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The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and is a prominent therapeutic target for kinase inhibitors. The physiological roles of DCLK1 kinase activity and how it is regulated remain elusive. Here, we analyze the role of mammalian DCLK1 kinase activity in regulating microtubule binding. We found that DCLK1 autophosphorylates a residue within its C-terminal tail to restrict its kinase activity and prevent aberrant hyperphosphorylation within its microtubule-binding domain. Removal of the C-terminal tail or mutation of this residue causes an increase in phosphorylation within the doublecortin domains, which abolishes microtubule binding. Therefore, autophosphorylation at specific sites within DCLK1 has diametric effects on the molecule's association with microtubules. Our results suggest a mechanism by which DCLK1 modulates its kinase activity to tune its microtubule-binding affinity. These results provide molecular insights for future therapeutic efforts related to DCLK1's role in cancer development and progression.

Latin American nations are highly urbanised around a small number of megacities that account for the majority of these nations' productivity and population. Scholars of urban planning and economics argue these cities may be overly large, leading to environmental, transportation and housing issues that depress growth and increase economic inequality. We use fine-grained satellite data from 1992–2018 to document urban concentration in Latin America. We argue political decentralisation creates incentives to distribute urban populations more evenly throughout the territory. Our results demonstrate a strong empirical relationship between political decentralisation and lower urban concentration. We link our findings to literature on economic geography, political institutions and urbanisation, with broader implications for the politics of economic growth. [ABSTRACT FROM AUTHOR]

The nature of skill acquisition has long been of interest to music educators. This study considers the research context for relationships between aural dictation, sight singing, performance and composition skills. Then, relationships between these skill areas are quantitatively investigated using data from the Australian New South Wales Music 2 2010 and 2011 HSC examination tasks, which take place in the final year of secondary schooling. The results from the HSC data were analysed in three ways: raw results for each isolated skill, correlation analysis for each skill combination and comparative analysis of only top-achieving students. The study found that the highest correlations were between aural dictation and sight singing. Further analysis of top achieving students found that high achievement in multi-part aural dictation was the best predictor of high achievement in the other skill areas.

AMS student chapter at UD The University of Delaware's Department of Geography and Spatial Sciences launched a new meteorology and climatology major in the fall of 2015, creating a curriculum [...]

Calcific aortic valve disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis. This group identified CAVD as an actively regulated disease process in need of further study. As a result, the Alliance of Investigators on CAVD was formed to coordinate and promote CAVD research, with the goals of identifying individuals at risk, developing new therapeutic approaches, and improving diagnostic methods. The group is composed of cardiologists, geneticists, imaging specialists, and basic science researchers. This report reviews the current status of CAVD research and treatment strategies with identification of areas in need of additional investigation for optimal management of this patient population.

AbstractState capacity is a key concept for research in public policy and political science. Despite its importance, there is no broadly accepted measure of state capacity in the existing literature, and frequently used measures of capacity have not been examined for their validity. We begin with an explicit definition of state capacity – the state's ability to implement public policy – and connect this definition to a measurable outcome of state capacity – the state's taxation of income. We show that this measure, income taxes as a percentage of total tax revenue, is a useful indicator of state capacity and meets higher standards of measurement validity than other tax-based indicators. We also compare our measure to the most common existing indicators of state capacity to show that income taxation is a better theoretical and statistical measure of states’ effectiveness in policy implementation.

During the 2020 election, voting by mail greatly expanded due to concerns with COVID-19. While voting by mail is relatively easy for most individuals, who have United States Postal Service (USPS) residential mail service, it is much more difficult for those with nonstandard mail service. In this article, we examine how decisions made by the USPS in the latter part of the nineteenth and early twentieth centuries have resulted in deeply entrenched structural inequities in the access to mail services on the Navajo Nation in Arizona when compared to rural nonreservation communities. Most (89 percent) of current Post Offices were established during the settler colonial period, during which sites were chosen primarily to advance military objectives and serve the interests of Anglo-American settlers. The resulting inequitable pattern of postal access remains, resulting in inferior mail service on the Navajo Nation and adversely impacting many aspects of life. Post Offices are fewer and farther from each other on reservation communities; there are fewer service hours; and we show in a mail experiment that letters posted on reservations are slower and less likely to arrive. This research fits within the growing body of American political development research on path-dependent processes and "spatial racism" within geography. [ABSTRACT FROM AUTHOR]

Introduction: Predictive testing for BRCA1 or BRCA2 allows at-risk individuals to engage with appropriate screening and treatment services if a pathogenic mutation is identified. Previous studies have shown uptake of predictive testing to most commonly range between 20% and 40% (Table 2). This represents a missed cancer prevention opportunity. Possible explanations for this low uptake include lack of disclosure of at-risk status to relatives, lack of awareness of cancer genetics services, or patient preference. The goal of the current study was to investigate the uptake of BRCA1 or BRCA2 predictive testing in an Irish population. Methods: We performed a multicentre, retrospective analysis of 63 pedigrees from two Irish tertiary referral hospitals over a five-year period (2012-2017). Family pedigrees were reviewed to identify at-risk family members eligible for predictive BRCA1 or BRCA2 mutation testing as per international guidelines, and testing rates were determined. Results: A total of 1048 eligible individuals were identified, 318 (30.4%) proceeded to BRCA1 or BRCA2 germline testing including [215 (37.5%) females and 99 males (21.5%)]. Women were significantly more likely to test than men (T = 3.7, p <.0002). Uptake of testing was significant higher amongst first-degree relatives 45% (150/323) compared to 20% (50/258) amongst second degree relatives, and 10 % (33/317) amongst more distant relatives (F = 25.32, p < 0.00001). Conclusions: Uptake of BRCA1 OR BRCA2 mutation testing in Ireland is suboptimal, particularly amongst Irish males and distant relatives. Further research is needed to identify strategies which may improve uptake within current legal and ethical frameworks. [ABSTRACT FROM AUTHOR]