Mutation of Arabidopsis SPLICEOSOMAL TIMEKEEPER LOCUS1 Causes Circadian Clock Defects

The circadian clock plays a crucial role in coordinating plant metabolic and physiological functions with predictable environmental variables, such as dusk and dawn, while also modulating responses to biotic and abiotic challenges. Much of the initial characterization of the circadian system has focused on transcriptional initiation, but it is now apparent that considerable regulation is exerted after this key regulatory step. Transcript processing, protein stability, and cofactor availability have all been reported to influence circadian rhythms in a variety of species. We used a genetic screen to identify a mutation within a putative RNA binding protein (SPLICEOSOMAL TIMEKEEPER LOCUS1 [STIPL1]) that induces a long circadian period phenotype under constant conditions. STIPL1 is a homolog of the spliceosomal proteins TFP11 (Homo sapiens) and Ntr1p (Saccharomyces cerevisiae) involved in spliceosome disassembly. Analysis of general and alternative splicing using a high-resolution RT-PCR system revealed that mutation of this protein causes less efficient splicing of most but not all of the introns analyzed. In particular, the altered accumulation of circadian-associated transcripts may contribute to the observed mutant phenotype. Interestingly, mutation of a close homolog of STIPL1, STIP-LIKE2, does not cause a circadian phenotype, which suggests divergence in function between these family members. Our work highlights the importance of posttranscriptional control within the clock mechanism. © 2012 American Society of Plant Biologists. All rights reserved

"Meniscal" scar as a landmark for the joint line in revision total knee replacement

$\textbf{AIM}$: To determine whether tissue identified at the joint line was actually remnant "meniscal" scar tissue or not. $\textbf{METHODS}$: Nine patients undergoing revision knee surgery following informed consent had meniscal scar tissue sent to the histology department for analyses. All revisions were performed where joint line had been raised or lowered at earlier surgery. Although preoperative radiographic evaluations suggested that the joint line had been altered, intraoperatively there was scar tissue at the level of the recreated joint line. This scar tissue has traditionally been described as meniscal scar, and to identify the origins of this tissue, samples were sent for histological analyses. The tissue samples were stored in formalin, and embedded and sectioned before undergoing histochemical staining. All samples underwent macroscopic and microscopic examination by a histopathologist who was blind to the study aims. The specific features that were examined included tissue organisation, surface and central composition, cellular distribution including histiocytes, nuclear ratio and vasculature. Atypical and malignant features, inflammation and degeneration were specifically looked for. A statistical review of the study was performed by a biomedical statistician. $\textbf{RESULTS}$: The histological findings for the nine patients showing the macroscopic and microscopic findings, and the conclusion are outlined in a Table. The histological analyses were reviewed to determine whether the tissue samples were likely to be meniscal scar tissue. The response was yes (2, 22%), no (6, 67%) and maybe (1, 11%) based on the conclusions. The results were "yes" when on macroscopy, firm cream tissue was identified. In these two "yes" samples, microscopic analyses showed organised fibrous tissue with focal degenerative areas with laminated pattern associated with histiocytes peripherally but no inflammation. The "no" samples were assessed macroscopically and microscopically and were deemed to have appearances representing fibrous synovial tissue and features in keeping with degenerate scar tissue or connective tissue. One sample was indeterminate and microscopically contained fibro-collagenous tissue with synovial hyperplasia. It also contained some degenerate hyalinised tissue that may represent cartilage, but the appearances were not specific. $\textbf{CONCLUSION}$: Based on our pilot study, we recommend reliance on a number of markers to identify the joint line as outlined above, and to exercise caution in using the "meniscal" scar

The Role of n-3 Fatty Acids in Cardiometabolic Risk

The work described in this thesis addresses two questions relating to benefits of dietary omega-3 fatty acids (n-3 LCPUFA). Accretion of research knowledge indicates that adequate n-3 LCPUFA intakes may be instrumental in maintaining good health throughout life, including in the optimisation of cardiovascular health. Sources of n-3 LCPUFA traditionally include fish oils but concern regarding long-term sustainability of fish stocks has led to investigation of alternative sources. Krill oil, obtained from the crustacean Euphausia superba, contains n-3 fatty acids as phospholipids and triglycerides, astaxanthin and related carotenoid pigments, and has been proposed as a more effective alternative than triglyceride oils. Some foods rich in n-3-LCPUFA, including prawns, also contain cholesterol; concern regarding possible adverse health effects of such dietary cholesterol has led to public health advice to limit intake of these potentially beneficial foodstuffs. These questions are addressed in two food intake studies in male volunteers by monitoring markers of cardiovascular health, food intake and biochemical markers of compliance. Firstly, prawns and a white fish control were compared for effects on lipoprotein profiles and other markers. Dietary supplementation with 225 g prawns daily for 4 weeks was associated with a decrease in ApoB of 7.8mg/dL compared an increase (+2.4 mg/dL) for the white fish control. Participants with BMI > 25 kg/m2 also showed a reduction in plasma TAG (0.17 mmol/L) compared with baseline following prawn intake; those receiving the control showed an increase in plasma TAG (0.30 mmol/L), a decrease in HDL-C, and increases in VLDL-C and sdLDL-C. No overall adverse effect was found for prawns compared with processed white fish. Secondly, effects were compared of fish oil and krill oil on cardiometabolic profiles of a cohort of men with metabolic syndrome, using anthropometric measurements, biochemical markers of cardiovascular health and assessments of food intake. Krill oil and fish oil at the doses used showed no overall difference in effect on MetS markers after 6 weeks; correlations between magnitude of reduction and baseline measurement were observed in both groups for TAG, fasting glucose, NEFA and sdLDL after 3 weeks on both supplements, and for glucose and cholesterol after 6 weeks of fish oil. Comparison of analytical methods was also undertaken during both studies; use of a point-of-care system using capillary blood correlated well with plasma biochemistry using venous blood, while the Hirano method for sdLDL measurement correlated favourably with more labour-intensive centrifugation techniques. Limitations of the methods used are discussed, and proposals put forward for future work, including improving compliance through the use of newly emerging technologies such as metabolomics

Interventional cardiology : Cost-effectiveness of PCI guided by fractional flow reserve

Coronary revascularization strategies have been evaluated in numerous clinical trials. As coronary revascularization has become more common, concerns over financial costs have increased

A Daoist perspective on leadership: reputation-building in Chinese SMEs

This is the author accepted manuscript. The final version is available from Emerald via the DOI in this recordPurpose This article examines the influence of Daoist nothingness on leadership in growing Chinese SMEs. Daoism is based on a ‘letting-go’ approach through maintaining inherent openness, which challenges goal-oriented and hierarchical approaches typical of Western and Confucian leadership theories. This facilitates the cross-fertilization of ideas related to the effective management of smaller firms. Design/methodology/approach This study focuses on SME leaders in a group of twelve growing SMEs in the Shanghai logistics industry in China. Narrative and semi-structured interviews explored emerging aspects beyond the established model of leadership associated with reputation-building. This led to in-depth, thick descriptions, broadening our understanding of leadership and reputation building. Findings SME leaders follow nothingness by continuously adopting a letting-go approach which spontaneously fosters reputation-building. By maintaining inherent openness, nothingness functions as an enabling principle that mobilises multi-beings leading to reputation-building in unintended ways. Research limitations/implications A greater plurality of empirical and methodological contexts in Western and non-Western countries helps to understand the dynamics and intersection of Daoist nothingness, leadership and reputation-building. Practical implications SME leaders recounted how they discursively practised nothingness for extended periods in their everyday practice. The study shows the significance of nothingness for SME leaders who aspire to grow their businesses by reputation-building among salient stakeholders. Social implications Daoist nothingness provides insights into the distinctive approach of Chinese SME leaders and their relationships with local and distant stakeholders. By engaging in active non-action they relax pre-determined intentions and immerse themselves in the process of leading, where the intrinsic connections between goals and processes are automatically animated. Such an approach differs from the top-down and goal-oriented approach to leadership adopted in many western SMEs. Originality/value This paper makes two theoretical contributions. First, it indicates the powerful influence of Daoist nothingness on leadership by drawing on the broader context of entrepreneurship in Chinese SMEs. Second, it enriches existing concepts such as reputation by endowment and reputation borrowing by demonstrating how Daoist nothingness silently fosters both local reputation and generalized reputation

Household Disposal of Pharmaceuticals as a Pathway for Aquatic Contamination in the United Kingdom

Pharmaceuticals are produced and used in increasingly large volumes every year. With this growth comes concern about the fate and effects of these compounds in the environment. The discovery of pharmaceuticals in the aquatic environment has stimulated research in the last decade. A wide range of pharmaceuticals has been found in fresh and marine waters, and it has recently been shown that even in small quantities, some of these compounds have the potential to cause harm to aquatic life. The primary pathway into the environment is the use and disposal of medicines; although much of the research in the area currently focuses on the removal of pharmaceuticals during sewage treatment processes, disposal via household waste might be a significant pathway requiring further research. To investigate the household disposal of unused and expired pharmaceuticals as a source of pharmaceutical compounds in the environment, we carried out a survey and interviewed members of 400 households, predominantly from southeastern England. We used the information on when and how they disposed of unfinished pharmaceuticals to construct a conceptual model to assess the pathways of human pharmaceuticals into the environment. The model demonstrated that disposal of unused pharmaceuticals, either by household waste or via the sink or toilet, may be a prominent route that requires greater attention

The tensions of defining and developing thought leadership within knowledge-intensive firms

This is the final version. Available on open access from Emerald via the DOI in this record.Design/methodology/approach We review the academic and practitioner literature on thought leadership to provide a rich oversight of how it is defined and can be understood by separating inputs, creation processes and outcomes. We also draw on qualitative data from 12 in-depth interviews with senior leaders of professional service firms. Purpose A major part of knowledge management for knowledge-intensive firms such as professional service firms is the increasing focus on thought leadership. Despite being a well-known term, it is poorly defined and analysed in the academic and practitioner literature. As a result, we seek to answer three questions. First, what is thought leadership? Second, what tensions exist when seeking to create thought leadership in knowledge-based organisations? Third, what further research is needed about thought leadership? We call for cross-disciplinary and academic-practitioner approaches to understanding the field of thought leadership. Findings Through analysing and building on previous understandings of the concept, we redefine thought leadership as: “Knowledge from a trusted, eminent and authoritative source that is actionable and provides valuable solutions for stakeholders.” We find and explore nine tensions that developing thought leadership creates and propose a framework for understanding how to engage with thought leadership at the industry/macro, organisational/meso and individual/micro levels. We propose a research agenda based on testing propositions derived from new theories to explain thought leadership, including leadership, reducing risk, signaling quality, and managing social networks, as well as examining the suggested ways to resolve different tensions. Originality/value We are the first to separate out thought leadership from its inputs, creation processes and outcomes. We show new organisational paradoxes within thought leadership and show how they can play out at different levels of analysis when implementing a thought leadership strategy. This work on thought leadership is set in a relatively under-explored context for knowledge management researchers, namely, knowledge-intensive professional service firms

A Bayesian palaeoenvironmental transfer function model for acidified lakes

A Bayesian approach to palaeoecological environmental reconstruction deriving from the unimodal responses generally exhibited by organisms to an environmental gradient is described. The approach uses Bayesian model selection to calculate a collection of probability-weighted, species-specific response curves (SRCs) for each taxon within a training set, with an explicit treatment for zero abundances. These SRCs are used to reconstruct the environmental variable from sub-fossilised assemblages. The approach enables a substantial increase in computational efficiency (several orders of magnitude) over existing Bayesian methodologies. The model is developed from the Surface Water Acidification Programme (SWAP) training set and is demonstrated to exhibit comparable predictive power to existing Weighted Averaging and Maximum Likelihood methodologies, though with improvements in bias; the additional explanatory power of the Bayesian approach lies in an explicit calculation of uncertainty for each individual reconstruction. The model is applied to reconstruct the Holocene acidification history of the Round Loch of Glenhead, including a reconstruction of recent recovery derived from sediment trap data.The Bayesian reconstructions display similar trends to conventional (Weighted Averaging Partial Least Squares) reconstructions but provide a better reconstruction of extreme pH and are more sensitive to small changes in diatom assemblages. The validity of the posteriors as an apparently meaningful representation of assemblage-specific uncertainty and the high computational efficiency of the approach open up the possibility of highly constrained multiproxy reconstructions

Representing complex data using localized principal components with application to astronomical data

Often the relation between the variables constituting a multivariate data space might be characterized by one or more of the terms: ``nonlinear'', ``branched'', ``disconnected'', ``bended'', ``curved'', ``heterogeneous'', or, more general, ``complex''. In these cases, simple principal component analysis (PCA) as a tool for dimension reduction can fail badly. Of the many alternative approaches proposed so far, local approximations of PCA are among the most promising. This paper will give a short review of localized versions of PCA, focusing on local principal curves and local partitioning algorithms. Furthermore we discuss projections other than the local principal components. When performing local dimension reduction for regression or classification problems it is important to focus not only on the manifold structure of the covariates, but also on the response variable(s). Local principal components only achieve the former, whereas localized regression approaches concentrate on the latter. Local projection directions derived from the partial least squares (PLS) algorithm offer an interesting trade-off between these two objectives. We apply these methods to several real data sets. In particular, we consider simulated astrophysical data from the future Galactic survey mission Gaia.Comment: 25 pages. In "Principal Manifolds for Data Visualization and Dimension Reduction", A. Gorban, B. Kegl, D. Wunsch, and A. Zinovyev (eds), Lecture Notes in Computational Science and Engineering, Springer, 2007, pp. 180--204, http://www.springer.com/dal/home/generic/search/results?SGWID=1-40109-22-173750210-

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand