Government, having said bye, bye to the International Monetary Fund (IMF), declared quite boldly that it was ready to take charge and defend, on its own, the country’s economic independence. For the Government to swallow its pride and say, “Please...

A few days ago as the lady and I drove out, headed to the hardware store to purchase one piece of lumber, she was wearing a face mask, and I had mine on the seat behind me. “So, what’s the point of you wearing the mask in the car and me without...

In this article, I share my two final case studies, which examine changing our cultural attitudes to enhance productivity. Case study #5 – The role of punctuality An entrepreneur named Michael Fairbanks, who specialises in developing...

Public reaction to the initial threat of the coronavirus (COVID-19) was predictably mixed. While international news of the contagion across continents helped people to appreciate that this was not restricted to a particular region, not many people...

Many of us may feel right at this minute that in the same way the 19th-century American poet Edgar Allan Poe painted it in his tortured poem, The Conqueror Worm, we are sitting in a theatre, watching a play of hopes and fears “While the orchestra...

On Tuesday, April 14, the International Monetary Fund downgraded Jamaica’s growth prospects to -5.6 per cent. This is a severe contraction warranting substantial Government intervention. However, at times, the Government waits too late to respond...

Four companies involved in one of America’s “largest price-fixing cases” are now behind the anti-malaria drug touted by Donald ‘The Great Impeached’ Trump as a snake-oil, cure-all treatment for COVID-19, caused by the novel coronavirus. Several...

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...

The lessons of COVID-19 are yet to crystallise, but the evidence so far has yielded some early insights of developments that are likely to shape the national and global agenda for the immediate future. The speed and scale of the spread of the...

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...

I cannot quite remember the exact day he called me, but I know that it was sometime in the early 1990s. Six weeks before that, he was selected as constituency caretaker for a rough garrison seat that was going through some changes, slowly but...

Michelle Thomas has joined the ranks of society’s young movers and shakers in her capacity as a lawyer. The work truly began after she was crowned Miss Kingston and St Andrew Festival Queen in 2015. Since then, she has been pushing for more female...

From formalising her father’s business and taking it to higher and more profitable heights to sitting on the board of EXIM Bank and lecturing in the field of business development, Lacey-Ann Bartley has earned her stripes as the Distinguished Woman...

Empathetic, God-fearing, humanitarian, motivated, and optimistic – these are just a few words that come to mind when one thinks of Dr Kazi-Ann Kasimbie. Dr Kasimbie is the CEO and founder of Psychfactor Consulting Services, a psychological...

Monique Lynch is a 29-year-old who believes her purpose is to improve the lives of those around her, especially the downtrodden and persons living with mental health issues. This angel-on-earth in the eyes of many is a Jill of several trades as...

Let’s face it, ladies: boosting your health is not always your primary priority, but it needs to be. It doesn’t require a long, overbearing and spine-chilling regime. Simple lifestyle changes can get the job done! In the end you’ll be left with a...

A hysterectomy is a surgical procedure that’s done to cure serious problems of the uterus (womb), cervix or even the ovaries. Some women fear that having this procedure done will affect their sex life. Will it truly? Let’s find out. “There are...

With passion, motivation and determination to go against what is deemed as conventional in today’s society, Flow hosted a staff summit ahead of the International Womens’ Day under the theme ‘Passion for Action’, which supports a collective will to...

M arketing guru and smashing entrepreneur Danielia McLean is known to the business and communication worlds as a powerhouse fiercely working to clutch success. Finding a novel business idea can be difficult; pursuing it, successfully, even more so...

At age 13, Nadeen Matthews Blair, chief executive officer of the NCB Foundation, challenged the tide to prove to a guidance counsellor at her United States-based school, that black girls can overcome all odds to become powerful leaders. Matthews...

Famous American poet and singer Maya Angelou shared this about matters pertaining to the heart: “Love recognises no barriers. It jumps hurdles, leaps fences, penetrates walls to arrive at its destination full of hope.” What started out as an...

“As the large wooden doors of the chapel opened and I saw my bride for the first time, our minds and hearts communicated in a way only love could evoke.” This sincere sentiment, echoed by the proud groom, only expresses a drop in the ocean of...

Women with endometriosis have significantly higher rates of depression than women in the general population. That’s according to psychiatrist Dr Kristen Robinson-Barrett. It’s the end of endometriosis month, so Flair spoke to the expert to explore...

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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.

Loss of functional β-cell mass is an essential feature of type 2 diabetes, and maintaining mature β-cell identity is important for preserving a functional β-cell mass. However, it is unclear how β-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature β-cell identity. Prmt1 knockout in fetal and adult β-cells induced diabetes, which was aggravated by high-fat diet–induced metabolic stress. Deletion of Prmt1 in adult β-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of β-cell identity. The expression levels of genes involved in mature β-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult β-cells. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CCCTC-binding factor (CTCF) and β-cell transcription factors. In addition, PRMT1-dependent open chromatin regions may show an association with the risk of diabetes in humans. Together, our results indicate that PRMT1 plays an essential role in maintaining β-cell identity by regulating chromatin accessibility.

Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and mouse pancreas over a range of ages and states of diabetes. Very few LDs were found in normal human juvenile pancreatic acinar and islet cells, with numbers subsequently increasing throughout adulthood. While accumulation appeared evenly distributed in postjuvenile acinar and islet cells in donors without diabetes, LDs were enriched in islet α- and β-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell–derived β-cell clusters. In contrast, LD accumulation was nearly undetectable in the adult rodent pancreas, even in hyperglycemic and hyperlipidemic models or 1.5-year-old mice. Taken together, there appear to be significant differences in pancreas islet cell lipid handling between species, and the human juvenile and adult cell populations. Moreover, our results suggest that LD enrichment could be impactful to T2D islet cell function.

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.

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.

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.

The Braves made it clear that, individually, each of their prospects was available in exchange for J.T. Realmuto. But they were not willing to provide the volume of prospects or the MLB-experienced asset sought by the Marlins, who ended an offseason-long saga by dealing the All-Star catcher to the Phillies on Thursday.

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

Here are the top players in each league who could get the opportunity to show what they can do at the highest level this year, perhaps even contending for Rookie of the Year honors

Those hoping to watch Ronald Acuna Jr. extend last season's incredible post-All-Star break production should remember that his pace would have equated to 45 homers and 33 stolen bases over 162 games.

Brian McCann still laughs about what transpired as he learned the Braves were calling him up to the Majors during the 2005 season. He remembers being summoned to Brian Snitker's room, where he found the then Double-A manager eating pizza while wearing nothing more than his underwear.

As the Braves open camp, they'll provide a glimpse of how much they have progressed since claiming an unexpected division crown last year. Freddie Freeman, Ronald Acuna Jr. and Ozzie Albies will once again be in a lineup that has been enriched by the addition of Josh Donaldson, the former American League MVP Award winner who thus far arguably ranks as baseball's top free-agent signee.

Freddie Freeman spent the offseason sharing excitement about the possibility that Josh Donaldson would not end up being the Braves' only significant offseason addition.

On this opening week of Spring Training, all 30 Major League teams have one thing in common: optimism. Here's an optimism cheat sheet for each of them.

As Braves manager Brian Snitker evaluates who might serve as his closer, A.J. Minter has made it clear he wants to be the guy who is consistently called upon to handle high-leverage threats that develop in late innings.

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.

Braves manager Brian Snitker joked that he could almost detect a smile as he shared a phone conversation with Nick Markakis after the stoic outfielder re-signed with the club in January. Snitker and others actually saw that smile on Tuesday morning, when Markakis reported to Spring Training to begin his fifth season with the Braves and attempt to push the club past the rebuild he positively enriched through his leadership.

Sean Newcomb entered last June as an All-Star candidate and exited the regular season wondering if he had done enough to earn a spot on Atlanta's postseason roster. The inconsistent nature of his first full Major League season enhances the difficulty of projecting how valuable he might be to the Braves from both an immediate and long-term perspective.

To those of a certain age, Frank Robinson was the definition of greatness, leadership and toughness. Well into his 70's and 80's, he carried himself with the confidence and unmistakable gait of a great athlete.

In outlining their plans to rebuild the Orioles following the least successful season in franchise history, new club officials routinely point to experience: They just did the same thing elsewhere.

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

The Orioles' crowded outfield mix gained another member on Monday when the team signed veteran Eric Young Jr. to a Minor League contract with an invitation to Spring Training.

For Brandon Hyde, the days and weeks leading up to Tuesday were filled with phone calls to friends, to former colleagues, to mentors he's made across more than two decades in the game. A constant theme emerged from the ensuing chats: What, exactly, should Hyde expect from his first Spring Training as a big league manager?

A year ago, Danny Farquhar was not going to be in the middle of a spring storyline. That's going to change this spring as he tries to win a spot in the Yankees' bullpen