Ribosome recycling induces optimal translation rate at low ribosomal availability

Funding statement The authors thank BBSRC (BB/F00513/X1, BB/I020926/1 and DTG) and SULSA for funding. Acknowledgement The authors thank R. Allen, L. Ciandrini, B. Gorgoni and P. Greulich for very helpful discussions and careful reading of the manuscript.Peer reviewedPublisher PD

A three-dimensional finite element model of maximal grip loading in the human wrist

The aim of this work was to create an anatomically accurate three-dimensional finite element model of the wrist, applying subject-specific loading and quantifying the internal load transfer through the joint during maximal grip. For three subjects, representing the anatomical variation at the wrist, loading on each digit was measured during a maximal grip strength test with simultaneous motion capture. The internal metacarpophalangeal joint load was calculated using a biomechanical model. High-resolution magnetic resonance scans were acquired to quantify bone geometry. Finite element analysis was performed, with ligaments and tendons added, to calculate the internal load distribution. It was found that for the maximal grip the thumb carried the highest load, an average of 72.2 ¡ 20.1 N in the neutral position. Results from the finite element model suggested that the highest regions of stress were located at the radial aspect of the carpus. Most of the load was transmitted through the radius, 87.5 per cent, as opposed to 12.5 per cent through the ulna with the wrist in a neutral position. A fully three-dimensional finite element analysis of the wrist using subject-specific anatomy and loading conditions was performed. The study emphasizes the importance of modelling a large ensemble of subjects in order to capture the spectrum of the load transfer through the wrist due to anatomical variation

TEACHING IN A CONNECTED WORLD: NEW APPROACHES IN TEACHING BIOCHEMISTRY ADOPTED AT THE MEDICAL UNIVERSITY OF VARNA, BULGARIA

This paper aims at improving the content of the biochemistry curriculum and the methods by which it was delivered at the Medical University of Varna in terms of course content, examination standards and obtaining a feedback from the students. The paper presents two-year follow-up outcomes. A working collaboration was established with two Western European Universities, the University of Marburg, Germany and the University of Dundee, UK. The innovative teaching methodology developed and used in the Department of Biochemistry at the University of Dundee was adopted considering the particular circumstances in the Medical University of Varna. The content of the basic biochemistry course was revised and expanded emphasizing the molecular basis of metabolic variation between different organs and molecular events and clinical medicine. New clinically case-oriented studies of biochemically-based disorders were introduced for the first time in the basic biochemistry course in the form of tutorials and discussion sessions with the students. The laboratory classes in biochemistry were deleted and replaced by demonstrations and clinical laboratory tests, together with tutorial and group activity sessions. New interactive small group methods were adopted in our teaching with the aim to ensure better understanding and accessibility of the teaching material. One free elective discipline entitled "Molecular biology in medicine" has been introduced. A system for obtaining students' opinions about the courses and new teaching methods using feedback questionnaires was adopted

Total hip arthroplasty improves pain and function but not physical activity

Background: People with hip osteoarthritis are likely to limit physical activity (PA) engagement due to pain and lack of function. Total hip arthroplasty (THA) reduces pain and improves function, potentially allowing increased PA. PA of THA patients was quantified to 12m post-operation. The hypothesis was that post-operatively levels of PA would increase. Methods: PA of 30 THA patients (67±7 years) was objectively measured pre-operatively and three and 12 months post-operation. Harris Hip Score (HHS), Oxford Hip Score (OHS) and six minute walk test (6MWT) were recorded. Mixed linear modelling was used to examine relationships of outcomes with time, baseline BMI, age, gender and baseline HHS. Results: Time was not a significant factor in predicting volume measures of PA, including sit-to-stand transitions, upright time and steps. Notably baseline BMI was a significant predictor of upright time, steps, largest number of steps in an upright bout, HHS and 6MWT. Baseline HHS helped predict longest upright bout, cadence of walking bouts >60s and OHS. The significant effect of participant as a random intercept in the model for PA outcomes suggested habituation from pre- to post-surgery. Conclusions: Volume measures of PA did not change from pre- to 12m post-surgery despite improvement in HHS, OHS and 6MWT. Baseline BMI was a more important predictor of upright activity and stepping than time. Pre- and post-operative PA promotion could be used to modify apparently habitual low levels of PA to enable full health benefits of THA to be gained

Social Values Related to the Development of Health and Care Guidance: Literature review for NICE by its Research Support Unit. Report of the Research Support Unit for the National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence develops guidance for the allocation of resources for services in clinical and public health and social care. It has a policy of social values underpinning this work that was last updated in 2008. This report is of a review of the literature on social values to help inform the further updating of this policy. The review involved a semi iterative search for literature that was then screened for ideas relevant to health and care guidance. These ideas and the main issues they raise are reported under eight major social value categories. Twenty one themes arising from the review are also provided. The literature raises many issues about the nature of social values that can be applied to guidance development. It needs to be emphasized that not all of these issues should necessarily be applied to guidance development. They are simply issues that have been raised in the literature and this review provides an opportunity for them to be considered. Many of the ideas that have been proposed are in tension with each other and could not all be achieved. It should also be emphasized that many of the issues raise considerable practical challenges in terms of methods, data and financial and timeliness. The review does not assume that any of these issues or ideas could or should necessarily be part of NICE’s policy on social values in guidance production. The review simply provides a list of ideas, issues and themes from the literature for consideration

Unique Residues Involved in Activation of the Multitasking Protease/Chaperone HtrA from Chlamydia trachomatis

DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly

There is an obstetrical dilemma: Misconceptions about the evolution of human childbirth and pelvic form

Compared to other primates, modern humans face high rates of maternal and neonatal morbidity and mortality during childbirth. Since the early 20th century, this "difficulty" of human parturition has prompted numerous evolutionary explanations, typically assuming antagonistic selective forces acting on maternal and fetal traits, which has been termed the "obstetrical dilemma." Recently, there has been a growing tendency among some anthropologists to question the difficulty of human childbirth and its evolutionary origin in an antagonistic selective regime. Partly, this stems from the motivation to combat increasing pathologization and overmedicalization of childbirth in industrialized countries. Some authors have argued that there is no obstetrical dilemma at all, and that the difficulty of childbirth mainly results from modern lifestyles and inappropriate and patriarchal obstetric practices. The failure of some studies to identify biomechanical and metabolic constraints on pelvic dimensions is sometimes interpreted as empirical support for discarding an obstetrical dilemma. Here we explain why these points are important but do not invalidate evolutionary explanations of human childbirth. We present robust empirical evidence and solid evolutionary theory supporting an obstetrical dilemma, yet one that is much more complex than originally conceived in the 20th century. We argue that evolutionary research does not hinder appropriate midwifery and obstetric care, nor does it promote negative views of female bodies. Understanding the evolutionary entanglement of biological and sociocultural factors underlying human childbirth can help us to understand individual variation in the risk factors of obstructed labor, and thus can contribute to more individualized maternal care