tan Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Wed, 13 Nov 2019 09:45:01 +0000 Invitation Only Research Event 28 November 2019 - 1:30pm to 3:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Annette Bohr, Associate Fellow, Russia and Eurasia Programme, Chatham HouseKassymkhan Kapparov, Founder, Economist.kzJoanna Lillis, Reporter, The Guardian, The Economist and The IndependentKate Mallinson, Associate Fellow, Russia and Eurasia Programme, Chatham HouseDossym Satpayev, Director, Kazakhstan Risk Assessment Group; Member of the Presidium, Kazakhstan Council on International RelationsChair: James Nixey, Head, Russia and Eurasia Programme, Chatham House At face value at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as seeking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev wants to ensure Kazakhstan does not depart from the course he has set while safeguarding Kazakhstan’s stability in the context of multiple and evolving domestic and international challenges. But this is easier said than done. Is Kazakhstan ready for the challenges of the future? This event marks the launch of Chatham House’s major report Kazakhstan: Tested by Transition. Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
tan Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Tue, 26 Nov 2019 11:22:01 +0000 27 November 2019 A partial handover of political power through an orchestrated transition takes Kazakhstan into uncharted territory. Will it be able to pursue modernization and reform, and break from its authoritarian past? Read online Download PDF Annette Bohr Associate Fellow, Russia and Eurasia Programme Dr Nigel Gould-Davies Associate Fellow, Russia and Eurasia Programme, Chatham House @Nigelgd1 Google Scholar Kate Mallinson Associate Fellow, Russia and Eurasia Programme @Kate_Mallinson1 James Nixey Director, Russia and Eurasia Programme @jamesnixey Birgit Brauer Analyst, Writer and Journalist Covering Central Asia Nargis Kassenova Senior Fellow, Davis Center for Russian and Eurasian Studies, Harvard University Joanna Lillis Kazakhstan-Based Journalist Reporting on Central Asia Dosym Satpayev Independent Political Analyst and the Director of the Kazakhstan Risks Assessment Group Kazakhstan: Tested by Transition Kazakhstan is at a turning point in its history. At face value, at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as looking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev seeks to ensure Kazakhstan does not depart from the course he has set, while safeguarding regime stability in the context of multiple and evolving domestic and international challenges. This is easier said than done.The uncertainty around this project is substantial, especially considering a ‘rowback’ decree just seven months after Nazarbayev’s resignation, limiting the powers of his anointed successor, Kassym-Jomart Tokayev. How long can Tokayev credibly remain president considering such a transparent undermining of his authority? Is Nazarbayev, in fact, grooming his daughter, Dariga Nazarbayeva, another relative or a power player from outside the family for the leadership in the longer term? Will the ‘Kazakh tandem’ of Nazarbayev and Tokayev function effectively, or will tensions and conflicts arise between them as many claim is happening already? How will the leadership cope with the protest mood now manifest on the streets of Kazakhstan, and address the political and socio-economic grievances fuelling this discontent? How might the political transition play out if Nazarbayev were to suddenly exit the political scene altogether?And what is the long-term transition plan for the time when Nazarbayev has departed, and how effective will it be?As Kazakhstan enters uncharted territory, the purpose of this report is twofold. First, to make the case for the West to devote more attention to Kazakhstan. The country’s relative importance in Central Asia, and as the constant focus of intense attention from China and Russia, suggests that the West is wrong to direct so little time and diplomatic effort and so few resources towards it. This is not so much a miscalculation (that would be to assume there had been a calculation in the first place) as a misstep through neglect, presupposing that the future will resemble the present – with Kazakhstan remaining stable internally, relatively inconsequential geopolitically but nevertheless a friendly ally to the West. In fact, the country’s trajectory over the next few years is of potentially strategic import. This is because even its political semi-transition presents the West with a rare opportunity to push back against the global rise of authoritarianism, in a state that is open to rational argument and economic logic.The second function of the report is to serve as a well-intentioned message to the leadership of Kazakhstan. The research undertaken by the report’s eight authors shows that Kazakhstan is at risk of failing to achieve the goals its leadership has set for the country. As significant as it has been, the partial stepping aside of Nazarbayev by no means guarantees the modernization and renewal that he and his successor have promised. Far deeper political, economic and social reforms will be needed if Kazakhstan is to meet the growing challenges to its stability, prosperity and development. Street protests since Nazarbayev’s resignation have demonstrated a level of popular disaffection far higher than the authorities acknowledge. The leadership needs to bridge the disconnect between the rulers and the ruled and start listening to its people.To avoid slipping into decline, and to resist external pressures and geopolitical overtures that could diminish the sovereignty that its leadership is so determined to safeguard, Kazakhstan needs new faces – innovators and reformers – throughout every level of the administration, as well as new ideas. This report is intended to help with the ‘ideas’ part of that proposition. It also includes a series of recommendations for Western governments and institutions and for the Kazakhstan government. Department/project Russia and Eurasia Programme, Internal Dynamics and External Interests in Central Asia Full Article
tan Kazakhstan: Reaching Out to Central Asian Neighbours By feedproxy.google.com Published On :: Wed, 04 Dec 2019 10:21:03 +0000 4 December 2019 Annette Bohr Associate Fellow, Russia and Eurasia Programme Despite its regional outreach, Kazakhstan’s diplomatic priority will remain Russia, China, and Europe. 2019-12-04-Kaz.jpg Kazakhstan's President Kassym-Jomart Tokayev, Kazakh Majilis Chairman Nurlan Nigmatulin and ex-president Nursultan Nazarbayev at an inauguration ceremony in parliament. Photo: Pavel AleksandrovTASS via Getty Images. Leaders of the resource-rich Central Asian region have the propensity to remain in power until mortality dictates otherwise. Much like the UK and Brexit, however, few wanted to see Central Asia’s longest reigning ruler, Kazakhstan’s septuagenarian president Nursultan Nazarbayev, crash out without a deal.The sudden departure of the country’s official leader of the nation with no clear succession plan could have led to investment chaos, intra-elite fighting and the unravelling in a matter of months of a system he had built over decades, à la Uzbekistan following the death of long-serving autocrat Islam Karimov in 2016.In order to avoid just such a ‘no-deal’ scenario and ensure the continuity of his policies, in March Nazarbayev carefully choreographed his own resignation and the election of a hand-picked successor, President Kassym-Jomart Tokayev, while retaining plum positions and powers for himself.Tokayev’s assumption of the presidency was accompanied by protesters in the streets, increasing wealth inequality, rising Sinophobia among rank-and-file Kazakhstanis, a hard-to-kick economic dependence on oil revenues and a lack of clarity as to which leader—the old or the new president—would actually be calling the shots. But, amidst this plethora of concerns, as argued in a recent Chatham House report, Kazakhstan: Tested by Transition, one bright spot has been the tangible growth of intra-Central Asian cooperation, with the Nazarbayev-Tokayev ruling duo appearing eager to improve the regional dialogue.Kazakhstan has long shaped its identity as a Eurasian state that has acted as more of an intermediary between Russia and Central Asia than as an integral part of the Central Asian region. But since 2017, in particular, Kazakhstan has been increasingly looking for opportunities to boost hitherto weak cooperation with its Central Asian neighbours. While this is first and foremost owing to the liberalization of Uzbekistan’s large market, there are other factors at work that get less airplay.One such factor is a perceptible disentangling from the Kremlin’s policy directions as Kazakhstan has come to view Russia’s foreign policy as increasingly neo-colonial. The example of the Russia-led Eurasian Economic Union is in many respects more off-putting than inspiring, and Nur-Sultan does not want to be locked tightly into the union’s economic orbit. And in distancing itself slightly from Moscow in order to limit Russian leverage in its affairs, Nur-Sultan has shown itself to be more open to Central Asian regional initiatives.As part of the leadership’s plan to offset oil dependence, Kazakhstan aspires to become the transport, telecommunications and investment hub for Eurasian integration. The intense focus on connectivity and the development of logistical arteries and infrastructure could have the knock-on effect of boosting trade within the Central Asian region and reducing transit times, which are currently greater than in most other parts of the globe.In addition, demographic trends and educational shifts that favour ethnic Kazakhs, together with a growing ethno-nationalist narrative, have allowed the state’s leadership to identify more closely with Kazakhstan’s common Central Asian heritage and, by extension, a common Central Asian region—although Kazakhstan’s leadership still remains eager to demonstrate that the country is not just another ‘stan’. The coming to power of President Mirziyoyev in Uzbekistan appears to have made Kazakhstan more aware of the interconnectedness of the two countries in terms of geographical location and potential economic complementarities, as well as culture and history.Not least, there is a growing recognition among the Central Asian states themselves—including isolationist Turkmenistan to a degree—that deepening regional trade is mutually beneficial, especially given the constraints associated with Russia’s economic problems. The strengthening of Kazakhstan’s ties with Uzbekistan has slowly kick-started regional cooperation as a whole: trade turnover between the Central Asian states in 2018 grew by 35 per cent on the previous year.But both Kazakhstan and Uzbekistan are keen to stress that there is no discussion of integration or institutionalization, not least because previous attempts at integration have been overtaken by Russia, leaving Central Asia without its own coordinating body.The official consensus in Kazakhstan is that Uzbekistan’s economic reforms after years of isolation will spur ‘a healthy rivalry’ and ultimately boost Kazakhstan’s own economy, in so far as the competition for foreign investment will require both countries to work harder to improve their respective business and regulatory environments.At the unofficial level, however, some Kazakhstani analysts view Uzbekistan’s rise as potentially unprofitable, given the possible diversion of some investments and market activity from Kazakhstan to Uzbekistan. Moreover, Uzbekistan has the advantage of having undergone a clear change of executive, while it remains unclear which developments await Kazakhstan once First President Nazarbayev leaves the scene for good.It can certainly be argued that Uzbekistan does pose a potential threat in the long-term to Kazakhstan’s entrenched position as Central Asia’s economic powerhouse: Uzbekistan’s population is one-and-a-half times bigger, even if its nominal GDP is three times smaller. Uzbekistan has a bigger market and a well-developed industrial sector, and is already the regional leader in terms of security. But it is not as though the world’s interest is moving from Kazakhstan to Uzbekistan; rather, Uzbekistan is in the process of trying to catch up.Despite this relatively upbeat picture, Kazakhstan’s combined trade with the other Central Asian states accounts for less than 5 per cent of its total volume of foreign trade—a figure that cannot begin to equal its trade with Russia, China, and Europe. As a result, Kazakhstan will continue to give greater importance to positioning itself as a global player than as a regional leader.This article was originally published in The Diplomat. Full Article
tan Can Uzbekistan’s President Meet Raised Expectations? By feedproxy.google.com Published On :: Wed, 11 Dec 2019 14:14:05 +0000 11 December 2019 Kate Mallinson Associate Fellow, Russia and Eurasia Programme @Kate_Mallinson1 Shavkat Mirziyoyev has implemented a number of important reforms, but is now entering a more hazardous period. 2019-12-11-Uz.jpg Shavkat Mirziyoyev in June. Photo: Getty Images. In the three years since Shavkat Mirziyoyev was elected president of Uzbekistan, he has embarked on a wide-ranging reform process including currency liberalization, eliminating forced labour and abolishing exit visas. This has encouraged foreign investors and the population, but a rare protest last week over natural gas and electricity shortages shows that the Uzbek population’s faith in change under the new leadership could be wearing thin, while foreign direct investment that adds real value to the economy is in short supply.When Mirziyoyev came to power, Uzbekistan was on the verge of bankruptcy. A former prime minister of 13 years, and a pragmatic economist, the new president set on a rapid course to open Uzbekistan up to its neighbours and remove barriers to trade and foreign investment. The alacrity and ambition of the reform process and the monetary and economic liberalization has at times been overwhelming for lawyers and businesses. However, allowing the free movement of capital, people and goods are natural moves to boost an economy after 20 years of stasis. The country is now immersed in the more challenging and substantive phase of development, including privatization, the breakup of monopolies and capital markets reform. Despite a marked increase in foreign direct investment, the country is not receiving the investment it needs. Much of it comes from Russia or China through bilateral arrangements, with debt from China washing through state-owned banks and state-owned enterprises. Uzbekistan’s debt to China has increased three times since the end of 2016.Meanwhile, European and US companies still appear unsure about the business environment and the staying power of reforms. A lack of consistent policy, alongside hastily drafted decrees and legislation that often require presidential decrees to clarify their meaning as well, as opaque carve outs, are further deterring Western investors. A workforce that is still in transition from a Soviet to a free market approach exacerbates the situation.Opposition within the government to implementation of some of the reforms, as well as competing government interests, have led to backtracking on some reforms (such as free and unrestricted currency convertibility) and creeping protectionism in some sectors. Some reforms simply get lost in the long chain from presidential decree to implementation. After 2018, import tariffs were abolished but recently, a list of protected domestically produced products has been drawn up raising concerns that vested interests are replacing state monopolies with private ones.Despite progress on the economic front, political and social reform has lagged. Uzbekistan is still largely run by senior cadres from the previous administration of Islam Karimov. While the government has attracted younger reformers, often returning from abroad, it has also been rehabilitating key figures from the Karimov years that were implicated in corruption scandals. Progressive senior officials, such as the former general prosecutor Otabek Murodov, have been removed with little explanation as to why; trials take place behind closed doors.The new leadership has transformed the media environment, but the country still lacks objective analytical reporting. Direct criticism of the president or the ruling family remains taboo. Economic and monetary liberalization has come at a cost to the population in the form of double-digit inflation, while utility prices are moving to the level of the free market. Popular discontent is growing at the grass roots level and some hark back to the stability of the former government, in spite of its reputation for appalling human rights treatment.Small and innovative steps have been taken to improve the rule of law, but more can be done, including introducing transparency over judicial processes and ensuring regional authorities have less impunity before the law. An initiative to address the issue of conflict of interest – whereby mayors, senators and other senior civil servants have been able to benefit commercially from their positions during an era of government economic stimulus – would signal a commitment to fundamental reform.With great promises of political and economic reform, the government has set a high bar for itself. A continuing paternalistic form of governance, with its restricted civil society freedoms, human rights, stifling bureaucracy and corruption, against continuing lack of opportunities, will clash with the expectations of a growing young population.Mirziyoyev is trying to make the parliamentary elections on 22 December, the first during his presidency, more dynamic. Yet no opposition parties have been able to emerge to serve as a check on the executive branch. A product of the system he ostensibly wishes to reform, Mirziyoyev will need to prioritize the strengthening of independent institutions to deliver results to his expectant people. Full Article
tan In a COVID-19 World, Russia Sticks to International Distancing By feedproxy.google.com Published On :: Sun, 29 Mar 2020 20:49:14 +0000 29 March 2020 Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world. 2020-03-29-Coronavirus-Russia-Moscow Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images. Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.Russian trolls never sleepRussia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.Self-isolation, Kremlin styleMeanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia. Full Article
tan Nonsynonymous SNPs in LPA homologous to plasminogen deficiency mutants represent novel null apo(a) alleles [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Plasma lipoprotein (a) [Lp(a)] levels are largely determined by variation in the LPA gene, which codes for apo(a). Genome-wide association studies (GWASs) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels, although their effect on apo(a) function is unknown. We investigated two such variants, R990Q and R1771C, which were present in four null Lp(a) individuals, for structural and functional effects. Sequence alignments showed the R990 and R1771 residues to be highly conserved and homologous to each other and to residues associated with plasminogen deficiency. Structural modeling showed both residues to make several polar contacts with neighboring residues that would be ablated on substitution. Recombinant expression of the WT and R1771C apo(a) in liver and kidney cells showed an abundance of an immature form for both apo(a) proteins. A mature form of apo(a) was only seen with the WT protein. Imaging of the recombinant apo(a) proteins in conjunction with markers of the secretory pathway indicated a poor transit of R1771C into the Golgi. Furthermore, the R1771C mutant displayed a glycosylation pattern consistent with ER, but not Golgi, glycosylation. We conclude that R1771 and the equivalent R990 residue facilitate correct folding of the apo(a) kringle structure and mutations at these positions prevent the proper folding required for full maturation and secretion. To our knowledge, this is the first example of nonsynonymous variants in LPA being causative of a null Lp(a) phenotype. Full Article
tan Is CYP2C70 the key to new mouse models to understand bile acids in humans? [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Full Article
tan Problem Notes for SAS®9 - 65918: SAS Workflow Services fails to respond after a com.sas.workflow.engine.policy.PolicyExecutionException error occurs for a workflow instance By feedproxy.google.com Published On :: Wed, 6 May 2020 13:42:50 EST When the problem occurs, you are unable to perform any workflow actions in a SAS solution that uses SAS Workflow Services. Full Article WEBINFPLTFM+SAS+Web+Infrastructure+Platf
tan Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs. Full Article
tan Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis By diabetes.diabetesjournals.org Published On :: 2020-01-23T08:19:19-08:00 Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role, and that hepatic amino acid metabolism and glucagon are linked in a mutual feed-back cycle, the liver-alpha cell axis. On this background, we hypothesized that hepatic steatosis might impair glucagon’s action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia.We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism during basal and high physiological levels of glucagon. The degree of steatosis was evaluated from liver biopsies.Total RNA sequencing of liver biopsies revealed perturbations in the expression of genes predominantly involved in amino acid metabolism in the obese steatotic individuals. This group was also characterized by fasting hyperglucagonemia, hyperaminoacidemia and an absent lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals.Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism resulting in increased amino acid concentrations as well as increased glucagon secretion providing a likely explanation of fatty liver-associated hyperglucagonemia. Full Article
tan Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence (>=49%) in an Inbred Population of Pakistan By diabetes.diabetesjournals.org Published On :: 2020-04-29T13:57:29-07:00 Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance. Full Article
tan Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy. Full Article
tan The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high. Full Article
tan Inhibition of glycosphingolipid biosynthesis reverts multidrug resistance by differentially modulating ABC transporters in chronic myeloid leukemias [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias. Full Article
tan Targeting the polyamine pathway—“a means” to overcome chemoresistance in triple-negative breast cancer [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Triple-negative breast cancer (TNBC) is characterized by its aggressive biology, early metastatic spread, and poor survival outcomes. TNBC lacks expression of the targetable receptors found in other breast cancer subtypes, mandating use of cytotoxic chemotherapy. However, resistance to chemotherapy is a significant problem, encountered in about two-thirds of TNBC patients, and new strategies are needed to mitigate resistance. In this issue of the Journal of Biological Chemistry, Geck et al. report that TNBC cells are highly sensitive to inhibition of the de novo polyamine synthesis pathway and that inhibition of this pathway sensitizes cells to TNBC-relevant chemotherapy, uncovering new opportunities for addressing chemoresistance. Full Article
tan Nicotine and Insulin Resistance: When the Smoke Clears By diabetes.diabetesjournals.org Published On :: 2012-12-01 Mandeep BajajDec 1, 2012; 61:3078-3080Commentary Full Article
tan Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors By diabetes.diabetesjournals.org Published On :: 2020-04-01 Mariam AlatrachApr 1, 2020; 69:681-688Pathophysiology Full Article
tan Insulin Resistance and Type 2 Diabetes By diabetes.diabetesjournals.org Published On :: 2012-04-01 Roy TaylorApr 1, 2012; 61:778-779Commentary Full Article
tan Metabolic Endotoxemia Initiates Obesity and Insulin Resistance By diabetes.diabetesjournals.org Published On :: 2007-07-01 Patrice D. CaniJul 1, 2007; 56:1761-1772Obesity Studies Full Article
tan One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation By diabetes.diabetesjournals.org Published On :: 2016-10-01 Marlou L. DirksOct 1, 2016; 65:2862-2875Metabolism Full Article
tan Benefits of face masks and social distancing in Tuberculosis - a lesson learnt the hard way during the COVID-19 pandemic. By feeds.bmj.com Published On :: Friday, May 8, 2020 - 10:36 Full Article
tan The rule of law and maritime security: understanding lawfare in the South China Sea By feedproxy.google.com Published On :: Wed, 04 Sep 2019 13:46:35 +0000 4 September 2019 , Volume 95, Number 5 Douglas Guilfoyle Read online Does the rule of law matter to maritime security? One way into the question is to examine whether states show a discursive commitment that maritime security practices must comply with international law. International law thus provides tools for argument for or against the validity of certain practices. The proposition is thus not only that international law matters to maritime security, but legal argument does too. In this article, these claims will be explored in relation to the South China Sea dispute. The dispute involves Chinese claims to enjoy special rights within the ‘nine-dash line’ on official maps which appears to lay claim to much of the South China Sea. Within this area sovereignty remains disputed over numerous islands and other maritime features. Many of the claimant states have engaged in island-building activities, although none on the scale of China. Ideas matter in such contests, affecting perceptions of reality and of what is possible. International law provides one such set of ideas. Law may be a useful tool in consolidating gains or defeating a rival's claims. For China, law is a key domain in which it is seeking to consolidate control over the South China Sea. The article places the relevant Chinese legal arguments in the context of China's historic engagement with the law of the sea. It argues that the flaw in China's approach has been to underestimate the extent to which it impinges on other states' national interests in the maritime domain, interests they conceptualize in legal terms. Full Article
tan Trust boss gave misleading information to GMC about consultant who was unfairly dismissed By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 15:31 Full Article
tan Covid-19: South Korea relaxes social distancing after the number of new cases drops below 10 a day By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 16:26 Full Article
tan MEIZITANG OBAT PELANGSING BADAN HERBAL ALAMI - Rahasia Pria By investing.96.lt Published On :: Sun, 22 Jan 2017 11:02:23 UTC Meizitang Obat Pelangsing Badan Herbal Merupakan Suplemen Diet Herbal Berbentuk SOFTGEL Yang Sangat Berkhasiat Melangsingkan Tubuh Dengan Cepat Dan Aman, Full Article Sports and Health
tan Corporate Raiding in Russia, Ukraine and Kazakhstan By feedproxy.google.com Published On :: Tue, 15 Oct 2019 09:45:02 +0000 Invitation Only Research Event 5 November 2019 - 9:00am to 1:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agenda - Corporate Raiding in Russia, Ukraine and Kazakhstanpdf | 105.48 KB Event participants John Patton, Argentem CreekRachel Cook, Peters & PetersTom Mayne, University of ExeterOlga Bischof, Brown Rudnick LLPIsobel Koshiw, Global WitnessAnton Moiseienko, RUSI The widespread practice of illicit acquisition of a business or part of a business in the former Soviet states, known as ‘reiderstvo’ or asset-grabbing, is a major risk that disincentivises investment in the region.It is distinct from the way corporate raiding occurs in the West and enabled by factors such as corruption and weak protection of property rights.This roundtable will assess the practice of corporate raiding in Russia, Ukraine and Kazakhstan: its evolution over time, knock-on effects and potential solutions. The speakers will also address the implications for the UK legal system and possible policy responses. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
tan Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Wed, 13 Nov 2019 09:45:01 +0000 Invitation Only Research Event 28 November 2019 - 1:30pm to 3:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Annette Bohr, Associate Fellow, Russia and Eurasia Programme, Chatham HouseKassymkhan Kapparov, Founder, Economist.kzJoanna Lillis, Reporter, The Guardian, The Economist and The IndependentKate Mallinson, Associate Fellow, Russia and Eurasia Programme, Chatham HouseDossym Satpayev, Director, Kazakhstan Risk Assessment Group; Member of the Presidium, Kazakhstan Council on International RelationsChair: James Nixey, Head, Russia and Eurasia Programme, Chatham House At face value at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as seeking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev wants to ensure Kazakhstan does not depart from the course he has set while safeguarding Kazakhstan’s stability in the context of multiple and evolving domestic and international challenges. But this is easier said than done. Is Kazakhstan ready for the challenges of the future? This event marks the launch of Chatham House’s major report Kazakhstan: Tested by Transition. Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
tan Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Tue, 26 Nov 2019 11:22:01 +0000 27 November 2019 A partial handover of political power through an orchestrated transition takes Kazakhstan into uncharted territory. Will it be able to pursue modernization and reform, and break from its authoritarian past? Read online Download PDF Annette Bohr Associate Fellow, Russia and Eurasia Programme Dr Nigel Gould-Davies Associate Fellow, Russia and Eurasia Programme, Chatham House @Nigelgd1 Google Scholar Kate Mallinson Associate Fellow, Russia and Eurasia Programme @Kate_Mallinson1 James Nixey Director, Russia and Eurasia Programme @jamesnixey Birgit Brauer Analyst, Writer and Journalist Covering Central Asia Nargis Kassenova Senior Fellow, Davis Center for Russian and Eurasian Studies, Harvard University Joanna Lillis Kazakhstan-Based Journalist Reporting on Central Asia Dosym Satpayev Independent Political Analyst and the Director of the Kazakhstan Risks Assessment Group Kazakhstan: Tested by Transition Kazakhstan is at a turning point in its history. At face value, at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as looking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev seeks to ensure Kazakhstan does not depart from the course he has set, while safeguarding regime stability in the context of multiple and evolving domestic and international challenges. This is easier said than done.The uncertainty around this project is substantial, especially considering a ‘rowback’ decree just seven months after Nazarbayev’s resignation, limiting the powers of his anointed successor, Kassym-Jomart Tokayev. How long can Tokayev credibly remain president considering such a transparent undermining of his authority? Is Nazarbayev, in fact, grooming his daughter, Dariga Nazarbayeva, another relative or a power player from outside the family for the leadership in the longer term? Will the ‘Kazakh tandem’ of Nazarbayev and Tokayev function effectively, or will tensions and conflicts arise between them as many claim is happening already? How will the leadership cope with the protest mood now manifest on the streets of Kazakhstan, and address the political and socio-economic grievances fuelling this discontent? How might the political transition play out if Nazarbayev were to suddenly exit the political scene altogether?And what is the long-term transition plan for the time when Nazarbayev has departed, and how effective will it be?As Kazakhstan enters uncharted territory, the purpose of this report is twofold. First, to make the case for the West to devote more attention to Kazakhstan. The country’s relative importance in Central Asia, and as the constant focus of intense attention from China and Russia, suggests that the West is wrong to direct so little time and diplomatic effort and so few resources towards it. This is not so much a miscalculation (that would be to assume there had been a calculation in the first place) as a misstep through neglect, presupposing that the future will resemble the present – with Kazakhstan remaining stable internally, relatively inconsequential geopolitically but nevertheless a friendly ally to the West. In fact, the country’s trajectory over the next few years is of potentially strategic import. This is because even its political semi-transition presents the West with a rare opportunity to push back against the global rise of authoritarianism, in a state that is open to rational argument and economic logic.The second function of the report is to serve as a well-intentioned message to the leadership of Kazakhstan. The research undertaken by the report’s eight authors shows that Kazakhstan is at risk of failing to achieve the goals its leadership has set for the country. As significant as it has been, the partial stepping aside of Nazarbayev by no means guarantees the modernization and renewal that he and his successor have promised. Far deeper political, economic and social reforms will be needed if Kazakhstan is to meet the growing challenges to its stability, prosperity and development. Street protests since Nazarbayev’s resignation have demonstrated a level of popular disaffection far higher than the authorities acknowledge. The leadership needs to bridge the disconnect between the rulers and the ruled and start listening to its people.To avoid slipping into decline, and to resist external pressures and geopolitical overtures that could diminish the sovereignty that its leadership is so determined to safeguard, Kazakhstan needs new faces – innovators and reformers – throughout every level of the administration, as well as new ideas. This report is intended to help with the ‘ideas’ part of that proposition. It also includes a series of recommendations for Western governments and institutions and for the Kazakhstan government. Department/project Russia and Eurasia Programme, Internal Dynamics and External Interests in Central Asia Full Article
tan Kazakhstan: Reaching Out to Central Asian Neighbours By feedproxy.google.com Published On :: Wed, 04 Dec 2019 10:21:03 +0000 4 December 2019 Annette Bohr Associate Fellow, Russia and Eurasia Programme Despite its regional outreach, Kazakhstan’s diplomatic priority will remain Russia, China, and Europe. 2019-12-04-Kaz.jpg Kazakhstan's President Kassym-Jomart Tokayev, Kazakh Majilis Chairman Nurlan Nigmatulin and ex-president Nursultan Nazarbayev at an inauguration ceremony in parliament. Photo: Pavel AleksandrovTASS via Getty Images. Leaders of the resource-rich Central Asian region have the propensity to remain in power until mortality dictates otherwise. Much like the UK and Brexit, however, few wanted to see Central Asia’s longest reigning ruler, Kazakhstan’s septuagenarian president Nursultan Nazarbayev, crash out without a deal.The sudden departure of the country’s official leader of the nation with no clear succession plan could have led to investment chaos, intra-elite fighting and the unravelling in a matter of months of a system he had built over decades, à la Uzbekistan following the death of long-serving autocrat Islam Karimov in 2016.In order to avoid just such a ‘no-deal’ scenario and ensure the continuity of his policies, in March Nazarbayev carefully choreographed his own resignation and the election of a hand-picked successor, President Kassym-Jomart Tokayev, while retaining plum positions and powers for himself.Tokayev’s assumption of the presidency was accompanied by protesters in the streets, increasing wealth inequality, rising Sinophobia among rank-and-file Kazakhstanis, a hard-to-kick economic dependence on oil revenues and a lack of clarity as to which leader—the old or the new president—would actually be calling the shots. But, amidst this plethora of concerns, as argued in a recent Chatham House report, Kazakhstan: Tested by Transition, one bright spot has been the tangible growth of intra-Central Asian cooperation, with the Nazarbayev-Tokayev ruling duo appearing eager to improve the regional dialogue.Kazakhstan has long shaped its identity as a Eurasian state that has acted as more of an intermediary between Russia and Central Asia than as an integral part of the Central Asian region. But since 2017, in particular, Kazakhstan has been increasingly looking for opportunities to boost hitherto weak cooperation with its Central Asian neighbours. While this is first and foremost owing to the liberalization of Uzbekistan’s large market, there are other factors at work that get less airplay.One such factor is a perceptible disentangling from the Kremlin’s policy directions as Kazakhstan has come to view Russia’s foreign policy as increasingly neo-colonial. The example of the Russia-led Eurasian Economic Union is in many respects more off-putting than inspiring, and Nur-Sultan does not want to be locked tightly into the union’s economic orbit. And in distancing itself slightly from Moscow in order to limit Russian leverage in its affairs, Nur-Sultan has shown itself to be more open to Central Asian regional initiatives.As part of the leadership’s plan to offset oil dependence, Kazakhstan aspires to become the transport, telecommunications and investment hub for Eurasian integration. The intense focus on connectivity and the development of logistical arteries and infrastructure could have the knock-on effect of boosting trade within the Central Asian region and reducing transit times, which are currently greater than in most other parts of the globe.In addition, demographic trends and educational shifts that favour ethnic Kazakhs, together with a growing ethno-nationalist narrative, have allowed the state’s leadership to identify more closely with Kazakhstan’s common Central Asian heritage and, by extension, a common Central Asian region—although Kazakhstan’s leadership still remains eager to demonstrate that the country is not just another ‘stan’. The coming to power of President Mirziyoyev in Uzbekistan appears to have made Kazakhstan more aware of the interconnectedness of the two countries in terms of geographical location and potential economic complementarities, as well as culture and history.Not least, there is a growing recognition among the Central Asian states themselves—including isolationist Turkmenistan to a degree—that deepening regional trade is mutually beneficial, especially given the constraints associated with Russia’s economic problems. The strengthening of Kazakhstan’s ties with Uzbekistan has slowly kick-started regional cooperation as a whole: trade turnover between the Central Asian states in 2018 grew by 35 per cent on the previous year.But both Kazakhstan and Uzbekistan are keen to stress that there is no discussion of integration or institutionalization, not least because previous attempts at integration have been overtaken by Russia, leaving Central Asia without its own coordinating body.The official consensus in Kazakhstan is that Uzbekistan’s economic reforms after years of isolation will spur ‘a healthy rivalry’ and ultimately boost Kazakhstan’s own economy, in so far as the competition for foreign investment will require both countries to work harder to improve their respective business and regulatory environments.At the unofficial level, however, some Kazakhstani analysts view Uzbekistan’s rise as potentially unprofitable, given the possible diversion of some investments and market activity from Kazakhstan to Uzbekistan. Moreover, Uzbekistan has the advantage of having undergone a clear change of executive, while it remains unclear which developments await Kazakhstan once First President Nazarbayev leaves the scene for good.It can certainly be argued that Uzbekistan does pose a potential threat in the long-term to Kazakhstan’s entrenched position as Central Asia’s economic powerhouse: Uzbekistan’s population is one-and-a-half times bigger, even if its nominal GDP is three times smaller. Uzbekistan has a bigger market and a well-developed industrial sector, and is already the regional leader in terms of security. But it is not as though the world’s interest is moving from Kazakhstan to Uzbekistan; rather, Uzbekistan is in the process of trying to catch up.Despite this relatively upbeat picture, Kazakhstan’s combined trade with the other Central Asian states accounts for less than 5 per cent of its total volume of foreign trade—a figure that cannot begin to equal its trade with Russia, China, and Europe. As a result, Kazakhstan will continue to give greater importance to positioning itself as a global player than as a regional leader.This article was originally published in The Diplomat. Full Article
tan In a COVID-19 World, Russia Sticks to International Distancing By feedproxy.google.com Published On :: Sun, 29 Mar 2020 20:49:14 +0000 29 March 2020 Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world. 2020-03-29-Coronavirus-Russia-Moscow Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images. Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.Russian trolls never sleepRussia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.Self-isolation, Kremlin styleMeanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia. Full Article
tan Leaving Afghanistan By kolembo.wordpress.com Published On :: Wed, 12 Nov 2014 20:38:20 +0000 I am the gate keeper. Two flags gone Marking bodies where they fell, Manure, Useful, Two flags fleeing loose rounds, Auras, Fleeting, Bring your palm, I can read it now, Unhinged as I am, The last are, Making their way home. -evocative short poetry- Full Article Poetry
tan Standing Behind People By kolembo.wordpress.com Published On :: Mon, 26 Jun 2017 13:28:26 +0000 You are the, Reduction, Sweet wine, the Product of every, Human Being, Behind you, and That is all; Behind every, Great human, is God, Behind every great, Man, a woman A woman, a man, A man, a man and, A woman, a woman, you Are the original ancestor, You. ♦Picture – 500Px♦ -short […] Full Article Poetry god religion Self
tan Donovan Stanberry | Revisiting food security amidst COVID-19 pandemic By jamaica-gleaner.com Published On :: Sun, 29 Mar 2020 00:22:28 -0500 Between December 2019 and February 2020, The Gleaner published a series of articles on my behalf, exploring the issue of food security in Jamaica based on an analysis of the country’s food-import bill for 2018. The current COVID-19 pandemic, which... Full Article
tan Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice By diabetes.diabetesjournals.org Published On :: 2020-01-20T12:00:25-08:00 Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcrm–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcrm–/m– mice than in control Hmgcrfl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm–/m– and Hmgcrfl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity. Full Article
tan Netanyahu gets backing to form new gov’t By jamaica-gleaner.com Published On :: Fri, 08 May 2020 00:19:08 -0500 JERUSALEM (AP): Israeli Prime Minister Benjamin Netanyahu formally received the support of a majority of lawmakers to lead a new government yesterday, paving the way for a controversial power-sharing deal with rival-turned-partner Benny Gantz.... Full Article
tan Katherine Henderson A and E consultant - lack of ward beds is hitting A and E the hardest By feeds.bmj.com Published On :: Wed, 11 Mar 2015 14:55:57 +0000 Katherine Henderson is the clinical lead of the emergency department at St Thomas's hospital in London. She worries that lack of ward space is having a domino effect throughout A and E and is the cause of increased waiting time for both patients and ambulances. If you would like to contribute to this collection, please email a brief audio... Full Article
tan Is place of death important to patients? By feeds.bmj.com Published On :: Mon, 12 Oct 2015 13:41:39 +0000 The current orthodoxy is that home is the best and preferred place of death for most people, but in this podcast, Kristian Pollock a sociologist from Nottingham University questions these assumptions and calls for greater attention to improving the experience of dying in hospital and elsewhere. Read the full... Full Article
tan What's going on with life expectancy? By feeds.bmj.com Published On :: Fri, 21 Jul 2017 13:35:10 +0000 The increase in life expectancy in England has almost “ground to a halt” since 2010 and austerity measures are likely to be a significant contributor. In this podcast Michael Marmot, director at University College London’s Institute of Health Equity, joins us to discuss what might be causing that drop off, and why a decrease in early life chances... Full Article
tan Nutritional science - Is quality more important than quantity? By feeds.bmj.com Published On :: Fri, 07 Sep 2018 17:39:13 +0000 We at The BMJ care about food, and if our listener stats are to be believed, so do you. In this podcast we’re looking at quality as an important driver of a good diet. At our recent food conference - Food For Thought - hosted in Zurich by Swiss Re we brought researchers in many fields of nutritional science together. We asked people with... Full Article
tan UK children are drinking less and the importance of a publicly provided NHS By feeds.bmj.com Published On :: Fri, 28 Sep 2018 18:36:43 +0000 Brits have a reputation as Europe’s boozers - and for good reason, with alcohol consumption higher than much of the rest of the continent. That reputation is extended to our young people too - but is it still deserved? Joanna Inchley, senior research fellow at the University of St Andrews, explains new research on decreasing drinking -... Full Article
tan Diabetes Insipidus - the danger of misunderstanding diabetes By feeds.bmj.com Published On :: Fri, 01 Mar 2019 18:10:43 +0000 Diabetes is synonymous with sugar, but diabetes insipidus, "water diabetes", can't be forgotten. Between 2009 and 2016, 4 people died in hospital in England, when lifesaving treatment for the condition was not given. In this podcast, we hear some practical tips for non-specialists to aid diagnosis, and how patients should be managed during... Full Article
tan Big Tan - Is the sunbed industry targeting research? By feeds.bmj.com Published On :: Mon, 10 Feb 2020 17:42:30 +0000 In 2012, Eleni Linos, professor of dermatology at Stanford university, published a systematic review and meta-analysis of the link between non-melanoma cancer and sun-beds. That bit of pretty standard research, and a particular rapid response to it, has kicked of years of work - and in this podcast I talk to Eleni and her colleagues Stanton... Full Article
tan Prospective Analysis of The Insulin-Resistance Syndrome (Syndrome X) By diabetes.diabetesjournals.org Published On :: 1992-06-01 Steven M HaffnerJun 1, 1992; 41:715-722Original Article Full Article
tan Fuel selection in human skeletal muscle in insulin resistance: a reexamination By diabetes.diabetesjournals.org Published On :: 2000-05-01 DE KelleyMay 1, 2000; 49:677-683Articles Full Article
tan Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes By diabetes.diabetesjournals.org Published On :: 1996-12-01 Alan R SaltielDec 1, 1996; 45:1661-1669Perspectives in Diabetes Full Article
tan Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents By diabetes.diabetesjournals.org Published On :: 1999-08-01 G PerseghinAug 1, 1999; 48:1600-1606Articles Full Article
tan Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance By diabetes.diabetesjournals.org Published On :: 1992-03-01 Eve Van CauterMar 1, 1992; 41:368-377Original Article Full Article
tan Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha} By diabetes.diabetesjournals.org Published On :: 2002-07-01 Samar I. ItaniJul 1, 2002; 51:2005-2011Rapid Publications Full Article
tan Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study By diabetes.diabetesjournals.org Published On :: 2002-04-01 Andreas FestaApr 1, 2002; 51:1131-1137Complications Full Article
tan Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women By diabetes.diabetesjournals.org Published On :: 2002-09-01 Thomas A. BuchananSep 1, 2002; 51:2796-2803Pathophysiology Full Article