Supramolecular organization of the human N-BAR domain in shaping the sarcolemma membrane

This is the final version of the article. Available from Elsevier via the DOI in this record.The 30 kDa N-BAR domain of the human Bin1 protein is essential for the generation of skeletal muscle T-tubules. By electron cryo-microscopy and electron cryo-tomography with a direct electron detector, we found that Bin1-N-BAR domains assemble into scaffolds of low long-range order that form flexible membrane tubules. The diameter of the tubules closely matches the curved shape of the N-BAR domain, which depends on the composition of the target membrane. These insights are fundamental to our understanding of T-tubule formation and function in human skeletal muscle.This work was supported by grants from the Deutsche Forschungsgemeinschaft (GRK 1026, SFB610) (A.A., T.G., J.B.), the BMBF ZIK program (A.M., J.B.), the European Regional Development Fund of the European Commission (A.M., T.G.: EFRE 1241 12 0001), and the state Sachsen-Anhalt (A.M., T.G., J.B.)

A temperature‐controlled, circular maintenance system for studying growth and development of pelagic tunicates (salps)

Salps have attracted attention as zooplankton organisms that may be able to expand their habitat range and increase their ecological importance in the face of ongoing global warming. Due to their gelatinous nature, unique feeding strategy, and reproductive ecology such changes could have profound impacts on regional marine ecosystems. While their role in the regional carbon cycle is receiving attention, our knowledge of their physiology and life cycle is still limited. This knowledge gap is mainly due to their fragile gelatinous nature, which makes it difficult to capture and maintain intact specimen in the laboratory. We present here a modified kreisel tank system that has been tested onboard a research vessel with the Southern Ocean salp Salpa thompsoni and at a research station with Salpa fusiformis and Thalia democratica from the Mediterranean Sea. Successful maintenance over days to weeks allowed us to obtain relative growth and developmental rates comparable to in situ field samples of S. thompsoni and S. fusiformis, and provided insights into previously unknown features of their life cycle (e.g., testes development). Our results show that traditional methods of estimating growth, such as cohort analysis, may lead to a general overestimation of growth rates and neglect individual strategies (e.g., shrinkage), which can affect the results and conclusions drawn from population dynamic models. By providing a starting point for the successful maintenance of different species, comparable experiments on the physiology of salps is made possible. This will contribute to refining model parameters and improving the reliability of the predictions

HESS Opinions: Socio-economic and ecological trade-offs of flood management – benefits of a transdisciplinary approach

In light of climate change and growing numbers of people inhabiting riverine floodplains, worldwide demand for flood protection is increasing, typically through engineering approaches such as more and bigger levees. However, the well-documented “levee effect” of increased floodplain use following levee construction or enhancement often results in increased problems, especially when levees fail or are compromised by big flood events. Herein, we argue that there are also unintended socio-economic and ecological consequences of traditional engineering solutions that need to be better considered, communicated and weighed against alternative solutions. Socio-economic consequences include reduced aesthetic and recreational values as well as increased downstream flooding risk and reduced ecosystem services. Ecological consequences include hydraulic decoupling, loss of biodiversity and increased risk of contamination during flooding. In addition, beyond river losses of connectivity and natural riparian vegetation created by levees, changes in groundwater levels and increased greenhouse gas emissions are likely. Because flood protection requires huge financial investments and results in major and persistent changes to the landscape, more balanced decisions that involve all stakeholders and policymakers should be made in the future. This requires a transdisciplinary approach that considers alternative solutions such as green infrastructure and places emphasis on integrated flood management rather than on reliance on technical protection measures.</p

Replacement therapy for bleeding episodes in factor VII deficiency: A prospective evaluation

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimalPatients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one postrFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 μg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal. © Schattauer 2013

Gang Exposure and Pregnancy Incidence among Female Adolescents in San Francisco: Evidence for the Need to Integrate Reproductive Health with Violence Prevention Efforts

Among a cohort of 237 sexually active females aged 14–19 recruited from community venues in a predominantly Latino neighborhood in San Francisco we examined the relationship between gang exposure and pregnancy incidence over two years of follow-up. Using discrete-time survival analysis we investigated whether individual and partner gang membership were associated with pregnancy incidence and determined whether partnership characteristics, contraceptive behaviors and pregnancy intentions mediated the relationship between gang membership and pregnancy. Pregnancy incidence was determined by urine-based testing and self-report. Seventy-seven percent of participants were Latinas, with one in five born outside the U.S. One-quarter (27.4%) became pregnant over follow-up. Participants’ gang membership had no significant effect on pregnancy incidence (Hazard Ratio (HR)=1.25; 95% confidence interval (CI): 0.54, 3.45); however, having partners who were in gangs was associated with pregnancy (HR=1.90; 95% CI: 1.09, 3.32). Perceived male partner’s pregnancy intentions and having a partner in detention each mediated the effect of partner’s gang membership on pregnancy risk. Increased pregnancy incidence among young women with gang-involved partners highlights the importance of integrating reproductive health prevention into programs for gang-involved youth. In addition, high pregnancy rates indicate a heightened risk for sexually transmitted infections

Fabrication of metallic patterns by microstencil lithography on polymer surfaces suitable as microelectrodes in integrated microfluidic systems

Microstencil lithography, i.e. local deposition of micrometer scale patterns through small shadow masks, is a promising method for metal micropattern definition on polymer substrates that cannot be structured using organic-solvent-based photoresist technology. We propose to apply microstencil lithography to fabricate microelectrodes on flat and 3D polymer substrates, such as PMMA or SU-8, which form parts of microfluidic systems with integrated microelectrodes. Microstencil lithography is accompanied by two main issues when considered for application as a low-cost, reproducible alternative to standard photolithography on polymer substrates. In this paper we assess in detail (i) the reduction of aperture size (clogging) after several metal evaporation steps and corresponding change of deposited pattern size and (ii) loss in the resolution (blurring) of the deposited microstructures when there is a several micrometers large gap between the stencil membrane and the substrate. The clogging of stencil apertures induced by titanium and copper evaporation was checked after each evaporation step, and it was determined that approximately 50% of the thickness of the evaporated metals was deposited on the side walls of the stencil apertures. The influence of a gap on the deposited structures was analyzed by using 18 um thick SU-8 spacers placed between the microstencil and the substrate. The presence of an 18 um gapmade the deposited structures notably blurred. The blurring mechanism of deposited structures is discussed based on a simplified geometrical model. The results obtained in this paper allow assessing the feasibility of using stencil-based lithography for unconventional surface patterning, which shows the limits of the proposed method, but also provides a guideline on a possible implementation for combined polymer-electrode microsystems, where standard photoresist technology fails

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae