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...

We’re back! Hope you’re as excited as we are to do some learning! Let’s ease into things though, no one wants to learn about hems every week. So this week we’re gonna look at collection based words that describe how fashion is compiled! Dweek! Say...

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...

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The theme for international Women’s Day 2020 is #EachforEqual which focuses on building a gender-equal world, which will be healthier, wealthier and more harmonious. The World Economic Forum, a non-aligned European-based intellectual group,...

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...

Novelist, writer and designer Edith Wharton once said, “There are two ways of spreading light – to be the candle or the mirror that reflects it”. Shining a light of faith and hope for girls through the provision of an open and safe place is Britney...

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...

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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...

It is definitely a make-or-break season for those trying to balance career and COVID-19 at home. For some, it is the ideal time to reconnect with themselves, family members and get creative with work. While with others, the cookie crumbles and they...

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.

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.

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.

Henry "Hank" Aaron was born in Alabama three years after Willie Mays, 85 years ago Tuesday. Now, all this time later, Aaron is as much the conscience and the soul of baseball as any man alive. But we don't just celebrate a great baseball life today. We celebrate a great American life.

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.

Here are answers to some of the primary questions you may have as the defending National League East champs prepare to begin Spring Training next week.

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.

As the Mets, Nationals and Phillies have made multiple upgrades, Braves GM Alex Anthopoulos has thus far limited his offseason activity to giving Josh Donaldson a record one-year deal and bringing to fruition the desires of Brian McCann and Nick Markakis to play for the Braves.

Here's a look at 10 stars that you may have forgotten played for the Braves.

Reporter Mark Bowman addresses the Braves' offseason as a whole, as well as identifying a Minor League who has a chance at making the club out of Spring Training.

When the Braves open Spring Training next week, their bid to defend their National League East crown will be significantly influenced by whether Josh Donaldson is capable of reestablishing himself as one of baseball's elite superstars.

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.

At some point over the next six weeks, injuries, improvement or regression will inevitably alter the plan nearly every Major League club brings into Spring Training. The Braves must decide exactly how to round out their rotation and bullpen, but for now it looks like they won't have any position-player battles. Here's the first prediction of how Atlanta's Opening Day roster might look.

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.

The 30 prospects below all are getting very long looks this spring with an eye toward breaking camp with the parent club. Even if they start the year in the Minors, they all should get the chance to contribute at some point in the very near future.

We're reluctant to finalize our list of offseason winners because, as you may have heard, there are some prominent unsigned free agents. Not just Bryce Harper and Manny Machado, either.

It didn't come as a surprise to anyone when Dana Brown left the Blue Jays as a special assistant to general manager Ross Atkins to join the Braves as vice president of scouting.

Here is a look at 10 Braves players sure to draw attention during this year's Spring Training.

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.

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.