Invitation Only Research Event

Event participants

Maia Sandu, President, Action and Solidarity Party; Prime Minister of Moldova (June-November 2019)
Chair: Cristina Gherasimov, Research Fellow, German Council on Foreign Relations; Academy Associate, Russia and Eurasia Programme, Chatham House
 

They’ve dimmed the lights getting ready to land service staff buckled down can’t see me pull out my camera, start clicking, clicking down the sci-fi lights, like some Twilight Zone episode where I’m holding my breath, waiting. Waiting for that thing You know, the thing the monster that tormented William Shatner, sitting in his youthful […]

I wish we had played on all night, African cowboys with not much, Else to do, I wish we had challenged the fish in the sea and, Called out to the Bison, My father and his band, And his -strike while the iron is hot- Jive, Johnstone, his brother, On the drums, Kicking up a […]

I don’t have friends, I do not think. Friends get married, and Drive bigger cars and, Have more intelligent things to talk about, better Places to go, are Becoming lawyers and doctors and ministers, Big people, and It sort of interrupts things. ♦photos♦ Jacob’s Ladder -short evocative poetry-

  My Gardener is enthusiastic. He kills all the weeds in my garden, Sweating conviction, In purple droplets, Muscles wet, In the midday sun, he Slaughters them, My perfect weeds I spent so long cultivating, Black, And whites ones, Jewish and Muslim, Mayhem. Now the name of Hebron formerly was Kiriath-arba. (Arba  was the greatest […]

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1 December 2009

24 May 2011

Research Event

Event participants

Lord Tu'ivakano, Prime Minister of the Kingdom of Tonga

22 October 2015

THE NOMENCLATURE ‘roots reggae artiste’ takes on a whole new classification when referencing singer Winston McAnuff. An elder statesman who has a fixation with an instrument which retains its genesis in the Church – the accordion – McAnuff, also...

It’s not news that the current fight against COVID-19 has overshadowed plans of artistes worldwide, having impacted some of their biggest stages and platforms with the cancellation of not only large-scale events but private ones as well. Birthday...

COVID-19 has completely readjusted how we operate daily. With the proliferation of the ‘work from home’ concept, many persons have become even more stationary as they spend full days on their couches, tapping on their communication devices while...

Reality hit home last week when Jamaican bars and their best friends in psychology class, churches, were ordered to radically scale down their activities. Bars, one of the mainstays of our women most socially and economically deprived, were ordered...

When I tell people that I do not remember learning how to read, they laugh. But I really do not recall learning to read. Reading was an activity that excited my family, and so it was no surprise that I would love reading. The love of books and...

As Jamaica signs off on Budget 2020-2021, we are still uncertain whether we will be able to withstand the economic onslaught that will accompany the crisis in the years to come. It is clear that this pandemic is like none other that we have seen...

A few weeks ago while I was hosting a Friday slot of Cliff Hughes Online, a caller engaged me in a brief discussion about a matter that was never at the forefront on my mind. According to him, the inclusion of another major player in the national...

A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell–specific Tph1 knockout (Tph1 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.

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.

Aging-dependent changes in tissue function are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity, and diabetes remain unclear. Lamin A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabolism and life span. Lamin C, albeit promoting obesity, increases life span, suggesting that this isoform is crucial for maintaining healthy conditions under metabolic stresses. Because β-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to β-cell function in physiopathological conditions. We demonstrate that aged lamin C only–expressing mice (Lmna^LCS/LCS) become obese but remain glucose tolerant due to adaptive mechanisms including increased β-cell mass and insulin secretion. Triggering diabetes in young mice revealed that Lmna^LCS/LCS animals normalize their fasting glycemia by both increasing insulin secretion and regenerating β-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in Lmna^LCS/LCS islets, two major processes involved in insulin secretion. Altogether, our results demonstrate for the first time that the sole expression of lamin C protects from glucose intolerance through a β-cell–adaptive transcriptional program during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for diabetes treatment.

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.

When the Braves re-signed Nick Markakis in January, they began leaning toward putting Ender Inciarte in the leadoff spot and moving Ronald Acuna Jr. to the cleanup role. But manager Brian Snitker said Acuna may still get his wish to stay at the top of the lineup.

While playing close to his Alabama home and enjoying a chance to once again work with Atlanta general manager Alex Anthopoulos, the former American League MVP Award winner Josh Donaldson also understands the importance of rejuvenating his career with his deal.

The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals’ susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual’s capacity to oxidize dietary fat is a metabolic determinant of weight change.

The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca²⁺ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects of capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all of the beneficial effects of capsaicin on alleviating reactive oxygen species generation, elevating mitochondrial activity, and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on the MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of the AMPK/SIRT3 pathway in the maintenance of BAT morphology and function and suggests that intervention in this pathway may be an effective target for preventing obesity- or age-related metabolic diseases.

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 (Hmgcr^m–/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 Hmgcr^m–/m– mice than in control Hmgcr^fl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcr^m–/m– and Hmgcr^fl/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.

The signing of veteran outfielder Michael Brantley by the Astros came a week after the Winter Meetings and only a few days before Christmas, meaning it didn't exactly garner much attention on national, or even local, news cycles. For the Astros, Brantley was exactly the player they needed at exactly the right price -- two years and $32 million -- and the kind of addition that should fire up the fanbase.

Spring Training is underway. Players around the league are stepping back onto the baseball field as they get ready for the 2019 season. MLB.com's beat reporters have you covered with the action from every team's training camp. Keep track of the latest highlights of Spring Training right here.

UNITED NATIONS (AP) — The United Nation’s leader said Wednesday the world’s one billion people living with disabilities are among the hardest hit by the coronavirus and called for them to have equal access to prevention and...

HARRISBURG, Pennsylvania (AP) — A Pennsylvania inmate whose dreadlocks violated a jail’s haircut policy has been released from solitary confinement after more than a year, although his federal lawsuit is still pending. A federal...

Pan American Health Organization (PAHO) director, Dr Carissa Etienne, is warning that lifting COVID-19 restrictions too soon could accelerate the spread of the virus and open the door for a dramatic upsurge in countries of the region. The warning...

HONOLULU (AP) — Hawaii authorities are cracking down on rogue tourists who are visiting beaches, riding personal watercraft, shopping and generally flouting strict requirements that they quarantine for 14 days after arriving. A newlywed...

WASHINGTON (AP) — President Donald Trump, who’s taken to calling the US the “king” of ventilators, is making plans to ship 8,000 of the breathing machines to foreign countries by the end of July to help in their fight...

OTTAWA, Canada (CMC): The Confederation of North, Central American and Caribbean Association Football’s (Concacaf) hexagonal round of qualifying for the 2022 FIFA World Cup in Qatar may have to be scrapped because of the disruption the COVID-19...

MADRID, Spain (AP): Rafael Nadal says Novak Djokovic will need to be vaccinated to keep playing if the governing bodies of tennis make coronavirus shots obligatory once they become available. Nadal told the Spanish newspaper La Voz de Galicia this...

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...

“Juliet”, a woman living in London, was diagnosed with a mysterious illness in November 2015, Ian Cropley, a consultant in infectious disease from The Royal Free London NHS Foundation Trust, was there to investigate. In this podcast, we find out how Zika, once a little known virus causing a rash and fever, has subsequently become a global health...

Medical error is not included on death certificates or in rankings of cause of death. Martin Makary, professor of surgery at Johns Hopkins University School of Medicine, joins us to explain why we don't measure medical error, and why it is so important that we start. Read the full analysis: http://www.bmj.com/content/353/bmj.i2139

Global evidence indicates that mandated treatment of drug dependence conflicts with drug users’ human rights and is not effective in treating addiction. Karsten Lunze, associate professor at the Boston University School of Medicine, joins us to describe the evidence, and why he is convinced seemingly counter intuitive hard reduction...

The European Medicines Agency (EMA) has embraced a new model of drug testing and marketing called “adaptive pathways”, allowing new drugs for “unmet medical needs” to be launched on the market faster, on the basis of fewer data. While industry claims this is necessary, an analysis on thebmj.com looks at the assumptions underlying the new pathway,...

In the UK, junk food advertising is banned on children’s TV - but manufactures are still able to target children in other ways.  A recent report from the WHO  "Tackling food marketing to children in a digital world", takes a look at the issue. In this podcast we're joined by João Breda, programme manager for nutrition physical activity and...

The UK government published its report Childhood Obesity: a Plan for Action, in August 2016. A new analysis article takes them to task for the inadequacy of that response to a growing problem. Neena Modi is a professor of neonatal medicine, at Imperial College London, and president of the Royal College of Paediatrics and Child Health, and joins...

Our latest debate asks whether there should be a Royal Commission (a high level enquiry, with statutory powers) into the future of the NHS. A high level inquiry could detoxify the radical changes needed and command wide support, say Maurice Saatchi, conservative peer, and Paul Buchanan, The BMJ's patient editor; but Nigel Crisp, independent peer,...

It’s been called “the universal panacea” - exercise has a positive effect on almost all health measures, and governments are actively campaigning for us to do more. But at the opposite end of the scale, the realisation that some people may be addicted to exercise is gaining traction. In this podcast we're joined by Heather Hausenblas - professor...

If you're a patient in the UK, increasingly, your first interaction with the healthcare system won't be the traditional face to fact chat with your doctor - instead you'll have a telephone consultation. The prevalence of these telephone consultations is increasing, and being promoted by CCGs and private companies who administer them - usually as...