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"Robertson, B"
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The politics of protest in hybrid regimes : managing dissent in post-communist Russia
\"Since the end of the Cold War, more and more countries feature political regimes that are neither liberal democracies nor closed authoritarian systems. Most research on these hybrid regimes focuses on how elites manipulate elections to stay in office, but in places as diverse as Bolivia, Georgia, Kyrgyzstan, Serbia, Thailand, Ukraine, and Venezuela, protest in the streets has been at least as important as elections in bringing about political change. The Politics of Protest in Hybrid Regimes builds on previously unpublished data and extensive fieldwork in Russia to show how one high-profile hybrid regime manages political competition in the workplace and in the streets. More generally, the book develops a theory of how the nature of organizations in society, state strategies for mobilizing supporters, and elite competition shape political protest in hybrid regimes\"--Provided by publisher.
Book
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.
MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance analysis.
Journal Article
Putin v. the people : the perilous politics of a divided Russia
What do ordinary Russians think of Putin? Who are his supporters? And why might their support now be faltering? Alive with the voices and experiences of ordinary Russians and elites alike, Sam Greene and Graeme Robertson craft a compellingly original account of contemporary Russian politics. Telling the story of Putin's rule through pivotal episodes such as the aftermath of the \"For Fair Elections\" protests, the annexation of Crimea, and the War in Eastern Ukraine, Greene and Robertson draw on interviews, surveys, social media data, and leaked documents to reveal how hard Putin has to work to maintain broad popular support, while exposing the changing tactics that the Kremlin has used to bolster his popularity. Unearthing the ambitions, emotions, and divisions that fuel Russian politics, this book illuminates the crossroads to which Putin has led his country and shows why his rule is more fragile than it appears.
Book
Legislatures, Cooptation, and Social Protest in Contemporary Authoritarian Regimes
A key debate in the new literature on authoritarianism concerns the role of institutions in general and legislatures in particular. While much of the literature accepts that authoritarian legislatures matter, there is little agreement as to why and how. In this article, we argue that a key function of authoritarian legislatures is to help leaders reduce social protest. In contrast to existing literature, which stresses the representative function of authoritarian legislatures, we argue that legislatures reduce social protest by providing rent-seeking opportunities to key opposition elites who, in return for access to these spoils, demobilize their supporters. We test this argument using original data on the distribution of leadership positions in 83 Russian regional legislatures and two new datasets on opposition protest in Russia. Our findings suggest that legislative cooptation may extend the lifespan of authoritarian regimes by helping to reduce antiregime protest.
Journal Article
MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice
MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1β, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1β release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.
Journal Article
سر الثراء = The secret to wealth : دراسات
في هذا الكتاب المذهل سر الثراء الجزء الثالث قام كلا من سونيل تولسياني وبراين تريسي بجمع قادة اليوم القادمين من جميع أنحاء العالم للكشف عن إستراتيجياتهم المتطورة لمساعدتك على أن تصبح ثريا بشكل كبير. داخل هذه الصفحات، ستجد تقنيات وأدوات لتغيير الحياة لتحقيق أحلامك. سواء كنت تريد أن تصبح رائد أعمال ومليونير فائق الثروة، أو تشتري العقارات دون استخدام أموالك الخاصة، أو تتقاعد ثريا في سن أصغر، أو تقوم بجذب عملائك ذوي الدخل المرتفع، أو إعداد نفسك لتربح مبالغ ضخمة من الدخل السلبي، فهذا الكتاب مناسب لك تماما.
Book
Subnational Appointments in Authoritarian Regimes: Evidence from Russian Gubernatorial Appointments
Elections are among the most important and least understood institutions in contemporary authoritarian regimes. Theoretically, electoral authoritarian regimes should have an informational advantage that makes them more robust than other types of authoritarian regimes, but much empirical evidence suggests otherwise. In this article we offer a new perspective on why this might be the case. Specifically, we consider how authoritarian elections influence a ruler’s choices in making cadre appointments. We argue that the imperative of winning authoritarian elections forces authoritarian leaders to prioritize the appointment of politically loyal cadres, who can help the regime win elections. This choice often comes at the expense of appointing officials who are competent at making good public policy and promoting economic development, factors that may contribute to long-term regime stability. We test this theory using an original dataset of gubernatorial appointments in one leading contemporary authoritarian regime, Russia.
Journal Article
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
A selective, small-molecule inhibitor of NLRP3 suppresses activation of the inflammasome
in vitro
and
in vivo
and attenuates inflammatory disease.
The NOD-like receptor (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production
in vivo
and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in
ex vivo
samples from individuals with Muckle–Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.
Journal Article
Control of glutamine metabolism by the tumor suppressor Rb
Retinoblastoma (Rb) protein is a tumor suppressor that is dysregulated in a majority of human cancers. Rb functions to inhibit cell cycle progression in part by directly disabling the E2F family of cell cycle-promoting transcription factors. Because the
de novo
synthesis of multiple glutamine-derived anabolic precursors is required for cell cycle progression, we hypothesized that Rb also may directly regulate proteins involved in glutamine metabolism. We examined glutamine metabolism in mouse embryonic fibroblasts (MEFs) isolated from mice that have triple knock-outs (TKO) of all three Rb family members (Rb-1, Rbl1 and Rbl2) and found that loss of global Rb function caused a marked increase in
13
C-glutamine uptake and incorporation into glutamate and tricarboxylic acid cycle (TCA) intermediates in part via upregulated expression of the glutamine transporter ASCT2 and the activity of glutaminase 1 (GLS1). The Rb-controlled transcription factor E2F-3 altered glutamine uptake by direct regulation of ASCT2 mRNA and protein expression, and E2F-3 was observed to associate with the ASCT2 promoter. We next examined the functional consequences of the observed increase in glutamine uptake and utilization and found that glutamine exposure potently increased oxygen consumption, whereas glutamine deprivation selectively decreased ATP concentration in the Rb TKO MEFs but not the wild-type (WT) MEFs. In addition, TKO MEFs exhibited elevated production of glutathione from exogenous glutamine and had increased expression of gamma-glutamylcysteine ligase relative to WT MEFs. Importantly, this metabolic shift towards glutamine utilization was required for the proliferation of Rb TKO MEFs but not for the proliferation of the WT MEFs. Last, addition of the TCA cycle intermediate α-ketoglutarate to the Rb TKO MEFs reversed the inhibitory effects of glutamine deprivation on ATP, GSH levels and viability. Taken together, these studies demonstrate that the Rb/E2F cascade directly regulates a major energetic and anabolic pathway that is required for neoplastic growth.
Journal Article