Mechanochemical modeling of dynamic microtubule growth involving sheet-to-tube transition

Microtubule dynamics is largely influenced by nucleotide hydrolysis and the resultant tubulin configuration changes. The GTP cap model has been proposed to interpret the stabilizing mechanism of microtubule growth from the view of hydrolysis effects. Besides, the microtubule growth involves the closure of a curved sheet at its growing end. The curvature conversion also helps to stabilize the successive growth, and the curved sheet is referred to as the conformational cap. However, there still lacks theoretical investigation on the mechanical-chemical coupling growth process of microtubules. In this paper, we study the growth mechanisms of microtubules by using a coarse-grained molecular method. Firstly, the closure process involving a sheet-to-tube transition is simulated. The results verify the stabilizing effect of the sheet structure, and the minimum conformational cap length that can stabilize the growth is demonstrated to be two dimers. Then, we show that the conformational cap can function independently of the GTP cap, signifying the pivotal role of mechanical factors. Furthermore, based on our theoretical results, we describe a Tetris-like growth style of microtubules: the stochastic tubulin assembly is regulated by energy and harmonized with the seam zipping such that the sheet keeps a practically constant length during growth.Comment: 23 pages, 7 figures. 2 supporting movies have not been uploaded due to the file type restriction

New Insight on Human Type 1 Diabetes Biology: nPOD and nPOD-Transplantation

The Juvenile Diabetes Research Foundation (JDRF) Network for Pancreatic Organ Donors with Diabetes (JDRF nPOD) was established to obtain human pancreata and other tissues from organ donors with type 1 diabetes (T1D) in support of research focused on disease pathogenesis. Since 2007, nPOD has recovered tissues from over 100 T1D donors and distributed specimens to approximately 130 projects led by investigators worldwide. More recently, nPOD established a programmatic expansion that further links the transplantation world to nPOD, nPOD-Transplantation; this effort is pioneering novel approaches to extend the study of islet autoimmunity to the transplanted pancreas and to consent patients for postmortem organ donation directed towards diabetes research. Finally, nPOD actively fosters and coordinates collaborative research among nPOD investigators, with the formation of working groups and the application of team science approaches. Exciting findings are emerging from the collective work of nPOD investigators, which covers multiple aspects of islet autoimmunity and beta cell biology

Make It Happen: Marketing Processes for Competitive Market Positioning of Firms in Transitional Economy

This paper presents some of the marketing processes, i.e. activities that firms in transitional economy can follow in the process of competitive market positioning. The main objective is to demonstrate that the practice of certain business processes, such as market orientation, market research, written marketing plans as a base for future business operations are correlated with creation of market positioning statements and thus increase the focus on market positioning in regards to competitors. This in addition, results in positive effects on profitability. Data are gathered through questionnaires and follow-up interviews. The results show that the analyzed processes have a positive outcome for firms in regards to competitive positioning. The creation of market positioning statement is found to be positively correlated with profitability. However, many of the firms in a transitional economy are slow in adapting to market changes, and have a selective approach to marketing activities. The most striking result is the more proactive approach of small and medium-sized enterprises in implementation of some of the marketing activities, like formal marketing planning and market research than large firms. Keywords: Domestic firms, Transitional economy, Market positioning, Market orientation, Formal marketing planning, Market researc

Defining High Risk: Cost-Effectiveness of Extended-Duration Thromboprophylaxis Following Major Oncologic Abdominal Surgery

PURPOSE: Extended duration thromboprophylaxis (EDTPPX) is the practice of prescribing antithrombotic therapy for 21 days after discharge, commonly used in surgical patients who are at high risk for venothromboembolism (VTE). While guidelines recommend EDTPPX, criteria are vague due to a paucity of data. The criteria can be further informed by cost-effectiveness thresholds. This study sought to determine the VTE incidence threshold for the cost-effectiveness EDTPPX compared to inpatient prophylaxis. METHODS: A decision tree was used to compare EDTPPX for 21 days after discharge to 7-days of inpatient-prophylaxis with base case assumptions based on an abdominal oncologic resection without complications in an otherwise healthy individual. Willingness to pay was set at $50,000/QALY. Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for costeffectiveness based on VTE incidence. RESULTS: EDTPPX was the dominant strategy when VTE probability exceeds 2.39$50,000/QALY, EDTPPX was the preferred strategy when VTE incidence exceeded 1.22% and 0.88% when using brand name or generic medication costs respectively. CONCLUSIONS: EDTPPX should be recommended whenever VTE incidence exceeds 2.39%. When post-discharge estimated VTE risk is 0.88%–2.39% patient preferences about self-injections and medication costs should be considered

Assembly dynamics of microtubules at molecular resolution

Microtubules are highly dynamic protein polymers that form a crucial part of the cytoskeleton in all eukaryotic cells. Although microtubules are known to self-assemble from tubulin dimers, information on the assembly dynamics of microtubules has been limited, both in vitro and in vivo, to measurements of average growth and shrinkage rates over several thousands of tubulin subunits. As a result there is a lack of information on the sequence of molecular events that leads to the growth and shrinkage of microtubule ends. Here we use optical tweezers to observe the assembly dynamics of individual microtubules at molecular resolution. We find that microtubules can increase their overall length almost instantaneously by amounts exceeding the size of individual dimers (8 nm). When the microtubule-associated protein XMAP215 (ref. 6) is added, this effect is markedly enhanced and fast increases in length of about 40-60 nm are observed. These observations suggest that small tubulin oligomers are able to add directly to growing microtubules and that XMAP215 speeds up microtubule growth by facilitating the addition of long oligomers. The achievement of molecular resolution on the microtubule assembly process opens the way to direct studies of the molecular mechanism by which the many recently discovered microtubule end-binding proteins regulate microtubule dynamics in living cells

An empirical investigation of the relationship between market orientation and MrkIS effectiveness in upscale hotels in Greece

This study examines the nature of relationships between marketing information systems (MktIS) effectiveness and market orientation (MO) dimensions. The study utilises a canonical correlation approach in order to determine the relationship between the two constructs. The results indicate that MO and MrkIS effectiveness are related concepts. More interesting is the relationship of customer and competitor orientation, especially with the external dimensions of the MrkIS effectiveness. These are the first empirical data that demonstrate a strong relationship between the customer and competitor orientation dimensions of the MO concept with the marketing procedural improvement and the two external dimensions of MrkIS effectiveness, namely customer knowledge and market responsiveness. On the other hand, interfunctional coordination is more closely related to internal climate of company's MrkIS effectiveness. Based on the results, managerial implications are discussed. Limitations of the study as well as future research directions are also addressed