Demonstration of a Multistep Mechanism for Assembly of the SRP·SRP Receptor Complex: Implications for the Catalytic Role of SRP RNA

Two GTPases in the signal recognition particle (SRP) and its receptor (SR) control the delivery of newly synthesized proteins to the endoplasmic reticulum or plasma membrane. During the protein targeting reaction, the 4.5S SRP RNA accelerates the association between the two GTPases by 400-fold. Using fluorescence resonance energy transfer, we demonstrate here that formation of a stable SRP·SR complex involves two distinct steps: a fast initial association between SRP and SR to form a GTP-independent early complex and then a GTP-dependent conformational rearrangement to form the stable final complex. We also found that the 4.5S SRP RNA significantly stabilizes the early GTP-independent intermediate. Furthermore, mutational analyses show that there is a strong correlation between the ability of the mutant SRP RNAs to stabilize the early intermediate and their ability to accelerate SRP·SR complex formation. We propose that the SRP RNA, by stabilizing the early intermediate, can give this transient intermediate a longer life time and therefore a higher probability to rearrange to the stable final complex. This provides a coherent model that explains how the 4.5S RNA exerts its catalytic role in SRP·SR complex assembly

Measuring depression severity in global mental health: comparing the PHQ-9 and the BDI-II

Grant information: This research was funded by a Wellcome Trust Senior Research Fellowship grant to VP [091834]. BW is supported through an Intermediate Research Fellowship from the Wellcome Trust/India Alliance [502680]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Pressure-induced phonon frequency shifts in transition-metal nitrides

We report the first experiments on the high pressure phonon spectra of transition-metal nitrides HfN, ZrN, and NbN, obtained by Raman scattering measurements. Two pronounced bands, which are related to the acoustic part at low frequency around 200 cm$^{-1}$ and the optical part at high frequency around 550 cm$^{-1}$ of the phonon spectrum, respectively, shift to high frequency values with increasing pressure. An analysis of the results allows us to reproduce the experimental pressure dependence of the superconducting transition temperature $T_{c}$ of ZrN and NbN.Comment: 19 pages and 6 figure

Climatology and Change of Extreme Precipitation Events in Taiwan Based on Weather Types

Taiwan\u27s most significant natural hazards are caused by hydrological extremes resulting from excessive precipitation. The threat of extreme precipitation is posed by several different types of weather patterns that affect Taiwan. This study examined the bi‐decadal changes in rainfall by defining an extreme precipitation occurrence (EPO) for a range of event durations from 1 to 24 hr. Three major weather types affecting EPO in Taiwan were identified from 1993 to 2015: the front type consisting of either a frontal zone or convective systems developing with an apparent Meiyu cloudband, diurnal rainfall events when no apparent synoptic features are present, and a tropical cyclone (TC) type according to the maximum sustained wind radius of a TC. Results show that TC‐type events have the greatest overall contribution to EPO at longer (\u3e6 hr) durations. Diurnal/afternoon convection events contribute most to the shorter (\u3c3 hr) duration EPO, while frontal/Meiyu systems prevail in the medium (3–6 hr) duration. EPO of almost all durations have experienced an increase, with the 3‐ and 12‐hr EPO having increased by 4.6 days each over the 23 years. However, apparent decadal‐scale variability exists in these EPO associated with the decreasing tendency of EPO after the mid‐2000s, particularly the longer duration (\u3e6 hr) EPO associated with the TC‐type events in summer. The distinction between EPO trends for the entire island of Taiwan and for the Taipei metropolitan area alone (northern Taiwan, population of 7 million) were compared, and an intriguing interannual variation is reported in the TC‐type EPO associated with the TC season 1 year to a year and half just before an El Niño–Southern Oscillation event. The analysis here provides refined statistical distributions of extreme rainfall, and these can contribute to the revision of governmental definitions for weather disasters that are used in mitigation and response strategies

The performance of local authority sports facilities in England during a period of recession and austerity

This paper examines how public sport facilities in England, which are dependent on subsidy from local authorities, have performed during a period of recession and austerity. Using data derived from Sport England's National Benchmarking Service (NBS), we track the changes in a series of key operational performance measures to investigate how local authority sports centres have fared between 2005/06 and 2015/16. Four dimensions of performance are analysed, namely: access; finance; utilisation; and, customer satisfaction. The study includes 1,116 sports centres in the time frame under review. Our results show that the overall financial efficiency of English public sport facilities has improved significantly in the face of a reduction in local authority expenditure on sport and leisure services. There appears to be a business model in the sector that includes outsourcing management and raising activity charges, which has been accompanied by higher levels of customer satisfaction with price-related service attributes and with the overall experience of using a facility. A possible explanation for these findings might be an improved quality of provision and greater customer orientation. At the same time, there appears to be a diminished focus on social inclusion objectives. We therefore conclude that promoting access to public sport facilities for hard-to-reach or disadvantaged groups has been compromised in exchange for the pursuit of financial stability. A key challenge is how to achieve market development whereby new and targeted customers are attracted to these existing facilities

Variable structure control with chattering reduction of a generalized T-S model

In this paper, a fuzzy logic controller (FLC) based variable structure control (VSC) is presented. The main objective is to obtain an improved performance of highly non-linear unstable systems. New functions for chattering reduction and error convergence without sacrificing invariant properties are proposed. The main feature of the proposed method is that the switching function is added as an additional fuzzy variable and will be introduced in the premise part of the fuzzy rules; together with the state variables. In this work, a tuning of the well known weighting parameters approach is proposed to optimize local and global approximation and modelling capability of the Takagi-Sugeno (T-S) fuzzy model to improve the choice of the performance index and minimize it. The main problem encountered is that the T-S identification method can not be applied when the membership functions are overlapped by pairs. This in turn restricts the application of the T-S method because this type of membership function has been widely used in control applications. The approach developed here can be considered as a generalized version of the T-S method. An inverted pendulum mounted on a cart is chosen to evaluate the robustness, effectiveness, accuracy and remarkable performance of the proposed estimation approach in comparison with the original T-S model. Simulation results indicate the potential, simplicity and generality of the estimation method and the robustness of the chattering reduction algorithm. In this paper, we prove that the proposed estimation algorithm converge the very fast, thereby making it very practical to use. The application of the proposed FLC-VSC shows that both alleviation of chattering and robust performance are achieved

Hendra Virus Outbreak with Novel Clinical Features, Australia

To determine the epidemiologic and clinical features of a 2008 outbreak of Hendra virus infection in a veterinary clinic in Australia, we investigated the equine case-series. Four of 5 infected horses died, as did 1 of 2 infected staff members. Clinical manifestation in horses was predominantly neurologic. Preclinical transmission appears likely

Redox, haem and CO in enzymatic catalysis and regulation

The present paper describes general principles of redox catalysis and redox regulation in two diverse systems. The first is microbial metabolism of CO by the Wood–Ljungdahl pathway, which involves the conversion of CO or H2/CO2 into acetyl-CoA, which then serves as a source of ATP and cell carbon. The focus is on two enzymes that make and utilize CO, CODH (carbon monoxide dehydrogenase) and ACS (acetyl-CoA synthase). In this pathway, CODH converts CO2 into CO and ACS generates acetyl-CoA in a reaction involving Ni·CO, methyl-Ni and acetyl-Ni as catalytic intermediates. A 70 Å (1 Å=0.1 nm) channel guides CO, generated at the active site of CODH, to a CO ‘cage’ near the ACS active site to sequester this reactive species and assure its rapid availability to participate in a kinetically coupled reaction with an unstable Ni(I) state that was recently trapped by photolytic, rapid kinetic and spectroscopic studies. The present paper also describes studies of two haem-regulated systems that involve a principle of metabolic regulation interlinking redox, haem and CO. Recent studies with HO2 (haem oxygenase-2), a K+ ion channel (the BK channel) and a nuclear receptor (Rev-Erb) demonstrate that this mode of regulation involves a thiol–disulfide redox switch that regulates haem binding and that gas signalling molecules (CO and NO) modulate the effect of haem.National Institutes of Health (U.S.) (NIH grant GM69857)National Institutes of Health (U.S.) (NIH grant GM39451)National Institutes of Health (U.S.) (NIH grant HL 102662)National Institutes of Health (U.S.) (NIH grant GM65440)National Institutes of Health (U.S.) (NIH grant GM48242)National Institutes of Health (U.S.) (NIH grant Y1-GM- 1104)National Institutes of Health (U.S.) (NIH grant GM065318)National Institutes of Health (U.S.) (NIH grant AG027349)National Science Foundation (U.S.) (grant number CHE-0745353)United States. Dept. of Energy. Office of Biological and Environmental ResearchHoward Hughes Medical Institute (Investigator