroprevalence of HIV-1 antibodies among hospitalized homeless mentally ill patients. METHOD: From December 1989 through May 1991 the authors collected discard blood samples from patients consecutively admitted to a psychiatric unit designated for the care of severely mentally ill persons removed from the streets of New York City. The blood samples were tested for HIV-1 antibodies, and the results were analyzed for associations with age, gender, ethnicity, male homosexual activity, and use of injected drugs. RESULTS: The HIV seroprevalence was 6.4% (13 of 203 samples). Patients between ages 18 and 39 accounted for 51.2% of the admissions and 84.6% of the 13 positive results, a seroprevalence of 10.6% for this subsample. Patients under age 40 were more than six times as likely to test positive for HIV antibodies as those 40 or over. Ethnicity did not predict seropositivity. Women were as likely as men to be infected. Although clinicians had noted high-risk behavior on the charts for only three (23.1%) of the 13 positive cases, a recorded history of use of injected drugs was associated with a 6.5-fold greater risk of HIV seropositivity. CONCLUSIONS: One in every 16 patients admitted to the special unit was HIV positive. Age under 40 and use of injected drugs were strongly associated with seropositivity. Because information on high-risk behavior was infrequent, the reasons for younger patients' greater risk are unclear. The homeless mentally ill require outreach efforts to reduce the risk of acquiring or transmitting HIV

ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure

Context: The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging. Objective: To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs)with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations. Design: Case-control genetic association study that included 2 control groups (lacking an established optimal control group). Setting: Semistructured psychiatric interviews. Participants: A total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample. Main Outcome Measure: Lifetime heroin dependence. Results: Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P≥.01); a similar comparison with neighborhood controls revealed greater differences (P≥1.8×10-4). Comparing cases (n=1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n=340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio=1.59; 95% CI, 1.32-1.92; P=9.7×10-7), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n=191) and nondependent (n=340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P=2.7×10-9 for the risk-associated linear trend). Conclusions: Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence

Science Literacy: Using Research-Based Facts to Make Real-World Decisions

Science Literacy: Using Research-Based Facts to Make Real-World Decisions As the next generation of leaders is entering the educational pipeline, it’s important to have an emphasis on science, technology, engineering and mathematics (STEM) to solve the grand challenge of feeding 9 billion people by 2050

Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver

Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4+ T cells expressing the CXC chemokine receptor (CXCR)3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC) which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin- coated vesicles to CD4+ T cells leading to enhanced transmigration of CXCR4+ total CD4+ T cells and CXCR3+ effector/memory CD4+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4+ T-cell transmigration in vitro as well as migration of CD4+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3+ CD4+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular transport mechanisms thereby contributing to the hepatic recruitment of CD4+ T-cell populations during immune surveillance and liver inflammation

The experimental power of FR900359 to study Gq-regulated biological processes.

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq

Villous B Cells of the Small Intestine Are Specialized for Invariant NK T Cell Dependence

B cells are important in mucosal microbial homeostasis through their well-known role in secretory IgA production and their emerging role in mucosal immunoregulation. Several specialized intraintestinal B cell compartments have been characterized, but the nature of conventional B cells in the lamina propria is poorly understood. In this study, we identify a B cell population predominantly composed of surface IgM+IgD+cells residing in villi of the small intestine and superficial lamina propria of the large intestine, but distinct from the intraepithelial compartment or organized intestinal lymphoid structures. Small intestinal (villous) B cells are diminished in genotypes that alter the strength of BCR signaling (Bruton tyrosine kinasexid, Gαi2−/−), and in mice lacking cognate BCR specificity. They are not dependent on enteric microbial sensing, because they are abundant in mice that are germfree or genetically deficient in TLR signaling. However, villous B cells are reduced in the absence of invariant NK T cells (Jα18−/− or CD1d−/− mice). These findings define a distinct population of conventional B cells in small intestinal villi, and suggest an immunologic link between CD1-restricted invariant NK T cells and this B cell population

A Cell-Permeable Inhibitor to Trap Gαq Proteins in the Empty Pocket Conformation

In spite of the crucial role of heterotrimeric G proteins as molecular switches transmitting signals from G protein-coupled receptors, their selective manipulation with small molecule, cell-permeable inhibitors still remains an unmet challenge. Here, we report that the small molecule BIM-46187, previously classified as pan-G protein inhibitor, preferentially silences Gαq signaling in a cellular context-dependent manner. Investigations into its mode of action reveal that BIM traps Gαq in the empty pocket conformation by permitting GDP exit but interdicting GTP entry, a molecular mechanism not yet assigned to any other small molecule Gα inhibitor to date. Our data show that Gα proteins may be “frozen” pharmacologically in an intermediate conformation along their activation pathway and propose a pharmacological strategy to specifically silence Gα subclasses with cell-permeable inhibitors

Verbleib von Soziologie-AbsolventInnen der Philipps-Universität Marburg

Soziologie ist an der Philipps-Universität in den 1960er Jahren als akademisches Studienfach entstanden und ab 1972 ausgebaut worden. Neben den beiden Kernbereichen 'Soziologische Theorien' und 'Methoden empirischer Sozialforschung' konnten Studierende Ende der 1990er Jahre zwischen sechs speziellen Soziologien ihre Schwerpunktsetzung wählen. Nach 30 Jahren Soziologie-Studium in Marburg erschien es sinnvoll, Daten und Informationen über den Verbleib der bisherigen Absolventinnen und Absolventen zusammenzutragen. Dieser Aufgabe stellte sich eine Gruppe von Soziologiestudierenden im Grundstudium (2./3. bzw. 3./4. Fachsemester) zusammen mit ihrem Tutor und ihrer Dozentin im Rahmen eines über zwei Semester laufenden Empirischen Praktikums (Oktober 2003 bis Juli 2004). In Anlehnung an Verbleibs- und Studienabbruchs-Studien anderer Hochschulen wurden Fragestellungen für verschiedene Teiluntersuchungen und Erhebungsinstrumente entwickelt, Interviewtechniken trainiert, Daten erhoben und quantitativ bzw. qualitativ ausgewertet sowie der abschließende Forschungsbericht geschrieben. Die Grundgesamtheit wurde (wegen der schwierigen Adressrecherche) auf die Abschlussjahrgänge 1990 bis 2003 beschränkt. Durchgeführt wurden: eine postalische Fragebogenuntersuchung aller erreichbaren AbsolventInnen (realisiert 88 Befragungen); drei berufsbiografische Interviews mit AbsolventInnenen der Jahre 1991-1996-2001; vier perspektivische Leitfadeninterviews (problemzentriert) mit AbsolventInnen des Jahres 2003; zwei Leitfadeninterviews mit einem Abbrecher bzw. einem Studienfachwechsler; Experteninterviews mit potenziellen ArbeitgebervertreterInnen. Für die Analysen wurden je nach Datenstandard statistische Verfahren, qualitative Inhaltsanalyse oder sequenzielle Analyse eingesetzt. Die Befunde ermöglichen Einschätzungen hinsichtlich der damaligen Diplom- und Magisterstudiengänge in Marburg - hinsichtlich Bachelor- und Master-Studiengängen oder für andere Hochschulen müsste eine Studie entsprechend modifiziert werden

World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections

Peer reviewe