Tyrosine phosphorylation of type Iγ phosphatidylinositol phosphate kinase by Src regulates an integrin–talin switch

Engagement of integrin receptors with the extracellular matrix induces the formation of focal adhesions (FAs). Dynamic regulation of FAs is necessary for cells to polarize and migrate. Key interactions between FA scaffolding and signaling proteins are dependent on tyrosine phosphorylation. However, the precise role of tyrosine phosphorylation in FA development and maturation is poorly defined. Here, we show that phosphorylation of type Iγ phosphatidylinositol phosphate kinase (PIPKIγ661) on tyrosine 644 (Y644) is critical for its interaction with talin, and consequently, localization to FAs. PIPKIγ661 is specifically phosphorylated on Y644 by Src. Phosphorylation is regulated by focal adhesion kinase, which enhances the association between PIPKIγ661 and Src. The phosphorylation of Y644 results in an ∼15-fold increase in binding affinity to the talin head domain and blocks β-integrin binding to talin. This defines a novel phosphotyrosine-binding site on the talin F3 domain and a “molecular switch” for talin binding between PIPKIγ661 and β-integrin that may regulate dynamic FA turnover

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

The birth of airplane stability theory

Airplane stability theory was born at the end of the XIX century and matured around 100 years ago, when airplanes were hardly controllable yet. The success and safety of flights in the pioneer years depended upon largely unknown stability and control characteristics. Understanding the modes of airplane motion has been of paramount importance for the development of aviation. The contributions made by a few scientists in the decades preceding and following the first flight by the Wright brothers set the concepts and equations that, with minor notation aspects, have remained almost unchanged till present day.Magraner Rullan, JP.; Martinez-Val, R. (2014). The birth of airplane stability theory. Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering. 228(9):1498-1506. doi:10.1177/0954410013494139S149815062289PERKINS, C. D. (1970). Development of airplane stability and control technology /1970 Von Karman Lecture/. Journal of Aircraft, 7(4), 290-301. doi:10.2514/3.44167Abzug, M. J., & Larrabee, E. E. (2002). Airplane Stability and Control, Second Edition. doi:10.1017/cbo9780511607141Graham, W. R. (1999). Asymptotic analysis of the classical aircraft stability equations. The Aeronautical Journal, 103(1020), 95-103. doi:10.1017/s0001924000027792Bryan, G. H., & Williams, W. E. (1904). The Longitudinal Stability of Aerial Gliders. Proceedings of the Royal Society of London, 73(488-496), 100-116. doi:10.1098/rspl.1904.0017Wegener, P. P. (1997). What Makes Airplanes Fly? doi:10.1007/978-1-4612-2254-5Pradeep, S., & Kamesh, S. (1999). Does the Phugoid Frequency Depend on Speed? Journal of Guidance, Control, and Dynamics, 22(2), 372-373. doi:10.2514/2.4391Phillips, W. F. (2000). Phugoid Approximation for Conventional Airplanes. Journal of Aircraft, 37(1), 30-36. doi:10.2514/2.2586Pamadi, B. N. (2004). Performance, Stability, Dynamics, and Control of Airplanes, Second Edition. doi:10.2514/4.862274Ananthkrishnan, N., & Ramadevi, P. (2002). Consistent Approximations to Aircraft Longitudinal Modes. Journal of Guidance, Control, and Dynamics, 25(4), 820-824. doi:10.2514/2.4952McRuer, D. T., Graham, D., & Ashkenas, I. (1990). Aircraft Dynamics and Automatic Control. doi:10.1515/978140085598

Cohort study of Western Australia computed tomography utilisation patterns and their policy implications

Background: Computed tomography (CT) scanning is a relatively high radiation dose diagnostic imaging modality with increasing concerns about radiation exposure burden at the population level in scientific literature. This study examined the epidemiology of adult CT utilisation in Western Australia (WA) in both the public hospital and private practice settings, and the policy implications. Methods: Retrospective cohort design using aggregate adult CT data from WA public hospitals and Medical Benefits Schedule (MBS) (mid-2006 to mid-2012). CT scanning trends by sex, age, provider setting and anatomical areas were explored using crude CT scanning rates, age-standardised CT scanning rates and Poisson regression modelling. Results: From mid-2006 to mid-2012 the WA adult CT scanning rate was 129 scans per 1,000 person-years (PY). Females were consistently scanned at a higher rate than males. Patients over 65 years presented the highest scanning rates (over 300 scans per 1,000 PY). Private practice accounted for 73% of adult CT scans, comprising the majority in every anatomical area. In the private setting females predominately held higher age-standardised CT scanning rates than males. This trend reversed in the public hospital setting. Patients over 85 years in the public hospital setting were the most likely age group CT scanned in nine of ten anatomical areas. Patients in the private practice setting aged 85+ years were relatively less prominent across every anatomical area, and the least likely age group scanned in facial bones and multiple areas CT scans.Conclusion: In comparison to the public hospital setting, the MBS subsidised private sector tended to service females and relatively younger patients with a more diverse range of anatomical areas, constituting the majority of CT scans performed in WA. Patient risk and subsequent burden is greater for females, lower ages and some anatomical areas. In the context of a national health system, Australia has various avenues to monitor radiation exposure levels, improve physician training and modify funding mechanisms to ensure individual and population medical radiation exposure is as low as reasonably achievable

Analysis and characterization of heparin impurities

This review discusses recent developments in analytical methods available for the sensitive separation, detection and structural characterization of heparin contaminants. The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007–2008 spawned a global crisis resulting in extensive revisions to the pharmacopeia monographs on heparin and prompting the FDA to recommend the development of additional physicochemical methods for the analysis of heparin purity. The analytical chemistry community quickly responded to this challenge, developing a wide variety of innovative approaches, several of which are reported in this special issue. This review provides an overview of methods of heparin isolation and digestion, discusses known heparin contaminants, including OSCS, and summarizes recent publications on heparin impurity analysis using sensors, near-IR, Raman, and NMR spectroscopy, as well as electrophoretic and chromatographic separations

IMG 305 - PEMBUNGKUSAN MAKANAN NOV.05.

We discuss the use of Agent-based Modelling for the development and testing of theories about emergent social phenomena in marketing and the social sciences in general. We address both theoretical aspects about the types of phenomena that are suitably addressed with this approach and practical guidelines to help plan and structure the development of a theory about the causes of such a phenomenon in conjunction with a matching ABM. We argue that research about complex social phenomena is still largely fundamental research and therefore an iterative and cyclical development process of both theory and model is to be expected. To better anticipate and manage this process, we provide theoretical and practical guidelines. These may help to identify and structure the domain of candidate explanations for a social phenomenon, and furthermore assist the process of model implementation and subsequent development. The main goal of this paper was to make research on complex social systems more accessible and help anticipate and structure the research process

The COVID-19 pandemic and its global effects on dental practice. An international survey

Objectives A multicentre survey was designed to evaluate the impact of COVID-19 outbreak on dental practice worldwide, estimate the COVID-19 related symptoms/signs, work attitudes and behaviour and the routine use of protective measures and personal protective equipment (PPE). Methods A global survey using a standardized questionnaire with research groups from 36 countries was designed. The questionnaire was developed and pretested during April 2020 and contained three domains: 1) personal data; 2) COVID-19 positive rate and symptoms/signs presumably related to the coronavirus; 3) working conditions and PPE adopted after the outbreak. Countries’ data were grouped by the country positive rate (CPR) during the survey period and by Gross-National-Income per capita. An ordinal multinomial logistic regression model was carried out with COVID-19 self-reported rate referred by dental professionals as dependent variable to assess the association with questionnaire items. Results A total of 52,491 questionnaires were returned with a male/female ratio of 0.63. Out of the total respondents, 7,859 dental professionals (15%) reported symptoms/signs compatible with COVID-19. More than half of the sample (n=27,818; 53%) stated to use FFP2/N95 masks, while 21,558 (41.07%) used eye protection. In the bivariate analysis, CPR and N95/FFP2 were significantly associated (OR=1.80 95%CI=1.60/2.82 and OR=5.20 95%CI=1.44/18.80, respectively), while Gross-National-Income was not statistically associated with CPR (OR=1.09 95%CI=0.97/1.60). The same significant associations were observed in the multivariate analysis. Conclusions Oral health service provision has not been significantly affected by COVID-19, although access to routine dental care was reduced due to country-specific temporary lockdown periods. While the dental profession has been identified at high-risk, the reported rates of COVID-19 for dental professionals were not significantly different to those reported for the general population in each country. These findings may help to better plan oral health care for future pandemic events

How channels evolve: A historical explanation

This paper addresses the nature and drivers of channel evolution. The evolution of the Australian IT industry is investigated using historical methods. Identification of channel issues and descriptions of its evolution are drawn from trade publications, augmented by interviews with channel participants and analyzed using a combination of content, causal and narrative event analysis to sequence, link and interpret the flow of events that have shaped this channel. We find that market, product, and influence and to a lesser degree commercial agreements, have shaped the development of this channel. These emanate primarily from within the Australian IT industry, but to some degree are also influenced by international events. The paper concludes with a discussion as to how these findings can be extrapolated and used to illustrate the deep co-evolutionary processes that characterize distribution channels. © 2011