Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome

Protein synthesis is catalyzed in the peptidyl transferase center (PTC), located in the large (50S) subunit of the ribosome. No high-resolution structure of the intact ribosome has contained a complete active site including both A- and P-site tRNAs. In addition, although past structures of the 50S subunit have found no ordered proteins at the PTC, biochemical evidence suggests that specific proteins are capable of interacting with the 3′ ends of tRNA ligands. Here we present structures, at 3.6-Å and 3.5-Å resolution respectively, of the 70S ribosome in complex with A- and P-site tRNAs that mimic pre- and post-peptidyl-transfer states. These structures demonstrate that the PTC is very similar between the 50S subunit and the intact ribosome. They also reveal interactions between the ribosomal proteins L16 and L27 and the tRNA substrates, helping to elucidate the role of these proteins in peptidyl transfer

Retinal microvascular parameters are not associated with reduced renal function in a study of individuals with type 2 diabetes

Abstract The eye provides an opportunistic “window” to view the microcirculation. There is published evidence of an association between retinal microvascular calibre and renal function measured by estimated glomerular filtration rate (eGFR) in individuals with diabetes mellitus. Beyond vascular calibre, few studies have considered other microvascular geometrical features. Here we report novel null findings for measures of vascular spread (vessel fractal dimension), tortuosity, and branching patterns and their relationship with renal function in type 2 diabetes over a mean of 3 years. We performed a nested case-control comparison of multiple retinal vascular parameters between individuals with type 2 diabetes and stable (non-progressors) versus declining (progressors) eGFR across two time points within a subset of 1072 participants from the GoDARTS study cohort. Retinal microvascular were measured using VAMPIRE 3.1 software. In unadjusted analyses and following adjustment for age, gender, systolic blood pressure, HbA1C, and diabetic retinopathy, no associations between baseline retinal vascular parameters and risk of eGFR progression were observed. Cross-sectional analysis of follow-up data showed a significant association between retinal arteriolar diameter and eGFR, but this was not maintained following adjustment. These findings are consistent with a lack of predictive capacity for progressive loss of renal function in type 2 diabetes

The elusive Heisenberg limit in quantum enhanced metrology

We provide efficient and intuitive tools for deriving bounds on achievable precision in quantum enhanced metrology based on the geometry of quantum channels and semi-definite programming. We show that when decoherence is taken into account, the maximal possible quantum enhancement amounts generically to a constant factor rather than quadratic improvement. We apply these tools to derive bounds for models of decoherence relevant for metrological applications including: dephasing,depolarization, spontaneous emission and photon loss.Comment: 10 pages, 4 figures, presentation imporved, implementation of the semi-definite program finding the precision bounds adde

Incidence and Tracking of Escherichia coli O157:H7 in a Major Produce Production Region in California

Fresh vegetables have become associated with outbreaks caused by Escherichia coli O157:H7 (EcO157). Between 1995–2006, 22 produce outbreaks were documented in the United States, with nearly half traced to lettuce or spinach grown in California. Outbreaks between 2002 and 2006 induced investigations of possible sources of pre-harvest contamination on implicated farms in the Salinas and San Juan valleys of California, and a survey of the Salinas watershed. EcO157 was isolated at least once from 15 of 22 different watershed sites over a 19 month period. The incidence of EcO157 increased significantly when heavy rain caused an increased flow rate in the rivers. Approximately 1000 EcO157 isolates obtained from cultures of>100 individual samples were typed using Multi-Locus Variable-number-tandem-repeat Analysis (MLVA) to assist in identifying potential fate and transport of EcO157 in this region. A subset of these environmental isolates were typed by Pulse Field Gel Electrophoresis (PFGE) in order to make comparisons with human clinical isolates associated with outbreak and sporadic illness. Recurrence of identical and closely related EcO157 strains from specific locations in the Salinas and San Juan valleys suggests that transport of the pathogen is usually restricted. In a preliminary study, EcO157 was detected in water at multiple locations in a low-flow creek only within 135 meters of a point source. However, possible transport up to 32 km was detected during periods of higher water flow associated with flooding. During the 2006 baby spinach outbreak investigation, transport was also detected where water was unlikely to be involved. These results indicate that contamination of the environment is a dynamic process involving multiple sources and methods of transport. Intensive studies of the sources, incidence, fate and transport of EcO157 near produce production are required to determine the mechanisms of pre-harvest contamination and potential risks for human illness

Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990-2010: A Systematic Review of Epidemiological Studies

The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner

Potential Explosive Device on a Commuter Train: What Drives Train Drivers to Deviate from the Security Procedure?

Explosives pose a major threat to urban metro rail systems. Train drivers are therefore expected to regularly perform security procedures in response to reports of suspicious items on the train. This study was conducted to develop a multi-factorial account of deviation from one such security procedure by train drivers. By analysing data from focus group interviews with 30 train drivers, observation in a rail simulator, actual cab rides, and training material four major themes emerged to explain why drivers may deliberately deviate from following normative procedures designed by their managers. This included perceived pressure from safety and service goals, stress and fatigue during peak hours of operation, and workload created by security tasks. The results are organised in a succinct model that draws a link between drivers’ perceived pressure from multiple goals, and the changing driving conditions in which they perform. The study proposes ways for managers of urban commuter rail networks to understand the pressures that their drivers face in performing security tasks that are not part of their conventional job profile. The findings can inform changes in training methods, encourage drivers to discuss their reasons for deliberate rule violation, and support the design of security procedures more likely to be implemented