p70 S6 kinase and actin dynamics: A perspective

p70 S6 kinase (p70S6K), a member of the AGC serine/threonine kinase family, was initially identified as a key player, together with its downstream effector S6, in the regulation of cellular growth and survival. The p70S6K protein has emerged in recent years as a multifunctional protein which also regulates the actin cytoskeleton and thus plays a role in cell migration. This new function is through two important activities of p70S6K, namely actin cross-linking and Rac1 and Cdc42 activation. The testis is critically dependent on an intricate balance of fundamental cellular processes such as adhesion, migration, and differentiation. It is increasingly evident that Rho GTPases and actin binding proteins play fundamental roles in regulating spermatogenesis within the testis. In this review, we will discuss current findings of p70S6K in the control of actin cytoskeleton dynamics. In addition, the potential role of p70S6K in spermatogenesis and testicular function will be highlighted

OxyCAP UK: Oxyfuel Combustion - academic Programme for the UK

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2 M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling

People and Things on the Move: Domestic Material Culture, Poverty and Mobility in Victorian London

© 2016, The Author(s). The development of what Mayne and Lawrence (Urban History 26: 325–48, 1999) termed “ethnographic” approaches to studying nineteenth-century households and urban communities has gathered momentum in recent years. As such research agendas have taken hold and been applied to new contexts, so critiques, methodological developments, and new intellectual and theoretical currents, have provided opportunities to enhance and develop approaches. This article contributes to this on-going process. Drawing upon household archaeological research on Limehouse, a poor neighborhood in Victorian London, and inspired by the theoretical insights provided by the “new mobilities paradigm,” it aims to place “mobility” as a central and enabling intellectual framework for understanding the relationships between people, place, and poverty. Poor communities in nineteenth-century cities were undeniably mobile and transient. Historians and archaeologists have often regarded this mobility as an obstacle to studying everyday life in such contexts. However, examining temporal routines and geographical movements across a variety of time frames and geographical scales, this article argues that mobility is actually key to understanding urban life and an important mechanism for interpreting the fragmented material and documentary traces left by poor households in the nineteenth-century metropolis.We are grateful to the UK’s Arts and Humanities Research Council who funded the research upon which this paper is based (Grant Reference AH/E002285/1): ‘Living in Victorian London: Towards a Material History of Everyday Domestic Life in the Nineteenth-Century Metropolis

The effect on endothelial function of vitamin C during methionine induced hyperhomocysteinaemia

BACKGROUND: Manipulation of total homocysteine concentration with oral methionine is associated with impairment of endothelial-dependent vasodilation. This may be caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant vitamin and free radical scavenger. We hypothesised that if the impairment of endothelial function related to experimental hyperhomocysteinaemia was free radically mediated then co-administration of vitamin C should prevent this. METHODS: Ten healthy adults took part in this crossover study. Endothelial function was determined by measuring forearm blood flow (FBF) in response to intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg) plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink plus placebo tablets. Study drugs were administered at 9 am on each study date, a minimum of two weeks passed between each study. Homocysteine (tHcy) concentration was determined at baseline and after 4 hours. Endothelial function was determined at 4 hours. Responses to the vasoactive substances are expressed as the area under the curve of change in FBF from baseline. Data are mean plus 95% Confidence Intervals. RESULTS: Following oral methionine tHcy concentration increased significantly versus placebo. At this time endothelial-dependent responses were significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were unchanged. Co-administration of vitamin C did not alter the increase in homocysteine or prevent the impairment of endothelial-dependent responses (31.4 [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo) CONCLUSIONS: This study demonstrates that methionine increased tHcy with impairment of the endothelial-dependent vasomotor responses. Administration of vitamin C did not prevent this impairment and our results do not support the hypothesis that the endothelial impairment is mediated by adverse oxidative stress

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

OxyCAP UK: Oxyfuel Combustion - academic Programme for the UK

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling

Factors associated with breastfeeding cessation in nursing mothers in a peer support programme in Eastern Lancashire

<p>Abstract</p> <p>Background</p> <p>The UK has one of the lowest breastfeeding rates worldwide and in recent years the Government has made breastfeeding promotion one of its priorities. The UNICEF UK Baby Friendly Initiative is likely to increase breastfeeding initiation but not duration. Other strategies which involve provision of support for breastfeeding mothers in the early weeks after birth are therefore required to encourage UK mothers to breastfeed for the recommended duration. This paper examines the effects of maternal socio-demographic factors, maternal obstetric factors, and in-hospital infant feeding practices on breastfeeding cessation in a peer support setting.</p> <p>Methods</p> <p>Data on mothers from Blackburn with Darwen (BwD) and Hyndburn in Eastern Lancashire who gave birth at the Royal Blackburn Hospital and initiated breastfeeding while in hospital were linked to the Index of Multiple Deprivation (IMD). The data were analysed to describe infant feeding methods up to 6 months and the association between breastfeeding cessation, and maternal factors and in-hospital infant feeding practices.</p> <p>Results</p> <p>The mean breastfeeding duration was 21.6 weeks (95% CI 20.86 to 22.37 weeks) and the median duration was 27 weeks (95% CI 25.6 to 28.30 weeks). White mothers were 69% more likely to stop breastfeeding compared with non-White mothers (HR: 0.59; 95% CI, 0.52 to 0.67 [White mothers were the reference group]). Breastfeeding cessation was also independently associated with parity and infant feeding practices in hospital. There were no significant associations between breastfeeding cessation and marital status, mode of delivery, timing of breastfeeding initiation and socio-economic deprivation.</p> <p>Conclusion</p> <p>In this study ethnicity, parity and in-hospital infant feeding practices remained independent predictors of breastfeeding cessation in this peer support setting. However other recognised predictors such as marital status, mode of delivery, timing of breastfeeding initiation and socio-economic deprivation were not found to be associated with breastfeeding cessation.</p

Structural Basis of Gate-DNA Breakage and Resealing by Type II Topoisomerases

Type II DNA topoisomerases are ubiquitous enzymes with essential functions in DNA replication, recombination and transcription. They change DNA topology by forming a transient covalent cleavage complex with a gate-DNA duplex that allows transport of a second duplex though the gate. Despite its biological importance and targeting by anticancer and antibacterial drugs, cleavage complex formation and reversal is not understood for any type II enzyme. To address the mechanism, we have used X-ray crystallography to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation. A high resolution structure of the complex captured by a novel antibacterial dione reveals two drug molecules intercalated at a cleaved B-form DNA gate and anchored by drug-specific protein contacts. Dione release generated drug-free cleaved and resealed DNA complexes in which the DNA gate instead adopts an unusual A/B-form helical conformation with a Mg2+ ion repositioned to coordinate each scissile phosphodiester group and promote reversible cleavage by active-site tyrosines. These structures, the first for putative reaction intermediates of a type II topoisomerase, suggest how a type II enzyme reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomerase-targeting therapeutics

Comparing patient characteristics and treatment processes in patients receiving physical therapy in the United States, Israel and the Netherlands. Cross sectional analyses of data from three clinical databases

<p>Abstract</p> <p>Background</p> <p>Many assume that outcomes from physical therapy research in one country can be generalized to other countries. However, no well designed studies comparing outcomes among countries have been conducted. In this exploratory study, our goal was to compare patient demographics and treatment processes in outpatient physical therapy practice in the United States, Israel and the Netherlands.</p> <p>Methods</p> <p>Cross-sectional data from three different clinical databases were examined. Data were selected for patients aged 18 years and older and started an episode of outpatient therapy between January 1^st2005 and December 31^st2005. Results are based on data from approximately 63,000 patients from the United States, 100,000 from Israel and 12,000 from the Netherlands.</p> <p>Results</p> <p>Age, gender and the body part treated were similar in the three countries. Differences existed in episode duration of the health problem, with more patients with chronic complaints treated in the United States and Israel compared to the Netherlands. In the United States and Israel, physical agents and mechanical modalities were applied more often than in the Netherlands. The mean number of visits per treatment episode, adjusted for age, gender, and episode duration, varied from 8 in Israel to 11 in the United States and the Netherlands.</p> <p>Conclusion</p> <p>The current study showed that clinical databases can be used for comparing patient demographic characteristics and for identifying similarities and differences among countries in physical therapy practice. However, terminology used to describe treatment processes and classify patients was different among databases. More standardisation is required to enable more detailed comparisons. Nevertheless the differences found in number of treatment visits per episode imply that one has to be careful to generalize outcomes from physical therapy research from one country to another.</p