University of Sunderland

About: University of Sunderland is a education organization based out in Sunderland, United Kingdom. It is known for research contribution in the topics: Context (language use) & Population. The organization has 1786 authors who have published 3897 publications receiving 94152 citations.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Extension to the North Atlantic oscillation using early instrumental pressure observations from Gibraltar and south-west Iceland

Abstract: Early instrumental pressure measurements from Gibraltar and the Reykjavik area of Iceland have been used to extend to 1821 the homogeneous pressure series at the two locations In winter the two sites are located close to the centres of action that comprise the North Atlantic Oscillation (NAO). The extended 'winter half-year' record of the NAO enables recent changes in the record to be placed in the context of the period 1823-1996 The period since the early 1970s is the most prolonged positive phase of the oscillation and the late 1980s and early 1990s is the period with the highest values (strongest westerlies) The winter of 1995-1996 marked a dramatic switch in the index, with the change from 1994-1995 being the greatest change recorded from one year to the next since the series began in 1923. (The extended Gibraltar and Reykjavik monthly pressures and the NAO series can be found on the Climatic Research Unit home page. www.cru.uea-ac.uk.

Guidelines on the irritable bowel syndrome: mechanisms and practical management

Abstract: Background: IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. Aim: To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. Methods: Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. Results: Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients’ concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5-HT 3 antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5-HT 4 agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. Conclusions: Better ways of identifying which patients will respond to specific treatments are urgently needed.

High-intensity running in English FA Premier League soccer matches

Abstract: The aims of this study were to (1) determine the activity profiles of a large sample of English FA Premier League soccer players and (2) examine high-intensity running during elite-standard soccer matches for players in various playing positions. Twenty-eight English FA Premier League games were analysed during the 2005–2006 competitive season (n = 370), using a multi-camera computerised tracking system. During a typical match, wide midfielders (3138 m, s = 565) covered a greater distance in high-intensity running than central midfielders (2825 m, s = 473, P = 0.04), full-backs (2605 m, s = 387, P < 0.01), attackers (2341 m, s = 575, P < 0.01), and central defenders (1834 m, s = 256, P < 0.01). In the last 15 min of a game, high-intensity running distance was ∼20% less than in the first 15-min period for wide midfielders (467 m, s = 104 vs. 589 m, s = 134, P < 0.01), central midfielders (429 m, s = 106 vs. 534 m, s = 99, P < 0.01), full-backs (389 m, s = 95 vs. 481 m, s = 114, P < 0.01), attacker...