Differential lipid dependence of function of bacterial sodium channel homologues

The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in maintaining the hydrophobic/charged interactions necessary for structure, conformational flexibility and function. Despite the intimate relationship between ion channels and the membranes in which they are embedded, challenges resulting from the dynamic and complex nature of cellular membranes have limited our ability to address the functional role of these interactions. To directly assess lipid dependence of activity, we examined channel function ofthree purified bacterial sodium channel orthologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3:1 ratio of POPE and another glycerophospholipid (POPC, POPG, POPS, Cardiolipin (CL), POPA, or PI). We observed a unique lipid dependence for each homologue tested. Common to each was a low level of activity above background (uptake into protein free liposomes) when the second lipid was a zwitterionic lipid such as POPE and POPC. Maximal activity for full-length NaChBac and NavMs proteins was observed in POPE + POPG liposomes. On the other hand, full-length NavSp channels possessed a different lipid dependence, with maximal activity in liposomes containing POPE + PI. No strong lipid dependence was observed for pore-only constructs of NavMs or NavSp, that lacked the S1-S4 segments, suggesting that the lipid dependence of sodium channels may arise from their abilities to affect the voltage-sensing domains. The effect may be maximized by specific lipid-protein interactions that are uniquely favourable in each homologue, giving rise to differing lipid dependences

Development of X-43A Mach 10 Leading Edges

The nose leading edge of the Hyper-X Mach 10 vehicle was orginally anticipated to reach temperatures near 4000 F at the leading-edge stagnation line. A SiC coated carbon/carbon (C/C) leading-edge material will not survive that extreme temperature for even a short duration single flight. To identify a suitable leading edge for the Mach 10 vehicle, arc-jet testing was performed on thirteen leading-edge segments fabricated from different material systems to evaluate their performance in a simulated flight environment. Hf, Zr, Si, and Ir based materials, in most cases as a coating on C/C, were included in the evaluation. Afterwards, MER, Tucson, AZ was selected as the supplier of the flight vehicle leading edges. The nose and the vertical and horizontal tail leading edges were fabricated out of a 3:1 biased high thermal conductivity C/C. The leading edges were coated with a three layer coating comprised of a SiC conversion of the top surface of the C/C, followed by a chemical vapor deposited layer of SiC, followed by a thin chemical vapor deposited layer of HfC. This paper will describe the fabrication of the Mach 10 C/C leading edges and the testing performed to validate performance

Small-Scale Fisheries Bycatch Jeopardizes Endangered Pacific Loggerhead Turtles

Background. Although bycatch of industrial-scale fisheries can cause declines in migratory megafauna including seabirds, marine mammals, and sea turtles, the impacts of small-scale fisheries have been largely overlooked. Small-scale fisheries occur in coastal waters worldwide, employing over 99 % of the world’s 51 million fishers. New telemetry data reveal that migratory megafauna frequent coastal habitats well within the range of small-scale fisheries, potentially producing high bycatch. These fisheries occur primarily in developing nations, and their documentation and management are limited or non-existent, precluding evaluation of their impacts on non-target megafauna. Principal Findings/Methodology. 30 North Pacific loggerhead turtles that we satellite-tracked from 1996–2005 ranged oceanwide, but juveniles spent 70 % of their time at a high use area coincident with small-scale fisheries in Baja California Sur, Mexico (BCS). We assessed loggerhead bycatch mortality in this area by partnering with local fishers to 1) observe two small-scale fleets that operated closest to the high use area and 2) through shoreline surveys for discarded carcasses. Minimum annual bycatch mortality in just these two fleets at the high use area exceeded 1000 loggerheads year 21, rivaling that of oceanwide industrial-scale fisheries, and threatening the persistence of this critically endangered population. As a result of fisher participation in this study and a bycatch awareness campaign, a consortium of local fishers and other citizens are working to eliminate their bycatch and to establish a national loggerhea

Seasonality and the effects of weather on Campylobacter infections

Background Campylobacteriosis is a major public health concern. The weather factors that influence spatial and seasonal distributions are not fully understood. Methods To investigate the impacts of temperature and rainfall on Campylobacter infections in England and Wales, cases of Campylobacter were linked to local temperature and rainfall at laboratory postcodes in the 30 days before the specimen date. Methods for investigation included a comparative conditional incidence, wavelet, clustering, and time series analyses. Results The increase of Campylobacter infections in the late spring was significantly linked to temperature two weeks before, with an increase in conditional incidence of 0.175 cases per 100,000 per week for weeks 17 to 24; the relationship to temperature was not linear. Generalized structural time series model revealed that changes in temperature accounted for 33.3% of the expected cases of Campylobacteriosis, with an indication of the direction and relevant temperature range. Wavelet analysis showed a strong annual cycle with additional harmonics at four and six months. Cluster analysis showed three clusters of seasonality with geographic similarities representing metropolitan, rural, and other areas. Conclusions The association of Campylobacteriosis with temperature is likely to be indirect. High-resolution spatial temporal linkage of weather parameters and cases is important in improving weather associations with infectious diseases. The primary driver of Campylobacter incidence remains to be determined; other avenues, such as insect contamination of chicken flocks through poor biosecurity should be explored

The culture variable vis-à-vis anti-bribery law: a grey area in transnational corporate criminal liability

Cross-border transactions are generating corresponding globalisation of law enforcement efforts. Culture has significantly influenced the legal analysis of anti-bribery law. With the increase of transnational bribery, benefits from globalisation will be undermined unless an effective legal regime can mitigate the harm of bribery. It is perceived that corruption in China is more prevalent than in the West given its embedded place in Chinese culture. It is further alleged that Chinese multinational companies (MNCs) are taking advantage of an unlevel playing field, as they are not subject to stringently-enforced anti-bribery laws. This hypothesis creates a myriad of anti-bribery problems in terms of legislation and enforcement, which particularly manifest in China’s perceived cultural toleration of bribery. Cultural assumptions undermine the global anti-bribery regime and compromise potential collaborative anti-bribery efforts across jurisdictions in a rapidly globalizing world. The Chinese culture does not necessarily impede China’s criminalisation of paying bribes to foreign officials. It is argued that the cultural role should not be overestimated, otherwise the hazard of the ethnocentric engagement with the Chinese culture would affect the ability of foreign MNCs to integrate their global compliance programmes. Multinationals can only mitigate their exposure to criminal liability globally, provided that they comply robustly with anti-bribery laws of both home and host jurisdictions

The Making of a Productivity Hotspot in the Coastal Ocean

Highly productive hotspots in the ocean often occur where complex physical forcing mechanisms lead to aggregation of primary and secondary producers. Understanding how hotspots persist, however, requires combining knowledge of the spatio-temporal linkages between geomorphology, physical forcing, and biological responses with the physiological requirements and movement of top predators.) off the Baja California peninsula, Mexico.We have identified the set of conditions that lead to a persistent top predator hotspot, which increases our understanding of how highly migratory species exploit productive regions of the ocean. These results will aid in the development of spatially and environmentally explicit management strategies for marine species of conservation concern

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies

Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Objective: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results: Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions: We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation