ind The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining {alpha}-tubulin acetylation [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment. Full Article
ind 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
ind Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice By diabetes.diabetesjournals.org Published On :: 2008-06-01 Patrice D. CaniJun 1, 2008; 57:1470-1481Metabolism Full Article
ind PPARA Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid By diabetes.diabetesjournals.org Published On :: 2020-04-01 Mario Luca MorieriApr 1, 2020; 69:771-783Genetics/Genomes/Proteomics/Metabolomics Full Article
ind 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
ind Transparency and independence in the vetting and recommendation of vaccine products By feeds.bmj.com Published On :: Friday, May 8, 2020 - 10:40 Full Article
ind US adults are more likely to have poor health than those in 10 similar countries, survey finds By feeds.bmj.com Published On :: Wednesday, November 16, 2016 - 22:00 Full Article
ind Zika related microcephaly may appear after birth, study finds By feeds.bmj.com Published On :: Wednesday, November 23, 2016 - 14:06 Full Article
ind Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis By feeds.bmj.com Published On :: Monday, December 5, 2016 - 14:46 Full Article
ind Dr Lindsay Newman By feedproxy.google.com Published On :: Fri, 20 Sep 2019 12:15:09 +0000 Senior Research Fellow, US and the Americas Programme Biography Dr Lindsay Newman is senior research fellow in the US and Americas Programme. She was previously head of political risk (2019) and principal research analyst (2014-2018) at IHS Markit where she worked as part of the country risk and forecasting team, focusing on its global risk practice as well as North American analysis.Prior to IHS Markit, Lindsay worked as a lawyer in the capital markets practice group of White & Case, an international law firm.She writes and speaks on a range of US domestic and foreign policy topics including US-China trade negotiations, transatlantic relations, US agenda in the Middle East, terrorism and political violence, elections, legislative politics and immigration.She received her BA from Yale University (Political Science and International Studies, magna cum laude), Juris Doctor from New York University School of Law and PhD from the Politics Department at New York University. Areas of expertise Elections and electoral processesUS domestic politicsUS foreign policyLegal institutionsPolitical risk Past experience 2019Associate director, head of political risk, IHS Markit2014-18Principal research analyst, IHS Markit2010-11Assistant instructor, NYU Abu Dhabi Sheikh Mohamed bin Zayed ScholarsProgramme2004-07Lawyer, White & Case LLP Email @lindsayrsnewman LinkedIn Full Article
ind Legal Provision for Crisis Preparedness: Foresight not Hindsight By feedproxy.google.com Published On :: Tue, 21 Apr 2020 17:03:31 +0000 21 April 2020 Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary COVID-19 is proving to be a grave threat to humanity. But this is not a one-off, there will be future crises, and we can be better prepared to mitigate them. 2020-04-21-Nurse-COVID-Test Examining a patient while testing for COVID-19 at the Velocity Urgent Care in Woodbridge, Virginia. Photo by Chip Somodevilla/Getty Images. A controversial debate during COVID-19 is the state of readiness within governments and health systems for a pandemic, with lines of the debate drawn on the issues of testing provision, personal protective equipment (PPE), and the speed of decision-making.President Macron in a speech to the nation admitted French medical workers did not have enough PPE and that mistakes had been made: ‘Were we prepared for this crisis? We have to say that no, we weren’t, but we have to admit our errors … and we will learn from this’.In reality few governments were fully prepared. In years to come, all will ask: ‘how could we have been better prepared, what did we do wrong, and what can we learn?’. But after every crisis, governments ask these same questions.Most countries have put in place national risk assessments and established processes and systems to monitor and stress-test crisis-preparedness. So why have some countries been seemingly better prepared?Comparing different approachesSome have had more time and been able to watch the spread of the disease and learn from those countries that had it first. Others have taken their own routes, and there will be much to learn from comparing these different approaches in the longer run.Governments in Asia have been strongly influenced by the experience of the SARS epidemic in 2002-3 and - South Korea in particular - the MERS-CoV outbreak in 2015 which was the largest outside the Middle East. Several carried out preparatory work in terms of risk assessment, preparedness measures and resilience planning for a wide range of threats.Case Study of Preparedness: South KoreaBy 2007, South Korea had established the Division of Public Health Crisis Response in Korea Centers for Disease Control and Prevention (KCDC) and, in 2016, the KCDC Center for Public Health Emergency Preparedness and Response had established a round-the-clock Emergency Operations Center with rapid response teams.KCDC is responsible for the distribution of antiviral stockpiles to 16 cities and provinces that are required by law to hold and manage antiviral stockpiles.And, at the international level, there are frameworks for preparedness for pandemics. The International Health Regulations (IHR) - adopted at the 2005 World Health Assembly and binding on member states - require countries to report certain disease outbreaks and public health events to the World Health Organization (WHO) and ‘prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade’.Under IHR, governments committed to a programme of building core capacities including coordination, surveillance, response and preparedness. The UN Sendai Framework for Disaster Risk highlights disaster preparedness for effective response as one of its main purposes and has already incorporated these measures into the Sustainable Development Goals (SDGs) and other Agenda 2030 initiatives. UN Secretary-General António Guterres has said COVID-19 ‘poses a significant threat to the maintenance of international peace and security’ and that ‘a signal of unity and resolve from the Council would count for a lot at this anxious time’.Case Study of Preparedness: United StatesThe National Institutes of Health (NIH) and the Center for Disease Control (CDC) established PERRC – the Preparedness for Emergency Response Research Centers - as a requirement of the 2006 Pandemic and All-Hazards Preparedness Act, which required research to ‘improve federal, state, local, and tribal public health preparedness and response systems’.The 2006 Act has since been supplanted by the 2019 Pandemic and All-Hazards Preparedness and Advancing Innovation Act. This created the post of Assistant Secretary for Preparedness and Response (ASPR) in the Department for Health and Human Services (HHS) and authorised the development and acquisitions of medical countermeasures and a quadrennial National Health Security Strategy.The 2019 Act also set in place a number of measures including the requirement for the US government to re-evaluate several important metrics of the Public Health Emergency Preparedness cooperative agreement and the Hospital Preparedness Program, and a requirement for a report on the states of preparedness and response in US healthcare facilities.This pandemic looks set to continue to be a grave threat to humanity. But there will also be future pandemics – whether another type of coronavirus or a new influenza virus – and our species will be threatened again, we just don’t know when.Other disasters too will befall us – we already see the impacts of climate change arriving on our doorsteps characterised by increased numbers and intensity of floods, hurricanes, fires, crop failure and other manifestations of a warming, increasingly turbulent atmosphere and we will continue to suffer major volcanic eruptions, earthquakes and tsunamis. All high impact, unknown probability events.Preparedness for an unknown future is expensive and requires a great deal of effort for events that may not happen within the preparers’ lifetimes. It is hard to imagine now, but people will forget this crisis, and revert to their imagined projections of the future where crises don’t occur, and progress follows progress. But history shows us otherwise.Preparations for future crises always fall prey to financial cuts and austerity measures in lean times unless there is a mechanism to prevent that. Cost-benefit analyses will understandably tend to prioritise the urgent over the long-term. So governments should put in place legislation – or strengthen existing legislation – now to ensure their countries are as prepared as possible for whatever crisis is coming.Such a legal requirement would require governments to report back to parliament every year on the state of their national preparations detailing such measures as:The exact levels of stocks of essential materials (including medical equipment)The ability of hospitals to cope with large influx of patientsHow many drills, exercises and simulations had been organised – and their findingsWhat was being done to implement lessons learned & improve preparednessIn addition, further actions should be taken:Parliamentary committees such as the UK Joint Committee on the National Security Strategy should scrutinise the government’s readiness for the potential threats outlined in the National Risk register for Civil Emergencies in-depth on an annual basis.Parliamentarians, including ministers, with responsibility for national security and resilience should participate in drills, table-top exercises and simulations to see for themselves the problems inherent with dealing with crises.All governments should have a minister (or equivalent) with the sole responsibility for national crisis preparedness and resilience. The Minister would be empowered to liaise internationally and coordinate local responses such as local resilience groups.There should be ring-fenced budget lines in annual budgets specifically for preparedness and resilience measures, annually reported on and assessed by parliaments as part of the due diligence process.And at the international level:The UN Security Council should establish a Crisis Preparedness Committee to bolster the ability of United Nations Member States to respond to international crisis such as pandemics, within their borders and across regions. The Committee would function in a similar fashion as the Counter Terrorism Committee that was established following the 9/11 terrorist attacks in the United States.States should present reports on their level of preparedness to the UN Security Council. The Crisis Preparedness Committee could establish a group of experts who would conduct expert assessments of each member state’s risks and preparedness and facilitate technical assistance as required.Regional bodies such as the OSCE, ASEAN and ARF, the AU, the OAS, the PIF etc could also request national reports on crisis preparedness for discussion and cooperation at the regional level.COVID-19 has been referred to as the 9/11 of crisis preparedness and response. Just as that shocking terrorist attack shifted the world and created a series of measures to address terrorism, we now recognise our security frameworks need far more emphasis on being prepared and being resilient. Whatever has been done in the past, it is clear that was nowhere near enough and that has to change.Case Study of Preparedness: The UKThe National Risk Register was first published in 2008 as part of the undertakings laid out in the National Security Strategy (the UK also published the Biological Security Strategy in July 2018). Now entitled the National Risk Register for Civil Emergencies it has been updated regularly to analyse the risks of major emergencies that could affect the UK in the next five years and provide resilience advice and guidance.The latest edition - produced in 2017 when the UK had a Minister for Government Resilience and Efficiency - placed the risk of a pandemic influenza in the ‘highly likely and most severe’ category. It stood out from all the other identified risks, whereas an emerging disease (such as COVID-19) was identified as ‘highly likely but with moderate impact’.However, much preparatory work for an influenza pandemic is the same as for COVID-19, particularly in prepositioning large stocks of PPE, readiness within large hospitals, and the creation of new hospitals and facilities.One key issue is that the 2017 NHS Operating Framework for Managing the Response to Pandemic Influenza was dependent on pre-positioned ’just in case’ stockpiles of PPE. But as it became clear the PPE stocks were not adequate for the pandemic, it was reported that recommendations about the stockpile by NERVTAG (the New and Emerging Respiratory Virus Threats Advisory Group which advises the government on the threat posed by new and emerging respiratory viruses) had been subjected to an ‘economic assessment’ and decisions reversed on, for example, eye protection.The UK chief medical officer Dame Sally Davies, when speaking at the World Health Organization about Operation Cygnus – a 2016 three-day exercise on a flu pandemic in the UK – reportedly said the UK was not ready for a severe flu attack and ‘a lot of things need improving’.Aware of the significance of the situation, the UK Parliamentary Joint Committee on the National Security Strategy launched an inquiry in 2019 on ‘Biosecurity and human health: preparing for emerging infectious diseases and bioweapons’ which intended to coordinate a cross-government approach to biosecurity threats. But the inquiry had to postpone its oral hearings scheduled for late October 2019 and, because of the general election in December 2019, the committee was obliged to close the inquiry. Full Article
ind Current Index to Statistics By blogs.ams.org Published On :: Fri, 07 Feb 2020 20:13:21 +0000 The Current Index to Statistics (CIS) is now hosted by the AMS. It is available on the MathSciNet servers from the URL mathscinet.ams.org/cis. The database is openly available using a brand new search interface. Some history The Current Index to … Continue reading → Full Article Announcements Extra content New features
ind 'The Truth is, Chile is Unequal': What's Behind Chile's Protests By feedproxy.google.com Published On :: Tue, 17 Dec 2019 19:33:39 +0000 18 December 2019 Dr Christopher Sabatini Senior Research Fellow for Latin America, US and the Americas Programme @ChrisSabatini LinkedIn Lyndsey Jefferson Digital Editor, Communications and Publishing Department @LyndseyLdn As part of a series on global protests, Dr Christopher Sabatini tells Lyndsey Jefferson why Chileans are taking to the streets. GettyImages-1177498531.jpg A demonstrator waves a Chilean flag during a protest in Santiago on 21 October 2019. Photo: Getty Images. Why are these protests happening now?The truth is, Chile is unequal, even though it actually reduced poverty from 1989, the time of the democratic transition, until today, from 40% to 16%.There are a number of reasons for the protests. One is the most proximate cause, which is the increase in the subway fares, but that really doesn’t explain the underlying tensions.One of those tensions is despite reductions in poverty, social mobility remains a large problem in Chile. It remains a very elitist country with limited social mobility. So, poverty may be reduced, but the likelihood that someone in the working middle class would reach the upper middle class has always been a stretch.The second issue is a lack of political change. The last four presidents were the same two people.Chile’s been governed, with the exception of Piñera, basically by the same political coalition, La Concertación, which is a combination of the Christian Democratic and Socialist parties. Piñera came from the right, an outside party, but even he has remained. There has been no renewal of the political leadership which again reinforces that lack of social mobility. Do the protesters have any other demands or grievances? The demands are amorphous and that’s part of the issue – they’re going to be difficult to meet. People are expressing a genuine desire for change but what would that change mean?Chileans don’t necessarily want to change the economic model; they simply want more mobility. That’s difficult to do and these are untested demands. Chileans also want political reform. What Piñera offered is to rewrite the constitution, which was created under military government in 1980. Other than some changes here and there in terms of the electoral system and reduction of military power, it has pretty much remained intact.Will constitutional change really address these demands? It’s simply a document that may create the rules for how power is allocated and conducted, but it’s not going to dramatically remake Chilean society.You mentioned inequality as a key driver of the protests. Can you expand a bit more on the current economic situation of ordinary Chileans?Chile is going to grow at only around 2-3%, but it was growing at around 4-5% earlier. A lot of those funds were ploughed into social programmes that have since been reduced. Chile’s economy really boomed in the early 2000s because of Chinese demands of Chilean imports. But as with any sort of commodities-based economy, the jobs it provides tend to be lower wage.As a result, despite the fact that Chile tried to diversify its economy by investing in entrepreneurship and innovation, it hasn’t grown in a way that provides jobs that many associate with upward mobility. As Chile's economy cooled, its ability to lift people out of poverty lagged as well. Demonstrators hold placards depicting eyes – in reference to police pellets hitting demonstrators' eyes – during a protest in Santiago on 10 December 2019. Photo: Getty Images. Two major issues for the protesters are education and pensions – can you explain why this is?These are two issues of the economic and social model that was held up at one time as being a model for the region, the neoliberal models that are really coming under question and are in some ways at the heart of this.One is the privatized pension system which is failing to produce the returns that retirees need to survive. The second is the education system. Chile created a voucher system where parents can shop around and send their kids to the best schools. The idea was to create competition among schools to improve.The problem was like any market, it created a certain amount of inequality among schools. There was a problem of some schools underperforming and being relegated poorer performing students, or students being forced to go to those schools because the more successful schools were already spoken for. At the end of October, the government announced a series of social reforms. Will this be enough to satisfy the protesters’ demands?Social reforms may address some of the issues of insufficient pensions or lack of quality education, but it will take a while for them to have an effect.The second thing is, social reforms don’t address the issues of power. At the heart of this is this idea of closed economic, political and social power. That comes about through economic growth and how you break up concentrations of wealth. Social reforms aren’t going to do that, although they’ll help on the margins. We’re seeing horrific scenes of police violence against protesters and dozens of people have died. Has this deterred the protesters in any way? No, in many ways it has sort of inspired them. It has, I think, sustained the protests.We’re not talking massive repression and tanks rolling in like Tiananmen Square. We’re talking about tear gas, rubber bullets, some injuries and deaths, and even credible reports of torture.It’s funny you should mention this – a class I’m teaching today is about social media and protests. One of the central arguments is that successful social protests need a martyr; they need a rallying cry.The deaths and the repression sort of help sustain that, but moreover, social media helps communicate what’s happening through videos and pictures. It really helps maintain this sense of righteousness, disdain for the government, and this idea of the need to demand change.Where do you see this going next?I don’t think we know. In the 60s and 70s, the political scientist Samuel Huntington argued in Political Order in Changing Societies that as economies grow, political institutions often strain to contain and channel demands. I think we’re seeing this now.This social ferment over political, economic and social demands is uncharted water. I don’t know where this will go, but I think we’ll see a change in the constitution. We’ve already seen a fragmenting of the party system, which I think will continue. Hopefully, that will lead to new leadership that can help reflect a change in Chile itself. Full Article
ind Cheapest Web Hosting India By investing.96.lt Published On :: Fri, 20 Jan 2017 07:45:05 UTC If you have lack of knowledge about web hosting, then you ,must read this blog, here you will get every detailed information regarding the web hosting , Linux hosting or windows hosting. You can find best up to your knowledge here, all about cheap web hosting is mentioned and how to find best and cheapest hosting plans according to your needs. Full Article Computer and Technology
ind Covid-19: Doctors face shortages of vital drugs, gases, and therapeutics, survey finds By feeds.bmj.com Published On :: Monday, May 4, 2020 - 16:36 Full Article
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ind Windrush Film Festival to feature young talent By jamaica-gleaner.com Published On :: Sat, 09 May 2020 00:09:06 -0500 Emerging film-makers will have the opportunity to produce a short film based on the theme ‘My Windrush Story – What Windrush Means to Me’ as part of the Windrush Caribbean Film Festival (WCFF), which will be held later this year as part of Black... Full Article
ind Zelenskyy Finds That There Are No Easy Solutions in Donbas By feedproxy.google.com Published On :: Wed, 23 Oct 2019 14:46:36 +0000 23 October 2019 Duncan Allan Associate Fellow, Russia and Eurasia Programme Leo Litra Senior Research Fellow, New Europe Center The president has attempted to use the so-called Steinmeier Formula to find a compromise on holding elections in the east of Ukraine. But he has run into a stark reality: Moscow and Kyiv’s interests remain irreconcilable. 2019-10-23-Ukraine.jpg A banner reading 'No capitulation!' is unfurled above the entrance to the city hall in Kyiv as part of protests against implementation of the so-called Steinmeier Formula. Photo: Getty Images. In 2016, the then-German foreign minister, Frank-Walter Steinmeier, suggested a way around the impasse in east Ukraine.He proposed that elections in the areas held by Russian-backed insurgents – the ‘Donetsk People’s Republic’ (DNR) and the ‘Luhansk People’s Republic’ (LNR) – could be held under Ukrainian legislation, with Kyiv adopting a temporary law on ‘special status’, the main disagreement between Russia and Ukraine in the Minsk Agreements. This law would become permanent once the Organization for Security and Cooperation in Europe (OSCE) had declared that elections correspond with OSCE standards.The reaction in Ukraine was strongly negative. The so-called Steinmeier Formula contradicted Kyiv’s position that elections in the occupied Donbas should only go ahead in a secure environment – requiring the prior withdrawal of Russian forces and the return of the eastern border to Ukraine’s control. It also did not address the differing views of ‘special status’; Russia demands a much greater devolution of constitutional powers to the DNR and LNR regimes than Ukraine will grant.But on 1 October, Volodymyr Zelenskyy, the new Ukrainian president, announced that he was signing up to the Steinmeier Formula. He also announced a conditional withdrawal of Ukrainian forces from two frontline areas in the east.Quick reversalDuring the 2019 presidential election campaign, Zelenskyy repeatedly promised that, if elected, he would re-energize efforts to end the war. This appealed to many Ukrainians, who understandably want the conflict over, although Zelenskyy’s eventual electoral victory was largely won on domestic issues.But his initiative quickly ran into two problems.First, following a major prisoner swap in September, Russian President Vladimir Putin appeared to judge that Zelenskyy was in a hurry to deliver his election promises and was acting without consulting France and Germany. Russia had earlier demanded that Ukraine formally agree to elections in the Donbas as the precondition for a summit of the ‘Normandy’ powers (the diplomatic format comprising leaders of Ukraine, Russia, Germany and France, which has not met since 2016).Moreover, the US, which is not part of the ‘Normandy’ group, has seemed disengaged because of domestic controversies. Concluding that Zelenskyy was vulnerable, the Kremlin welcomed his announcement about the Steinmeier Formula but declined to assent to a summit, hoping to extract further concessions.Second, Zelenskyy’s action triggered protests in Kyiv and other Ukrainian cities. Critics feared that he intended to make unilateral concessions over ‘special status’. Though he tried to assure Ukrainians that ‘there won't be any elections there if the [Russian] troops are still there’, concerns were fuelled by what many saw as his lack of openness about what the Steinmeier Formula really meant. Ukrainian public opinion wants an end to the war, but apparently not at any price.Zelenskyy duly rowed back. During a marathon 14-hour press conference on 10 October, he emphasized that he would not surrender Ukraine’s vital interests. He also acknowledged that he had been insufficiently open with the Ukrainian public. For the time being at least, he seems to have been given pause.A situation resistant to compromiseInstead, Zelenskyy may now attempt to ‘freeze’ the conflict by ending active operations. This is not Ukraine’s favoured outcome but could be the most realistic one in current conditions. Russia still calculates that time is on its side. It believes that Western support for Ukraine is lukewarm and that Kyiv will eventually have to give it what it wants. Russia clearly felt no pressure to respond positively to Zelenskyy’s overture, which it probably read as a weakness to be exploited. For these reasons, Zelenskyy now appears less optimistic that rapid progress to end the war is possible. A new summit of the ‘Normandy’ powers may happen but looks unlikely in the near future. This may act as an incentive for further bilateral negotiations between Ukraine and Russia, such as those which delivered the prisoner swap. However, a diplomatic process managed by Zelenskyy and Putin alone risks reducing Ukraine’s leverage. Finally, the main obstacles to implementation of the Minsk Agreements – radically different views of elections in, and ‘special status’ for, the DNR and LNR – remain. The Kremlin’s versions of both would gravely limit Ukraine’s sovereignty; Kyiv’s would facilitate the re-establishment of its control over the east. It is hard to see how this gap can be bridged.Tellingly, the Steinmeier Formula offers no answer to this conundrum. Some conflicts, it seems, are resistant to diplomatic compromises that aim to satisfy everyone equally. Full Article
ind The New Orthodox Church of Ukraine: Opportunities and Challenges of Canonical Independence By feedproxy.google.com Published On :: Wed, 18 Dec 2019 09:55:01 +0000 Invitation Only Research Event 22 January 2020 - 10:00am to 11:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Archbishop Yevstraty (Zoria) of Chernihiv, Deputy Head of Department for External Church Relations, Ukrainian Orthodox Church (Orthodox Church of Ukraine) In January 2019, the Ecumenical Patriarchate of Constantinople granted the Orthodox Church of Ukraine a self-governing status, ending its centuries-long subordination to the Moscow Patriarchate. The Russian Orthodox Church condemned this decision and severed its links with the Constantinople Patriarchate.More than 500 parishes have left the Ukrainian Orthodox Church of the Moscow Patriarchate to join the newly independent Ukrainian Orthodox Church (UOC).What challenges is the new church facing? Has its independence been recognized by other Orthodox churches? How is it affected by the schism between Constantinople and Moscow? What are UOC’s priorities in relations with the West and with the Orthodox world? Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
ind We are leaving them behind By kolembo.wordpress.com Published On :: Fri, 13 Jun 2014 08:45:10 +0000 Never mind steel, We are creating new materials, Carbon nano-tubes, poly-ceramics, Twirl a ball above your head, we are Building elevators into space, Stringing massage parlours around the earth, We are engineering ourselves, Computer worlds and, Selling real estate, we Are leaving the old people, Behind, Stained curtains and they are, Walking into forests, […] Full Article Poetry age displacement japan poetry technology
ind Loosing our minds By kolembo.wordpress.com Published On :: Fri, 05 Feb 2016 03:28:35 +0000 I am right. You may say that I am not, but I have, Demanded love and, You, Are wrong. Black and blue and red hummingbird, I Know what I am saying, you Left the kids again, And we argue, Tall as bamboo we, Kill each other, Taking long hours to, Identify precisely who left […] Full Article Poetry age alzheimers family forgiveness poetry relationship Righteousness Sacrifice
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ind Home – Race in India By kolembo.wordpress.com Published On :: Wed, 07 Jun 2017 05:17:10 +0000 The idea of home is so complicated to me; home isn’t here people look at me like I am from somewhere else. Where is home? Writing became an expression of my discomfort a language an arrangement of unbroken rage writing poetry to question why? Poetry to reclaim my identity and to be home again. My […] Full Article Poetry
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ind CRM Software in India By investing.96.lt Published On :: Sat, 03 Aug 2019 06:18:47 UTC SalesFundaa, top leading CRM Software Development Company in India. Our CRM Software Features is Activity Management, Alerts, Notifications, Analytics, Reporting, Billing, Invoicing, Calendar Management, Contact Management, Customer Information System, Social media management, Tasks and Deals. Full Article News
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ind Jamaican musician finds fulfilment while stuck in Bali By jamaica-gleaner.com Published On :: Tue, 05 May 2020 00:07:15 -0500 LOCAL MUSICIAN Janine JKUHL’s two-month-long immersive creative residency programme in Bali, Indonesia, has been extended indefinitely, or at least until the world has the COVID-19 spread under control and international airports open up to... Full Article
ind India Travel, Trip to India, Tour to India, Travel to India By investing.96.lt Published On :: Thu, 16 Jun 2016 05:02:54 UTC We are Delhi India based India Tour Operator and Travel Agent. We offer all kind of Holiday Packages in India, Tour Packages in India, Honeymoon Packages, India Package Tours, India Package Tour, Package Tours to India, Package Tour for India, Vacation Tours in India, India Vacation Tours. Full Article Entertainment
ind LGBT India Tours| Gay Lesbian Tour | Gay Travel Packages By investing.96.lt Published On :: Thu, 24 Aug 2017 09:06:53 UTC LGBT India Tours offers best and full assurance services to the gay, lesbian and LGBT clients at affordable rates for reveling holidays and tourism packages to various destinations in India. Full Article Entertainment
ind M. Sevala Naik | India and Jamaica: United in combating COVID-19 By jamaica-gleaner.com Published On :: Sun, 03 May 2020 00:11:35 -0500 The global COVID-19 spread has gone from bad to worse, with over 3.2 million confirmed cases and close to 250,000 deaths, not only has this pandemic claimed innumerable lives, it has also destabilised economies by freezing trade and other economic... Full Article
ind Antoinette Davis: The Beauty Behind Ettenio By jamaica-gleaner.com Published On :: Mon, 09 Mar 2020 00:14:05 -0500 Everyone these days is so focused on the beauty behind hair and skincare lines that they neglect to really explore the science behind them. Creating revolutionary products that are not only innovative but eco-friendly is entrepreneur Antoinette... Full Article
ind Is Love Truly Blind? By jamaica-gleaner.com Published On :: Mon, 09 Mar 2020 00:15:51 -0500 We’ve heard this rhetoric in RnB jams: love is blind. So it’s nothing new. But Netflix decided to test its theory with a show, designed to prove whether or not love can be truly blind, in its literal sense. It’s not until watching the episodes that... Full Article
ind Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger {beta}-Cell Failure By diabetes.diabetesjournals.org Published On :: 2020-01-20T12:00:26-08:00 Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes. Full Article
ind HB-EGF Signaling Is Required for Glucose-Induced Pancreatic {beta}-Cell Proliferation in Rats By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on epidermal growth factor receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β-cells in response to glucose in a carbohydrate-response element–binding protein (ChREBP)–dependent manner. In addition, chromatin immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand. Full Article
ind Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A+ NK6 homeobox 1+ cells and very few INS+ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells. Full Article
ind 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
ind Healthy Correa looks to put 2018 behind him By mlb.mlb.com Published On :: Sat, 16 Feb 2019 14:11:18 EDT You can't help but learn a few things when you had the kind of year Astros star shortstop Carlos Correa experienced last season, when a nagging back injury derailed him in the second half and forced him to deal with the biggest adversity of his career. Full Article
ind Chemical leak at LG plant in India kills 11, about 1,000 injured By jamaica-gleaner.com Published On :: Thu, 07 May 2020 10:14:15 -0500 HYDERABAD, India (AP) — A gas leak at a chemical factory owned by a South Korean company in southern India early Thursday left at least 11 people dead and about 1,000 struggling to breathe. The chemical styrene, used to make plastic and... Full Article
ind Windies players lack commitment – Benjamin By jamaica-gleaner.com Published On :: Sat, 09 May 2020 00:13:16 -0500 BRIDGETOWN, Barbados (CMC): Former Windies fast bowler Kenny Benjamin says that cricket in the Caribbean is suffering from players’ lack of loyalty and commitment and that intervention is required to save the sport. The Antiguan called for coaches... Full Article
ind Hexed - JFF finds possible World Cup Qualifying structure changes ‘disadvantageous’ By jamaica-gleaner.com Published On :: Sat, 09 May 2020 00:14:49 -0500 Jamaica Football Federation (JFF) general secretary Dalton Wint says that any potential changes to the Concacaf hexagonal round for the FIFA World Cup qualifiers could present challenges to the nation’s aim of qualifying for Qatar 2022. Wint’s... Full Article
ind Management of cancer induced bone pain By feeds.bmj.com Published On :: Fri, 30 Jan 2015 17:07:05 +0000 Bone pain is the most common type of pain from cancer and is present in around one third of patients with bone metastases, currently, improvements in cancer treatments mean that many patients are living with metastatic cancer for several years. Christopher Kane, NIHR academic clinical fellow in palliative medicine at Leeds University School of... Full Article
ind Unexpected findings, with uncertain implications, in research imaging By feeds.bmj.com Published On :: Fri, 13 Nov 2015 16:20:27 +0000 When healthy volunteers are scanned as part of a research project, unexpected findings, with uncertain implications, can be thrown up. Joanna Wardlaw, professor of applied neuroimaging and honorary consultant neuroradiologist at the University of Edinburgh, joins us to discuss how her group deals with these incidental findings, and what... Full Article
ind Exercise induced bronchoconstriction By feeds.bmj.com Published On :: Sat, 09 Jan 2016 16:17:18 +0000 James Smoliga, from High Point University, North Carolina, and Ken Rundell, from The Commonwealth Medical College, Pennsylvania, join us to discuss how to test for, and manage, exercise induced bronchoconstriction, and particularly how to distinguish it from other respiratory conditions. Read the full review at... Full Article
ind Blinding the randomisation By feeds.bmj.com Published On :: Fri, 18 Nov 2016 15:58:27 +0000 Allocation concealment - blinding which arm of a trial a patient is randomised to - is being questioned in an analysis published on thebmj.com. David Torgerson, director of the York Trials Unit at the university of York and colleagues have been looking at the way in which trials do this randomisation, and how they subsequently report it - and... Full Article
ind Finding out who funds patient groups By feeds.bmj.com Published On :: Wed, 29 May 2019 16:32:22 +0000 We’ve been banging the drum about transparency of payment to doctors for years - we’ve even put a moratorium on financial conflicts of interest in the authors of any of our education articles. Not because we think that all doctors who receive money from industry are being influenced to push their agenda - but because we have no way of telling when... Full Article
ind Behind the campaign promises - GP numbers, and appointment slots By feeds.bmj.com Published On :: Fri, 15 Nov 2019 16:59:59 +0000 A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week has... Full Article
ind Behind the campaign promises - Health and social care spending By feeds.bmj.com Published On :: Fri, 22 Nov 2019 16:21:30 +0000 A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week... Full Article
ind Behind the campaign promises - Health beyond the NHS By feeds.bmj.com Published On :: Sat, 30 Nov 2019 09:10:48 +0000 A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week... Full Article
ind Behind the campaign promises - what the NHS means for the election By feeds.bmj.com Published On :: Thu, 05 Dec 2019 19:09:30 +0000 UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week we're... Full Article
ind Behind the campaign promises - Doctors in parliament By feeds.bmj.com Published On :: Mon, 09 Dec 2019 18:52:26 +0000 The UK general election is happening this week, and you’ve probably made your mind up which MP you’re voting for already - and maybe the NHS has influenced that decision. This year has seen an increase in the number of doctors running for parliament, and in this podcast we find out what motivates doctors to step away from clinical practice, and... Full Article
