SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase

Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion results in enhanced vacuole integrity and intracellular growth of a sdhA mutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA alters OCRL function, enlarging endosomes, driving endosomal accumulation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), and interfering with endosomal trafficking. SdhA interrupts Rab guanosine triphosphatase (GTPase)-OCRL interactions by binding to the OCRL ASPM-SPD2-Hydin (ASH) domain, without directly altering OCRL 5-phosphatase activity. The Legionella vacuole encompassing the sdhA mutant accumulates OCRL and endosomal antigen EEA1 (Early Endosome Antigen 1), consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole.Peer Reviewe

Developing an e-infrastructure for social science

We outline the aims and progress to date of the National Centre for e-Social Science e-Infrastructure project. We examine the challenges faced by the project, namely in ensuring outputs are appropriate to social scientists, managing the transition from research projects to service and embedding software and data within a wider infrastructural framework. We also provide pointers to related work where issues which have ramifications for this and similar initiatives are being addressed

Pit latrine fecal sludge resistance using a dynamic cone penetrometer in low income areas in Mzuzu city, Malawi

Pit latrines can provide improved household sanitation, but without effective and inexpensive emptying options, they are often abandoned once full and may pose a public health threat. Emptying techniques can be difficult, as the sludge contents of each pit latrine are different. The design of effective emptying techniques (e.g., pumps) is limited by a lack of data characterizing typical in situ latrine sludge resistance. This investigation aimed to better understand the community education and technical engineering needs necessary to improve pit latrine management. In low income areas within Mzuzu city, Malawi, 300 pit latrines from three distinct areas were assessed using a dynamic cone penetrometer to quantify fecal sludge strength, and household members were surveyed to determine their knowledge of desludging procedures and practices likely to impact fecal sludge characteristics. The results demonstrate that there is a significant difference in sludge strength between lined and unlined pits within a defined area, though sludge hardened with depth, regardless of the pit type or region. There was only limited association between cone penetration depth and household survey data. To promote the adoption of pit emptying, it is recommended that households be provided with information that supports pit emptying, such as latrine construction designs, local pit emptying options, and cost. This study indicates that the use of a penetrometer test in the field prior to pit latrine emptying may facilitate the selection of appropriate pit emptying technology

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

Exploring Pompeii: discovering hospitality through research synergy

Hospitality research continues to broaden through an ever-increasing dialogue and alignment with a greater number of academic disciplines. This paper demonstrates how an enhanced understanding of hospitality can be achieved through synergy between archaeology, the classics and sociology. It focuses on classical Roman life, in particular Pompeii, to illustrate the potential for research synergy and collaboration, to advance the debate on hospitality research and to encourage divergence in research approaches. It demonstrates evidence of commercial hospitality activities through the excavation hotels, bars and taverns, restaurants and fast food sites. The paper also provides an example of the benefits to be gained from multidisciplinary analysis of hospitality and tourism

Comparison of blind, ultrasound- and neurostimulator-guided methods of percutaneous inferior alveolar nerve block

Background: An inferior alveolar nerve block is often utilised for anaesthesia of the mandibular arcade of teeth prior to dental procedures. It has been described with multiple approaches and methods; however, at the current time, no direct comparison of percutaneous methods is available. Objectives: To compare the accuracy of percutaneous infiltration of the inferior alveolar nerve with a ventral blind approach (control) to blind caudal approach, ultrasound-guided and neurostimulator-guided methods. Study design: Prospective comparison of methods using anaesthetised horses prior to euthanasia or cadavers, being utilised for another study. Methods: An 18 G spinal needle was used to inject a volume of 1 ml, composed of 0.5 ml of methylene blue and 0.5 ml of iodinated CT contrast medium, with placement guided by the aforementioned methods. Following injection the needle was left in place, CT-imaging was performed and then the skulls were dissected. CT enabled assessment of the coverage of the mandibular foramen with contrast medium and distance of the needle tip from the mandibular foramen and dissection enabled assessment of the staining of the inferior alveolar nerve and lingual nerve. Results: The highest percentage of contrast staining of the inferior alveolar nerve and coverage of the mandibular foramen at CT was achieved with caudal blind and ultrasound-guided approaches; however, no group reached a significant difference to control (ventral blind approach). Concurrent staining of the lingual nerve (possibly associated with undesired side effects) had high incidence and was similar between groups. Main limitations: Use of horses under anaesthesia/cadavers does not replicate clinical conditions and staining/coverage is assumed to relate to a clinically effective block. Conclusions: Ultrasound-guided and caudal approaches did have increased percentage of successful staining, but neither reached significance compared to the ventral blind approach

Coulomb singularities in scattering wave functions of spin-orbit-coupled states

We report on our analysis of the Coulomb singularity problem in the frame of the coupled channel scattering theory including spin-orbit interaction. We assume that the coupling between the partial wave components involves orbital angular momenta such that $\Delta l = 0, \pm 2$. In these conditions, the two radial functions, components of a partial wave associated to two values of the angular momentum $l$, satisfy a system of two second-order ordinary differential equations. We examine the difficulties arising in the analysis of the behavior of the regular solutions near the origin because of this coupling. First, we demonstrate that for a singularity of the first kind in the potential, one of the solutions is not amenable to a power series expansion. The use of the Lippmann-Schwinger equations confirms this fact: a logarithmic divergence arises at the second iteration. To overcome this difficulty, we introduce two auxilliary functions which, together with the two radial functions, satisfy a system of four first-order differential equations. The reduction of the order of the differential system enables us to use a matrix-based approach, which generalizes the standard Frobenius method. We illustrate our analysis with numerical calculations of coupled scattering wave functions in a solid-state system

Thermal Analysis of Potted Litz Wire for High-Power-Density Aerospace Electric Machines

Increasing the power density and efficiency of electric machines (motors and generators) is integral to bringing Electrified Aircraft (EA) to commercial realization. To that end an effort to create a High Efficiency Megawatt Motor (HEMM) with a goal of exceeding 98% efficiency and 1.46 MW of power has been undertaken at the NASA Glenn Research Center. Of the motor components the resistive losses in the stator windings are by far the largest contributor (34%) to total motor loss. The challenge is the linear relationship between resistivity and temperature, making machine operation sensitive to temperature increases. In order to accurately predict the thermal behavior of the stator the thermal conductivity of the Litz wire-potting-electrical insulation system must be known. Unfortunately, this multi material system has a wide range of thermal conductivities (0.1 W/m-K 400 W/m-K) and a high anisotropy (axial vs transverse) making the prediction of the transverse thermal conductivity an in turn the hot spot temperatures in the windings is difficult. In order to do this a device that simulates the thermal environment found in the HEMM stator was designed. This device is not unlike the motorettes (little motors) that are described in IEEE standards for testing electrical insulation lifetimes or other electric motor testing. However, because the HEMM motor design includes significant rotor electrical and thermal considerations the term motorette was not deemed appropriate. Instead statorette (or little stator) was adopted as the term for this test device. This paper discussed the design, thermal heat conjugate analysis (thermal model), manufacturing and testing of HEMM's statorette. Analysis of the results is done by thermal resistance network model and micro thermal model and is compared to analytical predictions of thermal conductivity of the insulated and potted Litz wire system

Comparing biological markers of Alzheimer\u27s disease across blood fraction and platforms: Comparing apples to oranges

Introduction: This study investigated the comparability of potential Alzheimer\u27s disease (AD) biomarkers across blood fractions and assay platforms. Methods: Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots. Results: On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared \u3e50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty acid-binding protein (FABP) R2 = 0.94, I309 R2 = 0.94, IL-5 R2 = 0.94, IL-6 R2 = 0.94, eotaxin3 R2 = 0.91, IL-18 R2 = 0.87, soluble tumor necrosis factor receptor 1 R2 = 0.85, and pancreatic polypeptide R2 = 0.81). When examining protein concentrations across platforms, only five markers shared \u3e50% of the variance (beta 2 microglobulin R2 = 0.92, IL-18 R2 = 0.80, factor VII R2 = 0.78, CRP R2 = 0.74, and FABP R2 = 0.70). Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers

The impact of regionalized trauma care on the distribution of severely injured patients in the Netherlands

BACKGROUND: Twenty years ago, an inclusive trauma system was implemented in the Netherlands. The goal of this study was to evaluate the impact of structured trauma care on the concentration of severely injured patients over time. METHODS: All severely injured patients (Injury Severity Score [ISS] ≥ 16) documented in the Dutch Trauma Registry (DTR) in the calendar period 2008–2018 were included for analysis. We compared severely injured patients, with and without severe neurotrauma, directly brought to trauma centers (TC) and non-trauma centers (NTC). The proportion of patients being directly transported to a trauma center was determined, as was the total Abbreviated Injury Score (AIS), and ISS. RESULTS: The documented number of severely injured patients increased from 2350 in 2008 to 4694 in 2018. During this period, on average, 70% of these patients were directly admitted to a TC (range 63–74%). Patients without severe neurotrauma had a lower chance of being brought to a TC compared to those with severe neurotrauma. Patients directly presented to a TC were more severely injured, reflected by a higher total AIS and ISS, than those directly transported to a NTC. CONCLUSION: Since the introduction of a well-organized trauma system in the Netherlands, trauma care has become progressively centralized, with more severely injured patients being directly presented to a TC. However, still 30% of these patients is initially brought to a NTC. Future research should focus on improving pre-hospital triage to facilitate swift transfer of the right patient to the right hospital