stor

CBD News: The Society for Ecological Restoration has conferred its 2011 Special Recognition Award to the Parties to the Convention on Biological Diversity (CBD) at the Gala Awards Banquet on 23 August 2011 in Mérida, Yucatán, Mexico, on the marg




stor

CBD Restoring the Earth: Botanic Gardens join forces to launch Ecological Restoration Alliance




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CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary on the occasion of the Capacity-Building Workshop for the Pacific on Ecosystem Conservation and Restoration and the Pacific Sub-Regional Capacity-Building Workshop on the N




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CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary, on the occasion of the Capacity-Building Workshop for West Asia and North Africa on Ecosystem Conservation and Restoration to Support Achievement of the Aichi Biodiversity




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CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary, on the occasion of the Capacity-Building Workshop for Southeast Asia on Ecosystem Conservation and Restoration to Support Achievement of the Aichi Biodiversity Targets, Ja




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CBD News: Statement by Mr. Braulio Ferreira De Souza Dias, Executive Secretary of the Convention on Biological Diversity on The Occasion Of Capacity-Building Workshop for Southern and Eastern Africa on Ecosystem Conservation and Restoration to Support Ach




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CBD News: The Korea Forest Service launched the Forest Ecosystem Restoration Initiative (FERI) in the margins of the twelfth meeting of the Conference of the Parties to the Convention on Biological Diversity (COP 12)




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CBD News: Statement by Mr. Braulio F. de Souza Dias, CBD Executive Secretary, on the occasion of the Bonn Challenge 2.0: Implementing Restoration Partnerships High Level Roundtable, Bonn-Bad Godesberg, Germany, 20 March 2015




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CBD News: On 21 March 2015 the CBD Secretariat and the Korea Forest Service signed a Memorandum of Understanding for implementation of the Forest Ecosystem Restoration Initiative.




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CBD News: Indigenous peoples and local communities often refer to this Earth as Pachamama or "Mother Earth." The fate of Pachamama and of humans has been shaped over a history that has been intertwined.




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CBD News: On 10 June, HSH Prince Albert II of Monaco closed a historic meeting of biodiversity and Antarctic experts. The purpose of the meeting was to examine the extent to which conservation of the biodiversity of Antarctica and the Southern Ocean is re




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CBD News: Poverty eradication is one of the greatest global challenges facing us today. Fortunately, the conservation, restoration and sustainable use of biodiversity can provide solutions to a range of societal challenges and is critical to achieving the




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CBD News: It is a pleasure to join you here in Kuala Lumpur for the fourth session of the IPBES Plenary. We come together for a very exciting moment in the history of IPBES, when the Plenary will be presented with the first two assessments for its accepta




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CBD News: This is a historic day in the life of our Convention on Biological Diversity for two reasons. First, we open the first meeting of this body, the Subsidiary Body on Implementation. Second, the Secretariat celebrates 20 years in this beautiful and




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CBD News: As a vital part of biodiversity, migratory birds play key functions in the interconnected systems that keep nature healthy, including seed dispersal of plants for human and livestock consumption, ecosystem restoration and pest regulation, in add




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CBD News: This year's World Day to Combat Desertification shows the importance of being inclusive as we cooperate to restore and rehabilitate degraded land. It also points to the convergence of international action and landmark agreements recently ado




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CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary, on the occasion of the Capacity-Building Workshop for Subregions of Asia on the Restoration of Forests and Other Ecosystems to Support the Achievement of the Aichi Biodive




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CBD News: While many countries have made significant advances, indigenous peoples continue to face challenges in accessing their right to education, in particular their right to access a culturally appropriate education inclusive of their histories, world




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CBD News: The Mexican Alliance for Biodiversity and Business, with the aim of promoting the protection, conservation and restoration of biodiversity and ecosystems, was launched 17 October 2016 in Mexico City.




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CBD News: We, legislators gathered together on the occasion of the CBD COP13 Legislators Forum at the United Nations Biodiversity Conference, Cancun, Mexico, 2016, on 7 December 2016, have discussed practical strategies and success stories in promoting th




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CBD News: The focus of work this week "towards an enhanced regional cooperation to restore Mediterranean landscapes: improving ecosystem resilience for the benefit of people and the environment.", directly supports the Strategic Plan for Biodive




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CBD News: As we all know, the business and environment communities were historically not close allies. It was long believed that economic growth could not be compatible with a healthy environment. Thankfully, that has changed. We now know that the conserv




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CBD News: Statement by Ms. Cristiana Pa?ca Palmer, Executive Secretary of the Convention on Biological Diversity, on the occasion of the African Ministerial Summit on Biodiversity: "Land and ecosystem degradation and restoration: Priorities for incre




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CBD News: The film highlights the importance of nature in tackling climate change, calling for the need to protect, restore and fund nature and mobilizing attention to scale nature-based solutions.




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CBD Notification SCBD/SSSF/AS/SBG/LJ/88547 (2020-005): Subregional Exchange for the Caribbean on the Restoration of Forests and Other Ecosystems, Castries, Saint Lucia - 9 to 13 March 2020




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CBD News: Subregional exchange for the Caribbean on the restoration of forests and other ecosystems




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CBD News: Statement by Ms. Elizabeth Maruma Mrema, Acting Executive Secretary of the Convention on Biological Diversity, at the opening of the Subregional Exchange for the Caribbean on the Restoration of Forests and Other Ecosystems, 9-13 March 2020




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History show heads to Kowloon City

The Leisure & Cultural Services Department’s Community Oral History Theatre Project will be launched in Kowloon City District on January 15.

 

An oral history theatre performance and a sharing session will kick off the project.

 

The performance will feature an excerpt from the production of Sai Kung, Therefore I Live.

 

It will be held at Hung Hom Community Hall.

 

Admission is free with tickets.

 

Click here for details.




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A Brief History of the Development of Diabetes Medications

John R. White
May 1, 2014; 27:82-86
From Research to Practice




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Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




stor

ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells [Molecular Bases of Disease]

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.




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SAS Notes for SAS®9 - 65925: Clicking a URL for a stored process in Excel brings up the SAS Stored Process Web Application Welcome page

After you submit a stored process from the SAS Stored Process Web Application, the generated URL is placed into a cell in a Microsoft Excel worksheet. When you click this URL, you expect that the stored process is sub




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SAS Notes for SAS®9 - 34114: Creating a detailed SAS Stored Process Server log by default

The SAS Stored Process Server does not create a detailed log file by default. However, you can create a detailed SAS Stored Process Server log file (that will contain information about all of the code that was executed) by using this approach. AUTO




stor

Cool Met Stuff, rainstorms, Hong Kong, summer, loss of property, casualties, reviews, extreme torrential rain

Every summer, rainstorms occur in Hong Kong occasionally, leading to loss of property or even casualties.




stor

The story of three African slaves during Spanish colonialism, as told by their bones

(Cell Press) In a study appearing April 30 in the journal Current Biology, scientists tell the story of three 16th century African slaves identified from a mass burial site in Mexico City. Using a combination of genetic, osteological, and isotope analyses, the scientists determined from where in Africa they were likely captured, the physical hardships they experienced as slaves, and what novel pathogens they may have carried with them across the Atlantic.




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African skeletons from early colonial Mexico tell the story of first-generation slaves

(Max Planck Institute for the Science of Human History) Three 16th-century skeletons from a mass burial in Mexico City highlight the role of the transatlantic slave trade in introducing and disseminating new pathogens to the Americas. Researchers from the Max Planck Institute for the Science of Human History and Escuela Nacional de Antropología e Historia in Mexico analyzed skeletal features, genetic data and isotopes to explore the life history of three enslaved Africans and explore the wide-ranging impacts of massive forced migration.




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Sleeter receives funding for historical simulations on diplomacy

(George Mason University) Nathan Sleeter, Research Assistant Professor, Roy Rosenzweig Center for History and New Media (RRCHNM), is directing a project in which RRCHNM will create three classroom simulations based on events from the history of diplomacy for secondary education instructors.




stor

Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




stor

Construction of mega new IT data storage centre under way in Fyshwick

Fyshwick is set to get another massive IT data storage facility from 2018.




stor

A Credit-fuelled Economic Recovery Stores Up Trouble for Turkey

17 February 2020

Fadi Hakura

Consulting Fellow, Europe Programme
Turkey is repeating the mistakes that led to the 2018 lira crisis and another freefall for the currency may not be far off.

2020-02-17-TurCB.jpg

Headquarters of the Central Bank of the Republic of Turkey. Photo: Getty Images.

Since the 2018 economic crisis, when the value of the lira plummeted and borrowing costs soared, Turkey’s economy has achieved a miraculous ‘V-shaped’ economic recovery from a recession lasting three quarters to a return back to quarterly growth above 1 per cent in the first three months of 2019.

But this quick turnaround has been built on vast amounts of cheap credit used to re-stimulate a consumption and construction boom. This so-called ‘triple C’ economy generated a rapid growth spurt akin to a modestly able professional sprinter injected with steroids.

This has made the currency vulnerable. The lira has steadily depreciated by 11 per cent against the US dollar since the beginning of 2019 and crossed the rate of 6 lira versus the US dollar on 7 February. And there are further warning signs on the horizon.

Credit bonanza

Statistics reveal that Turkish domestic credit grew by around 13 per cent on average throughout 2019.  The credit bonanza is still ongoing. Mortgage-backed home sales jumped by a record high of 600 per cent last December alone and the 2019 budget deficit catapulted by 70 per cent due to higher government spending.

Turkey’s central bank fuelled this credit expansion by cutting interest rates aggressively to below inflation and, since the start of this year, purchasing lira-denominated bonds equivalent to around one-third of total acquisitions last year to push yields lower.

Equally, it has linked bank lending to reserve requirements – the money that banks have to keep at the central bank – to boost borrowings via state and private banks. Banks with a ‘real’ loan growth (including inflation) of between 5 and 15 per cent enjoy a 2 per cent reserve ratio on most lira deposits, which authorities adjusted from an earlier band of 10-20 per cent that did not consider double-digit inflation.

Cumulatively, bond purchases (effectively quantitative easing) and reserve management policies have also contributed to eased credit conditions.

Commercial banks have also reduced deposit rates on lira accounts to less than inflation to encourage consumption over saving. Together with low lending rates, the boost to the economy has flowed via mortgages, credit card loans, vehicle leasing transactions and general business borrowings.

Accordingly, stimulus is at the forefront of the government’s economic approach, as it was in 2017 and 2018. It does not seem to be implementing structural change to re-orient growth away from consumption towards productivity. 

In addition, governance is, again, a central issue. President Recep Tayyip Erdogan’s near total monopolization of policymaking means he guides all domestic and external policies. He forced out the previous central bank governor, Murat Cetinkaya, in July 2019 because he did not share the president’s desire for an accelerated pace of interest rate reductions.

New challenges

Despite the similarities, the expected future financial turbulence will be materially different from its 2018 predecessor in four crucial respects. 

Firstly, foreign investors will only be marginally involved. Turkey has shut out foreign investors since 2018 from lira-denominated assets by restricting lira swap arrangements. Unsurprisingly, the non-resident holdings of lira bonds has plummeted from 20 per cent in 2018 to less than 10 per cent today.

Secondly, the Turkish government has recently introduced indirect domestic capital controls by constraining most commercial transactions to the lira rather than to the US dollar or euro to reduce foreign currency demand in light of short-term external debt obligations of $191 billion.

Thirdly, the Turkish state banks are intervening quite regularly to soften Lira volatility, thereby transitioning from a ‘free float’ to a ‘managed float’. So far, they have spent over $37 billion over the last two years in a futile effort to buttress the lira. This level of involvement in currency markets cannot be maintained.

Fourthly, the Turkish state is being far more interventionist in the Turkish stock exchange and bond markets to keep asset prices elevated. Government-controlled local funds have participated in the Borsa Istanbul and state banks in sovereign debt to sustain rallies or reverse a bear market.  

All these measures have one running idea: exclude foreign investors and no crisis will recur. Yet, when the credit boom heads to a downturn sooner or later, Turks will probably escalate lira conversions to US dollars; 51 per cent of all Turkish bank deposits are already dollar-denominated and the figure is still rising.

If Turkey’s limited foreign reserves cannot satisfy the domestic dollar demand, the government may have to impose comprehensive capital controls and allow for a double digit depreciation in the value of the lira to from its current level, with significant repercussions on Turkey’s political stability and economic climate.

To avoid this scenario, it needs to restore fiscal and monetary prudence, deal the with the foreign debt overhang in the private sector and focus on productivity-improving economic and institutional reforms to gain the confidence of global financial markets and Turks alike.




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Episode 26 - The Internet of Small Hands Big Phones (IoSHBP) Galaxy Note7, GDS & Instagram stories

Matt Egan is back in the hosting chair to chat with producer Chris about the Samsung Galaxy Note 7 and how we feel about phablets. Techworld.com editor Charlotte Jee comes in to explain what is going on at the GDS (government digital service) and why we should care (13:00). Then online editor at Techworld.com Scott Carey chats Instagram stories, why it is a blatant rip off of Snapchat stories and how the social media giant can get away with being so brazen (22:00).  


See acast.com/privacy for privacy and opt-out information.




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Algeria’s Perfect Storm: COVID-19 and Its Fallout

6 May 2020

Adel Hamaizia

Associate Fellow, Middle East and North Africa Programme

Yahia H. Zoubir

Senior Professor of International Studies, KEDGE Business School; Visiting Fellow, Brookings Doha Center
Coronavirus is a godsend for Algeria’s government to introduce restrictive measures beyond those needed to contain COVID-19. But its new leaders are missing a chance to gain legitimacy, which will offset the socio-economic fallout of the drop in oil prices.

2020-05-06-Algeria-Health-Covid

Algerian volunteers prepare personal protection equipment (PPE) to help combat the coronavirus epidemic in the capital Algiers. Photo by RYAD KRAMDI/AFP via Getty Images.

Although protests successfully ended Abdelaziz Bouteflika’s 20-year sultanistic rule a little over one year ago, demands have been continuing to dismantle the system, get rid of the old personnel, and institute democracy.

The controversial election in December of Abdelmadjid Tebboune — who has inherited a disastrous situation — has not tempered the determination of the Hirak protest movement. As a former minister and prime minister under Bouteflika, the new president has won little legitimacy, and protests have continued.

Now COVID-19 is worsening already dire economic conditions, such as a sharp drop in oil prices. By the beginning of May, statistics showed 10% of confirmed cases have ended in fatality, the highest percentage in the region.

Maintaining an authoritarian style

Hirak had already called for the suspension of the marches — mobilising online instead — before the government’s measures, which include curfews and lockdowns, demonstrating a high sense of duty. But instead of appeasing Hirak’s demands, the government has maintained the authoritarian style of its predecessors.

Tebboune released more than 5,000 prisoners on March 31 but kept prisoners of conscience and leaders of the hirak imprisoned, then subsequently imprisoned journalists and activists. It even passed a controversial penal law, that also covers fake news, and may be used to justify actions against journalists.

The regime wishes to see an end to the Hirak, and rejects accusations of totalitarianism by insisting freedom and a democratic climate exist in Algeria.

Tebboune’s actions contradict his praise for the ‘blessed’ hirak and his promises of instituting the rule of law. In proclaiming the measures, the government has shown disappointing leadership, acting in an authoritarian fashion.

Tebboune also declared proudly that Algeria was fully prepared to fight the coronavirus epidemic, an optimistic claim given the country has only 400 intensive care unit (ICU) beds, or one per 100,000 people. Despite hundreds of billions of hydrocarbon dollars accumulating during the Bouteflika-era, Algeria’s health system ranks 173 out of 195 countries.

Algerians often refer to hospitals as ‘mouroirs’, meaning ‘places for the dying’. Not only has the state failed to build modern hospitals but basic hygienic conditions are lacking, and government officials prefer being treated overseas. A 2014 project to build five university hospitals was abandoned, leaving the health sector in deplorable shape.

Before Chinese assistance arrived, the glaring lack of equipment to protect caregivers and care for the sick was evident. Prime Minister Abdelaziz Djerad admitted the health system required a ‘total overhaul’. The president recently stated Algeria’s doctors are among the 'best in the world' but didn't address why almost 15,000 Algerian doctors practice in France.

Strict containment measures are in sync with most countries but implementation is challenging when most people live in overcrowded urban dwellings (the average household consists of 5.9 members).

Water shortages in many areas makes good hygiene and decontamination impossible, while schools and universities find online teaching difficult when many students do not possess laptops or internet connections. And only 20% of Algerians have debit cards in a cash-dominated economy because of low trust in the public-dominated banking sector, making online shopping capability low.

An already declining macroeconomic situation is worsening due to COVID-19. The IMF revised its 2020 estimates for Algeria, forecasting a catastrophic contraction of -5.2% in a country where hydrocarbons account for 93% of export revenues and 60% of its budget.

Foreign currency reserves are now an estimated $55 billion (expected to fall to $44billion by the end of 2020), down from $200 billion in 2014, and Algerian crude has recently traded close to production costs, with the fiscal breakeven oil price at $157.

In line with its historic aversion to external borrowing, Tebboune recently ruled out seeking financial support from the ‘IMF or other foreign banks’, as he argued such borrowing undermines sovereign foreign policy because - when indebted - ‘we cannot talk about either Palestine or Western Sahara’, two causes dear to Algeria. ‘Friendly countries’ - most likely a reference to China - are said to have offered to grant loans which have been declined for now.

The government is forecasted to face a 20% budget shortfall this year, but Algeria’s fiscal response to COVID-19 is actually the largest among the regional hydrocarbon exporters at an estimated 8% of GDP, compared to an average of 3.2%. However, the government revised downwards its 2020 public spending by 50% (a second cut in a month, from an initial 30% reduction), halting state projects and slashing its $41 billion import bill by 25% while expanding agricultural production. National oil company SONATRACH will also cut planned investment by half to $7 billion but plans have been revealed to develop other natural resources including gold, uranium and phosphates.

But recent growth rates are insufficient to create jobs for those entering the labour market. Despite government attempts to support a rather anaemic ‘formal’ private sector, estimates are 700,000 jobs could be lost due to potential bankruptcies from reduced activity and a loss of markets abroad.

Facing potential social unrest and the quasi-preservation of a tired social contract, the government has committed to upholding public sector wages - including for 50% of the civil servants told to stay home - protecting sacrosanct, unsustainable subsidies, and increasing health expenditure to strengthen the capacity to combat COVID-19.

A supplementary finance law will include various measures that support businesses and the economic fallout. However, while the government is to be commended for its efforts to aid businesses, supporting large swathes of the population is challenging as approximately 50% of the workforce operate in the informal economy.

Weak administrative capacity and insufficient data to implement cash transfers makes the planned ‘solidarity allowance’ of 10,000 dinars ($80) for Ramadan difficult to allocate to those who most need it (especially those in the informal sector). Families, communities, and religious organisations continue to be a social safety net.

So COVID-19 has not created new problems, it has merely magnified and exacerbated the numerous inequalities and failures of the Bouteflika regime to sufficiently invest in human security (economic, food, health environmental, personal, community, and political). Typically, whenever oil prices and related earnings dwindle, the political system promises to reform and diversify the economy. Tebboune is repeating this same old tune.

There are positive elements, such as the government’s realization it must initiate genuine reforms. And local enterprises have been successfully producing artificial respirators, surgical masks, and other materials. Algerians, including the Hirak, are showing great social solidarity.

But the government must capitalize on these positive actions by introducing real change. Because, if not, Hirak will certainly be back in force once the crisis is over, and operating in an environment of worsening socioeconomic problems. The medicine of the past will not work.




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Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage [Research Articles]

Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. The function of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP in regulating the secretion of FL-CETP by cells and explored its possible role in intracellular lipid metabolism. CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, and showed that cellular FL- and E9-deleted CETP form an isolatable complex. Coexpression of CETP isoforms lowered cellular levels of both proteins and impaired FL-CETP secretion. These effects were due to reduced synthesis of both isoforms; however, the predominate consequence of FL- and E9-deleted CETP coexpression is impaired FL-CETP synthesis. We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. We conclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels and impair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellular TG metabolism and storage but in a contrary manner.




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Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles]

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.




stor

ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells [Molecular Bases of Disease]

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.




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Novel Detection and Restorative Levodopa Treatment for Pre-Clinical Diabetic Retinopathy

Diabetic retinopathy (DR) is diagnosed clinically by directly viewing retinal vascular changes during ophthalmoscopy or through fundus photographs. However, electroretinography (ERG) studies in humans and rodents have revealed that retinal dysfunction is demonstrable prior to the development of visible vascular defects. Specifically, delays in dark-adapted ERG oscillatory potential (OP) implicit times in response to dim flash stimuli (<-1.8 log cd·s/m2) occur prior to clinically-recognized diabetic retinopathy. Animal studies suggest that retinal dopamine deficiency underlies these early functional deficits. Here, we randomized persons with diabetes, without clinically detectable retinopathy, to treatment with either low or high dose Sinemet (levodopa plus carbidopa) for 2 weeks and compared their ERG findings with those of control (no DM) subjects. We assessed dim flash stimulated OP delays using a novel hand-held ERG system (RETeval) at baseline, 2 and 4 weeks. RETeval recordings identified significant OP implicit-time delays in persons with diabetes without retinopathy compared to age-matched controls (p<0.001). After two weeks of Sinemet treatment, OP implicit times were restored to control values, and these improvements persisted even after a two-week washout. We conclude that detection of dim flash OP delays could provide early detection of DR, and that Sinemet treatment may reverse retinal dysfunction.




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Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils [Computational Biology]

Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis.




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Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis

Jay S. Skyler
Feb 1, 2017; 66:241-255
Perspectives in Diabetes




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Screening Room: Parts of a Circle - History of the Karabakh Conflict

Members Event

18 February 2020 - 6:00pm to 8:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Jenny Norton, Producer, Parts of a Circle: History of the Karabakh Conflict
Famil Ismayilov, Journalist
Leon Aslanov, Middle East Analyst, Integrity UK
Chair: Laurence Broers, Associate Fellow, Russia and Eurasia Programme, Chatham House; Director, Caucasus Programme, Conciliation Resources

Once an autonomous region populated mainly by Armenians in Soviet Azerbaijan, Nagorny Karabakh, is a contested territory in the Caucasus. Since the late 1980s, its contested status has driven popular mobilization among Armenians and Azerbaijanis and an all-out war between 1992-94. After a quarter-century of enmity and military build-up, in 2019, Armenian and Azerbaijani leaders agreed to ‘prepare their populations for peace’ but how would this work in practice?

Parts of a Circle: History of the Karabakh Conflict (2019) chronicles the disputed history of the decades-old conflict between Armenians and Azerbaijanis. Supported by the European Union and based on a series of three documentary films jointly produced over four years by Armenian and Azerbaijani production teams, the film showcases journalistic cooperation in bridging societies in conflict.

The screening was followed by a panel discussion that will explore the state of the conflict and the efforts to end it. Why have efforts to resolve the conflict between Azerbaijan and Armenia not been successful? How can both sides build grassroot support for peace after years of fomenting hatred? And what can the international community do in support?

A short film about the making of the documentary can be seen here.

Members Events Team




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Carbon Capture and Storage: Panacea or Procrastination?

Research Event

14 September 2009 - 12:00am to 11:00pm

Chatham House, London

Event participants

Dr Jon Gibbins, Senior Lecturer in the Department of Mechanical Engineering, Imperial College London
Jim Footner, Senior Climate Change Campaigner, Greenpeace

Carbon capture and storage (CCS) has risen up the political agenda both nationally and internationally as a part of the effort to reduce CO2 emissions in power generation yet the applications, potential and impacts of this technology remain contested.

Is CCS - employed to produce low-carbon electricity and hydrogen - the panacea we urgently need to limit cumulative CO2 emissions to a level at which we stand a chance of avoiding dangerous climate change (and possibly also a renaissance in global nuclear fission)? Or does it shift the emphasis away from switching to more a sustainable renewable energy infrastructure that could avoid the use of fossil fuels and nuclear altogether?

In this meeting two leading voices in the debate give their opinions, separating the known from the unknown and kick starting an informed discussion about the pros, cons and politics of CCS.

Please note that attendance is by invitation only and there is a maximum of 25 places. 

This meeting is part of the Chatham House Fossil Fuels Expert Roundtable.

Event attributes

All-day event