Mechanism of Rab1b deactivation by the Legionella pneumophila

Legionella pneumophila is an intracellularly surviving pathogen that releases about 270 different proteins into the host cell during infection. A set of secreted proteins takes control of the vesicular trafficking regulator Rab1. Legionella LepB inactivates Rab1 by acting as a GTPase-activating protein (GAP). We present the crystal structure of the Rab1b:LepB complex together with a thorough biochemical analysis and show that the GAP domain of LepB consists of an unusual fold. LepB acts by an atypical RabGAP mechanism that is reminiscent of classical GAPs and therefore sets the protein apart from mammalian TBC-like GAPs. Surprisingly, LepB can function as a GAP for Rab3, Rab8, Rab13 and Rab35, too, suggesting that it has a broader cellular role than previously thought

Enhanced generation of VUV radiation by four-wave mixing in mercury using pulsed laser vaporization

The efficiency of a coherent VUV source at 125 nm, based on 2-photon resonant four-wave mixing in mercury vapor, has been enhanced by up to 2 orders of magnitude. This enhancement was obtained by locally heating a liquid Hg surface with a pulsed excimer laser, resulting in a high density vapor plume in which the nonlinear interaction occurred. Energies up to 5 μJ (1 kW peak power) have been achieved while keeping the overall Hg cell at room temperature, avoiding the use of a complex heat pipe. We have observed a strong saturation of the VUV yield when peak power densities of the fundamental beams exceed the GW/cm2 range, as well as a large intensity-dependant broadening (up to ~30 cm-1) of the two-photon resonance. The source has potential applications for high resolution interference lithography and photochemistry

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

Weaning practices in phenylketonuria vary between health professionals in Europe

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe

Treatment of cancer of the anal canal. The Hamburg experience

14062 Background: To compare surgical and non-surgical treatment approaches for anal cancer and to identify prognostic factors. Methods: Survival data of 214 patients with cancer of the anal canal were reviewed who were referred for radiotherapy to the Department of Radiation Oncology of the University of Hamburg, Germany between 1/88 and 3/05. 75 patients received a definitive radiochemotherapy (RCT) with 5-FU and MMC according to international standards, 43 an operation followed by RCT (OP+RCT), 37 an operation followed by irradiation (OP+RT), 25 an irradiation alone (RT) and 34 an operation alone because they refused a planned adjuvant RCT or RT. The operations had been performed by different referring hospitals in and around Hamburg. Results: The median follow-up time of the living patients was 67 months (1–200 months). The 10 year overall survival rate for RCT was 0.62 (95%CI 0.46–0.77), for OP+RCT 0.65 (95%CI 0.47–0.83), for OP+RT 0.55 (95%CI 0.37–0.74), for OP alone 0.51 (95%CI 0.26–0.75) and for RT alone 0.27 (95%CI 0.05–0.48). There was no statistical difference between the overall survival of patients who received RCT, OP+RCT and OP+RT according to Kaplan Meier analysis (log rank test, p = 0.71). Cox regression analysis was used to examine the simultaneous influence of the prognostic factors T, N, age, haemoglobin concentration before radiotherapy, gender, and grading on the survival of patients who were treated with RCT. The model (p = 0.015) revealed T and N to be the only statistically significant prognostic factors. Conclusions: The different surgical and non-surgical approaches to treat cancer of the anal canal in Hamburg obviously reflect the individual preferences of the different physicians. Statistical analysis did not show a benefit of an OP added to RCT. Prognostic factors for survival after RCT were the T- and N-stage. No significant financial relationships to disclose. </jats:p