Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Higgs mass and vacuum stability in the Standard Model at NNLO

We present the first complete next-to-next-to-leading order analysis of the Standard Model Higgs potential. We computed the two-loop QCD and Yukawa corrections to the relation between the Higgs quartic coupling (lambda) and the Higgs mass (Mh), reducing the theoretical uncertainty in the determination of the critical value of Mh for vacuum stability to 1 GeV. While lambda at the Planck scale is remarkably close to zero, absolute stability of the Higgs potential is excluded at 98% C.L. for Mh < 126 GeV. Possible consequences of the near vanishing of lambda at the Planck scale, including speculations about the role of the Higgs field during inflation, are discussed.Comment: 35 pages, 8 figures. Final published version, misprints fixed, figures update

Ordering phenomena in quasi one-dimensional organic conductors

Low-dimensional organic conductors could establish themselves as model systems for the investigation of the physics in reduced dimensions. In the metallic state of a one-dimensional solid, Fermi-liquid theory breaks down and spin and charge degrees of freedom become separated. But the metallic phase is not stable in one dimension: as the temperature is reduced, the electronic charge and spin tend to arrange themselves in an ordered fashion due to strong correlations. The competition of the different interactions is responsible for which broken-symmetry ground state is eventually realized in a specific compound and which drives the system towards an insulating state. Here we review the various ordering phenomena and how they can be identified by optic and magnetic measurements. While the final results might look very similar in the case of a charge density wave and a charge-ordered metal, for instance, the physical cause is completely different. When density waves form, a gap opens in the density of states at the Fermi energy due to nesting of the one-dimension Fermi surface sheets. When a one-dimensional metal becomes a charge-ordered Mott insulator, on the other hand, the short-range Coulomb repulsion localizes the charge on the lattice sites and even causes certain charge patterns. We try to point out the similarities and conceptional differences of these phenomena and give an example for each of them. Particular emphasis will be put on collective phenomena which are inherently present as soon as ordering breaks the symmetry of the system.Comment: Review article Naturwissenschaften 200

The study design of UDRIVE: the Naturalistic Driving Study across Europe for cars, trucks and scooters

Purpose: UDRIVE is the first large-scale European Naturalistic Driving Study on cars, trucks and powered two wheelers. The acronym stands for "European naturalistic Driving and Riding for Infrastructure & Vehicle safety and Environment". The purpose of the study is to gain a better understanding of what happens on the road in everyday traffic situations. Methods: The paper describes Naturalistic Driving Studies, a method which provides insight into the actual real-world behaviour of road users, unaffected by experimental conditions and related biases. Naturalistic driving can be defined as a study undertaken to provide insight into driver behaviour during everyday trips by recording details of the driver, the vehicle and the surroundings through unobtrusive data gathering equipment and without experimental control. Data collection will take place in six EU Member States. Results: Road User Behaviour will be studied with a focus on both safety and environment. The UDRIVE project follows the steps of the FESTA-V methodology, which was originally designed for Field Operational Tests. Conclusions: Defining research questions forms the basis of the study design and the specification of the recording equipment. Both will be described in this paper. Although the project has just started collecting data from drivers, we consider the process of designing the study as a major result which may help other initiatives to set up similar studies

Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

Benign thyroid disease and dietary factors in thyroid cancer: a case-control study in Kuwait

We conducted a population-based study of 313 case–control pairs in Kuwait to examine the aetiology of thyroid cancer, the second most common neoplasm among women in this and several other countries in the Gulf region. Among the demographic variables, individuals with 12+ years of education had a significantly reduced risk of thyroid cancer (OR=0.6; 95% CI: 0.3–0.9). The average age at diagnosis (s.d.) of thyroid cancer was 34.711 years in women and 3913.4 years in men. History of thyroid nodule was reported only by cases (n=34; 10.9%; lower 95% CI: 12.0); and goitre by 21 cases and four controls (OR=5.3; 95% CI: 1.8–15.3). There was no significant increase in risk with history of hypothyroidism (OR=1.8) or hyperthyroidism (OR=1.7). For any benign thyroid disease, the OR was 6.4 (95% CI: 3.4–12.0); and the population attributable risk was about 26% (95% CI: 21.1–30.9). Stepwise regression analysis showed that high consumption of processed fish products (OR=2.2; 95% CI: 1.6–3.0) fresh fish (OR=0.5; 95% CI: 0.4–0.7) and chicken (OR=1.7; 95% CI: 1.2–2.3) were independently associated with thyroid cancer with significant dose-response relationships. Among the thyroid cancer patients who reported high consumption of fish products, a large majority also reported high consumption of fresh fish (98%) and shellfish (68%). No clear association emerged with consumption of cruciferous vegetables. These data support the hypothesis that hyperplastic thyroid disease is strongly related to thyroid cancer; and that habitual high consumption of various seafoods may be relevant to the aetiology of thyroid cancer. The association with chicken consumption requires further study

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany

<p>Abstract</p> <p>Background</p> <p>In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster.</p> <p>Methods</p> <p>Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines.</p> <p>Results</p> <p>The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally.</p> <p>Conclusion</p> <p>The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.</p

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse