Complementary approaches to understanding the plant circadian clock

Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock

Algorithms for Stable Matching and Clustering in a Grid

We study a discrete version of a geometric stable marriage problem originally proposed in a continuous setting by Hoffman, Holroyd, and Peres, in which points in the plane are stably matched to cluster centers, as prioritized by their distances, so that each cluster center is apportioned a set of points of equal area. We show that, for a discretization of the problem to an $n\times n$ grid of pixels with $k$ centers, the problem can be solved in time $O(n^2 \log^5 n)$, and we experiment with two slower but more practical algorithms and a hybrid method that switches from one of these algorithms to the other to gain greater efficiency than either algorithm alone. We also show how to combine geometric stable matchings with a $k$-means clustering algorithm, so as to provide a geometric political-districting algorithm that views distance in economic terms, and we experiment with weighted versions of stable $k$-means in order to improve the connectivity of the resulting clusters.Comment: 23 pages, 12 figures. To appear (without the appendices) at the 18th International Workshop on Combinatorial Image Analysis, June 19-21, 2017, Plovdiv, Bulgari

Simple sequence repeat-based assessment of genetic diversity in 'Dimrit' and 'Gemre' grapevine accessions from Turkey

It is widely believed that Turkey has played an important role in the evolution of modern day grapes due to its unique geographical location with close proximity to the regions of grape diversity. Despite this, the rich grape germplasm found in Turkey has not been sufficiently analyzed genetically. In this study, 31 grapevine accessions from 'Dimrit' (or 'Dilmit') and 'Gemre' grape groups were genetically analyzed at eight SSR (microsatellite) loci (VVS2, VVMD5, VVMD7, VVMD24, VVMD27, VVMD28, VrZAG62 and VrZAG79) and for a number of ampeolographic characteristics. These analyses identified sufficient genetic diversity between these two grape groups that, in general, clustered separately in the dendrogram constructed based on the SSR data. However, the ecogeographical distribution and genetic relationship of the genotypes did not show any significant correlation. Two 'Gemre' accessions were determined as genetically identical. In addition, one case of synonym and several cases of homonym genotypes were identified. The results reported here are important first steps towards better characterization of these grape genotypes and would aid future germplasm management and breeding efforts.

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease

Cataloged from PDF version of article.Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation. © 2013 Elsevier B.V

International study on nurses' views and experiences of compassion

BACKGROUND: Compassion is considered the cornerstone of nursing practice. However, the recent failures in delivering high-quality compassionate nursing care in the UK's National Health Service have brought the topic of compassion to the attention of the public, service providers, policy makers and academics. AIM: The aim of this study was to explore the nurses' views and experiences of a number of compassion-related issues in nursing and describe similarities and differences at an international level as well as from the different nursing roles of the participating nurses. METHODS: An exploratory, cross-sectional descriptive study, using the International Online Compassion Questionnaire. A total of 1323 nurses from 15 countries completed the questionnaire. RESULTS: The majority of participants (59.5%) defined compassion as "Deep awareness of the suffering of others and wish to alleviate it" but definitions of compassion varied by country. Of participants, 69.6% thought compassion was very important in nursing and more than half (59.6%) of them argued that compassion could be taught. However, only 26.8% reported that the correct amount and level of teaching is provided. The majority of the participants (82.6%) stated that their patients prefer knowledgeable nurses with good interpersonal skills. Only 4.3% noted that they are receiving compassion from their managers. A significant relationship was found between nurses' experiences of compassion and their views about teaching of compassion. CONCLUSION: Our study is unique in identifying the views and experiences of nurses from 15 different countries worldwide. The findings reveal that compassion is neither addressed adequately in nursing education nor supported in the practice environment by managers. LIMITATIONS: Self-report bias was inherent to our survey study design. Furthermore, the individual cultural differences and similarities in the findings are difficult to extrapolate owing to the fact that our analysis was at country level, as well as at the level of the participating nurses. IMPLICATIONS FOR NURSING POLICY: Understanding the influence of culture on nurses' views about compassion is critical in the current multicultural healthcare environment and merits further research. This will potentially drive changes in nursing education (ensuring that compassion is taught to nurses) and in the way healthcare leaders and managers foster a compassionate culture within their organizations (e.g. by leading by example and compassionate to their staff). © 2016 International Council of Nurses

Enactment of compassionate leadership by nursing and midwifery managers: results from an international online survey

Aim To explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management. Method A cross- sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries. A total of complete 933 responses to a question related to which actions and behaviours indicated that a manager was exercising compassionate leadership were analysed for this paper. First, content analysis of the responses was conducted, and second, a relative distribution of the identified themes for the overall sample and for each participating country was calculated. Results Six main themes were identified describing the attributes of a compassionate leader: (1) Virtuous support, (2) Communication, (3) Personal virtues of the manager, (4) Participatory communication, (5) Growth/flourishing/ nurturing and (6) Team cohesion. The first three themes mentioned above collectively accounted for 63% of the responses, and can therefore be considered to be the most important characteristics of compassionate management behaviour. Conclusion The key indicators of compassionate management in nursing and midwifery which were identified emphasise approachability, active and sensitive listening, sympathetic responses to staff members’ difficulties (especially concerning child and other caring responsibilities), active support of and advocacy for the staff team and active problem solving and conflict resolution. While there were differences between the countries’ views on compassionate healthcare management, some themes were widely represented among different countries’ responses, which suggest key indicators of compassionate management that apply across culture

Using theatre in education in a traditional lecture oriented medical curriculum

<p>Abstract</p> <p>Background</p> <p>Lectures supported by theatrical performance may enhance learning and be an attractive alternative to traditional lectures. This study describes our experience with using theatre in education for medical students since 2001.</p> <p>Methods</p> <p>The volunteer students, coached by experienced students, were given a two-week preparation period to write and prepare different dramatized headache scenarios during three supervised meetings. A theatrical performance was followed by a student presentation about history taking and clinical findings in diagnosing headache. Finally, a group discussion led by students dealt with issues raised in the performance. The evaluation of the theatre in education lecture "A Primary Care Approach to Headache" was based on feedback from students.</p> <p>Results</p> <p>More than 90% of 43 responding students fully agreed with the statement "Theatrical performance made it easier to understand the topic". More than 90% disagreed with the statements "Lecture halls were not appropriate for this kind of interaction" and "Students as teachers were not appropriate". Open-ended questions showed that the lesson was thought of as fun, good and useful by most students. The headache questions in the final exam showed results that were similar to average exam results for other questions.</p> <p>Conclusion</p> <p>Using theatrical performance in medical education was appreciated by most students and may facilitate learning and enhance empathy and team work communication skills.</p

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Elucidating the source–sink relationships of zinc biofortification in wheat grains: a review

Zinc (Zn) concentration in wheat grains is generally low, with an average value of around 28–30 mg/kg. Therefore, increasing wheat grain Zn concentration for better human health is the focus of HarvestPlus global initiatives. Source–sink interactions have been intensively studied for decades to enhance crop yield potential, but less on grain nutritional quality. This review applies concepts of source, sink, and their interactions to the study of wheat grain Zn nutrition and biofortification. Increasing Zn sources to wheat (via soil and foliar application) could directly enlarge available Zn in vegetative tissues and grain Zn sink. Rational nitrogen (N) supply increases grain Zn accumulation (N‐Zn synergism), but phosphorus (P) input generally decreases (P‐Zn antagonism), and the potassium (K) effect is unclear. Conventional and genetic breeding have potential to stimulate Zn flow from source to sink (uptake from soil, root‐to‐shoot translocation, and remobilization). However, a rational manipulation to establish a well‐coordinated source–sink relationship is required to finally realize the grain Zn target (40–50 mg/kg) and increase on‐farm crop yield. Future studies should focus more on fertilization modes adopted by farmers (uses of compound, slow/controlled release, and organic and microbial fertilizers) and develop integrated agronomic and genetic strategies for Zn biofortification. A highly systematic and mechanistic model includes (a) migration paths of Zn (particularly from leaves to different grain parts) using isotopic labeling methods, (b) cross‐talks between Zn and carbon, N, P, K, or other divalent cations, (c) inherent physiological and biochemical processes of enzymes and signaling phytohormones, and (d) complex genetic systems governing Zn homeostasis and their relationships with other nutrients, signaling molecules, and increase or dilution/penalty of yield under different environmental conditions (soil, water, and future climatic changes) and managements (breeding and fertilization). These aspects require further elucidation to fully unravel the “black box” of Zn flow from source to sink