The meiosis-specific Cdc20 family-member Ama1 promotes binding of the Ssp2 activator to the Smk1 MAP kinase.

Smk1 is a meiosis-specific MAP kinase (MAPK) in budding yeast that is required for spore formation. It is localized to prospore membranes (PSMs), the structures that engulf haploid cells during meiosis II (MII). Similar to canonically activated MAPKs, Smk1 is controlled by phosphorylation of its activation-loop threonine (T) and tyrosine (Y). However, activation loop phosphorylation occurs via a noncanonical two-step mechanism in which 1) the cyclin-dependent kinase activating kinase Cak1 phosphorylaytes T207 during MI, and 2) Smk1 autophosphorylates Y209 as MII draws to a close. Autophosphorylation of Y209 and catalytic activity for substrates require Ssp2, a meiosis-specific protein that is translationally repressed until anaphase of MII. Ama1 is a meiosis-specific targeting subunit of the anaphase-promoting complex/cyclosome that regulates multiple steps in meiotic development, including exit from MII. Here, we show that Ama1 activates autophosphorylation of Smk1 on Y209 by promoting formation of the Ssp2/Smk1 complex at PSMs. These findings link meiotic exit to Smk1 activation and spore wall assembly

Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies

BACKGROUND: <br/> Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.<br/> METHODOLOGY:<br/> Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.<br/> PRINCIPLE FINDINGS:<br/> IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.<br/> CONCLUSION:<br/> Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh

Electrically induced drop detachment and ejection

A deformed droplet may leap from a solid substrate, impelled to detach through the conversion of surface energy into kinetic energy that arises as it relaxes to a sphere. Electrowetting provides a means of preparing a droplet on a substrate for lift-off. When a voltage is applied between a water droplet and a dielectric-coated electrode, the wettability of the substrate increases in a controlled way, leading to the spreading of the droplet. Once the voltage is released, the droplet recoils, due to a sudden excess in surface energy, and droplet detachment may follow. The process of drop detachment and lift-off, prevalent in both biology and micro-engineering, has to date been considered primarily in terms of qualitative scaling arguments for idealized superhydrophobic substrates. We here consider the eletrically-induced ejection of droplets from substrates of finite wettability and analyze the process quantitatively. We compare experiments to numerical simulations and analyze how the energy conversion efficiency is affected by the applied voltage and the intrinsic contact angle of the droplet on the substrate. Our results indicate that the finite wettability of the substrate significantly affects the detachment dynamics, and so provide new rationale for the previously reported large critical radius for drop ejection from micro-textured substrates

Electrowetting-on-Dielectric Actuation of a Vertical Translation and Angular Manipulation Stage

Adhesion and friction during physical contact of solid components in microelectromechanical systems (MEMS) often lead to device failure. Translational stages that are fabricated with traditional silicon MEMS typically face these tribological concerns. This work addresses these concerns by developing a MEMS vertical translation, or focusing, stage that uses electrowetting-on-dielectric (EWOD) as the actuating mechanism. EWOD has the potential to eliminate solid-solid contact by actuating through deformation of liquid droplets placed between the stage and base to achieve stage displacement. Our EWOD stage is capable of linear spatial manipulation with resolution of 10 μm over a maximum range of 130 μm and angular deflection of approximately ±1°, comparable to piezoelectric actuators. We also developed a model that suggests a higher intrinsic contact angle on the EWOD surface can further improve the translational range, which was validated experimentally by comparing different surface coatings. The capability to operate the stage without solid-solid contact offers potential improvements for applications in micro-optics, actuators, and other MEMS devices.United States. Office of Naval ResearchNational Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)National Science Foundation (U.S.) (Major Research Instrumentation Grant for Rapid Response Research (MRI-RAPID)

Investigation into cardiac sympathetic innervation during the commencement of haemodialysis in patients with chronic kidney disease

Background: Patients with chronic kidney disease (CKD) who undergo chronic haemodialysis (HD) show altered sympathetic tone, which is related to a higher cardiovascular mortality. The purpose of this study was to investigate the effect of transition from pre-HD to HD on cardiac sympathetic innervation. Methods: Eighteen patients aged 58 ± 18 years (mean ± standard deviation [SD]), 13 males and five females, with stage 5 CKD and nine healthy control subjects aged 52 ± 17 (mean ± SD), three males and six females, were included in this prospective study between May 2010 and December 2013. All patients underwent 123I-labelled meta-iodobenzylguanidine (123I-MIBG) scintigraphy for cardiac sympathetic innervation and electrocardiographically gated adenosine stress and rest 99mTc-labelled tetrofosmin single-photon emission computed tomography for myocardial perfusion imaging prior to (pre-HD) and 6 months after the start of HD. Results of 123I-MIBG scans in patients were compared to controls. Impaired cardiac sympathetic innervation was defined as late heart-to-mediastinum ratio (HMR) < 2.0. Results: Mean late HMR was lower in patients during HD (2.3) than in controls (2.9) (p = 0.035); however, in patients it did not differ between pre-HD and after the start of HD. During HD, two patients showed new sympathetic innervation abnormalities, and in three patients innervation abnormalities seemed to coincide with myocardial perfusion abnormalities. Conclusions: CKD patients show cardiac sympathetic innervation abnormalities, which do not seem to progress during the maintenance HD. The relationship between sympathetic innervation abnormalities and myocardial perfusion abnormalities in HD patients needs further exploration

Optimización de la hemoglobina preoperatoria en cirugía ortopédica mayor utilizando hierro intravenoso con o sin eritropoyetina. Estudio epidemiológico

Objetivo: Evaluar la efectividad del tratamiento con hierro intravenoso, solo o asociado a eritropoyetina (rHuEPO), mediante el incremento de hemoglobina (Hb). Como objetivo secundario se analizó la relación del incremento de Hb con los parámetros utilizados para evaluar la anemia. Material y método: Estudio observacional retrospectivo realizado en 2 centros entre enero de 2005 y diciembre de 2009. Se incluyeron pacientes sometidos a cirugía ortopédica electiva con déficit de hierro y que fueron tratados con hierro sacarosa intravenosos solo o asociado a rHuEPO. Se analizó la efectividad del tratamiento mediante la diferencia entre la Hb basal y la Hb previa a la cirugía y se valoró la relación entre los parámetros hematimétricos y del metabolismo del hierro con la efectividad del tratamiento. Resultados: Se incluyeron 412 pacientes que recibieron una mediana de 800mg de hierro sacarosa. A 125 pacientes (30,4%) se les asoció 2,4 viales de rHuEPO. El incremento de Hb fue de 0,8 (1,1) g/dL en los pacientes tratados con hierro intravenoso y de 1,5 (1,3) g/dL en los que se asoció rHuEPO (p<0,01). El incremento de Hb en los pacientes tratados con hierro se correlacionó con el porcentaje de hematíes hipocromos (r=0,52) y el valor del receptor soluble de la transferrina (r=0,59). Conclusiones: La efectividad del tratamiento con hierro sacarosa en pacientes con déficit de hierro para la optimización de la Hb preoperatoria fue moderada, siendo mayor con la administración adyuvante de eritropoyetina. La determinación de los parámetros funcionales del estado del hierro nos podría guiar para mejorar la efectividad del tratamiento

Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis.

INTRODUCTION: Quantifying excess cause-specific mortality among people with coeliac disease (CD) compared with the general population accounting for competing risks will allow accurate information to be given on risk of death from specific causes. METHOD: We identified from the Clinical Practice Research Datalink all patients with CD linked to Office for National Statistics between 1998 and 2012. We selected controls by frequency matching from the registered general practice population within 10-year age bands. We calculated the adjusted cumulative incidence (including adjustment for competing risks) and excess cumulative incidence for different causes of death up to 10 years from diagnosis. RESULTS: Of the 10 825 patients with CD, 773 died within the study period. The overall mortality rate among patients with CD was 128/10 000 person years compared with 153/10 000 in controls (HR=0.94 95% CI 0.84 to 1.01). We found no overall difference in the cumulative incidence of respiratory disease, digestive disease or cancer related death among cases and controls. The adjusted cumulative incidence of death from cardiovascular deaths was slightly lower compared with those without CD diagnosis (CD 0.32% vs controls 0.41%) with a corresponding excess cumulative incidence of -0.08% (95% CI -0.13 to -0.04). However, patients with CD had 0.15% excess risk (95% CI 0.03 to 0.27) of deaths from non-Hodgkin's lymphoma from the general population baseline risk. CONCLUSIONS: Overall, people with CD have no major excess risk of cancer, digestive disease or respiratory disease related or cardiovascular mortality compared with the general population. These findings should be reassuring to patients with CD and clinicians managing their care

Attribution and contestation: Relations between elites and other social groups

In this article we explore the often ambiguous relations between elites and other social groups, both subordinate and of relatively equal standing. The article draws on two distinctive ethnographic cases: the white Franco-Mauritian elite, and the expert elite of management consultants in a Western European context. Our analysis of the two cases provides insights into how the power and status of elites is both contested and attributed by the people they interact with and relate to in concrete, yet substantially different contexts and situations. The aim is to show how the position and power of different kinds of elites is relationally negotiated and achieved. As we argue, a better understanding of the role of other social groups in the attribution, maintenance and contestation of status is relevant for understanding both more traditional economic elites and expert elites without tight networks

Exploring host and pathogen biomarkers for leprosy

Leprosy is a multifactorial chronic disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that affects the skin and nerves. More than 200.000 new cases are diagnosed per year; thus, transmission is still ongoing. The most likely way of transmission is the respiratory route form human-to-human; however, transmission is still not clearly understood. Early diagnosis of leprosy is crucial to reduce and avoid transmission as well as leprosy-associated disabilities, which are also a cause of stigma. Currently, diagnosis is performed based on clinical signs and symptoms and late- or mis-diagnosis are not uncommon.In this thesis, we combined the study of pathogen transmission with host transcriptomic and genomic biomarkers. To explore M. leprae transmission a One Health approach was followed, where human, animal and environmental samples were studied.The combination of demographic characteristics, pathogen detection, genetic and/or transcriptomic biomarkers can be applied in a multifactorial leprosy signature applicable for early diagnosis of leprosy and/or to guide intervention strategies. Identification of predictive biomarkers will in due course lead to prompt treatment, preventing leprosy-associated irreversible disabilities as well as reducing M. leprae transmission.Q.M. Gastmann-Wichers Foundation, R2STOP research grant from effect:hope together with the Mission to End Leprosy, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Netherlands Leprosy Relief Foundation and the Leprosy Research Initiative, both together with the Turing Foundation.LUMC / Geneeskund

Soil Porosity Conditions in Flood-Prone Areas of the Prosperous Swamp of Bengkulu City Based on Geoelectrical Measurement

Surface porosity conditions in part of flood-prone areas at Rawa Makmur Village have been mapped from the surface to a depth of 30 meters. The aims of this research are to identify the infiltration of soil which is described by variations in resistivity and rock porosity values. It is obtained from the 1D geoelectric method using Vertical Electrical Sounding and as many as 10 measurement points. According to analysis, it is explained that Rawa Makmur area has low porosity and resistivity values. The porosity conditions in the observation point area were in very bad conditions. The infiltration process is very slow, causing the accumulation of a large amount of water mass and a fairly high pool of water.&nbsp; It also showed that the water flowing in this area was difficult to infiltrate, so it caused the Rawa Makmur area to become flooded when it rained