Gene Targeting Implicates Cdc42 GTPase in GPVI and Non-GPVI Mediated Platelet Filopodia Formation, Secretion and Aggregation

Background: Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation. Methodology/Principal Findings: We utilized the Mx-cre;Cdc42 lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42 +/+ mice. Platelets isolated from Cdc42 2/2, as compared to Cdc42 +/+, mice exhibited (a) diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b) inhibition of filopodia formation on immobilized CRP or fibrinogen, (c) inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d) inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e) minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42 2/2 mice compared with Cdc42 +/+ mice. Conclusion/Significance: Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion an

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Civil Rights for Some, Stereotyping for Others: Two Views on the Open Housing Movement of the 1960s

The modern Civil Rights Movement in the United States was successful in addressing long-standing inequities in political, economic, and other civil rights for African Americans and prompted similar changes for other minority groups. Yet, one of the unintended consequences of the interpretation of the civil rights legislation enacted by Congress was that the federal government began classifying people by race so as to determine whether they merited protection under the new laws. This article examines the process created by U. S. government agencies to determine whether the new civil rights laws had been violated, the way in which the legislation was interpreted in the judicial system, and the consequences for Americans of Eastern and Southern European heritage

REMEMBERING POLAND, BUT NOT POLONIA: THE DEVELOPMENT OF POLISH AMERICAN HISTORICAL MEMORY

The leading edge of the mass migration from Poland to the USA which began in the 1870s was comprised mostly of ethnic Poles from the German-occupied partition, but these were superseded in the following decade by arrivals from the Austrian partition, who were in turn eclipsed in the latter 1890s by immigrants from the Russian-controlled regions. To the immigrants there were specific differences in regional culture, dialect, and traditions by which they clearly separated themselves into three or more groups. Thus, one of the major challenges facing immigrants was how to create a new Polish American identity from such a diverse collection of subgroups. In particular, the paper focuses on the forms of cultural and identity transmission from generation to generation. It suggests that by emphasizing Old World customs and celebrations, i.e. by remembering Poland, but not Polonia, the immigrants have failed to create a distinctly Polonian identity independent of Poland

When Policy Meets Politics: An Analysis of U.S. Immigration Issues, 1998–2018

International migration is a major issue in many parts of the world today. In the United States, with its history of immigration, it has been a recurring theme in political discussion for over two centuries. This article addresses three issues: (1) providing data to establish the size, composition, and recent trends in immigration to the U.S. today, (2) a review of 2018 U.S. public opinion polls on immigration, and (3) an interpretation of why a subject where most Americans generally agree has caused protracted emotional and divisive debates over the past two decades