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Mark Wignall | Party politics not for softies

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...




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Michelle Thomas – lawfully changing the game

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...




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Monique Lynch-Volunteering with a purpose

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...




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Maintaining health with simple lifestyle changes

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...




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Flow pushes passion for action for team members

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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Danielia Mclean A powerhouse in business

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...




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Ja’s women have combated and won in business

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...




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#PostingwithPurpose

“Don’t use social media to impress people, use it to impact people.” – Dave Willis This is the strategy used by The Distinguished’s 2020 Social Media Personality of the Year, Dr Terri-Karelle Reid, who has, in some aspect, impacted the...




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Island Wedding: A racing romance all the way to ‘I do’

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...




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Vox Pop: Coping with college and career in quarantine

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...




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Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger {beta}-Cell Failure

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.




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Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

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.




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Get ready to watch: MLB.TV available for 2019

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.




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Braves unwilling to meet Marlins' ask for J.T.

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.




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10 players you forgot were Braves

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




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Inbox: How to judge Braves' offseason?

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.




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30 low-key acquisitions who could pay off big

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.




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Prospects who should vie for a roster spot

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.




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Braves can still win the offseason

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.




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Brown is proud of Braves' rich history

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.




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10 Braves to watch in Spring Training

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




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Braves open camp with eyes on the prize

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.




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Freeman pleased with Braves' offseason deals

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




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Minter wants to be Braves' high-leverage option

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.




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The Braves' Spring Training battle to watch

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.




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Markakis enjoys reaping rewards of dedication

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.




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Newcomb's value depends highly on '19 growth

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.




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30 low-key acquisitions who could pay off big

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.




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Spring Training launches new era for Orioles

As pitchers and catchers reported Tuesday to Ed Smith Stadium, it marked the end to an offseason of overhaul in Baltimore, and the dawn of a new era. The focus will shift even further, from the front office to the field, when the club's first full squad workouts commence on Monday.




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Around the horn: Will Sisco be the starting C?

As we inch closer and closer to Opening Day, we'll continue to take a position-by-position look at the Orioles roster options and remaining questions. Now that pitchers and catchers have officially reported to Spring Training, now feels like a good time to take a look behind the plate, where the Orioles have a ton of options but no clear answer.




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Prospects who should vie for a roster spot

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.




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Now healthy, Karns looks to revive career

Everyone hopes for health this early in spring. But few more than Nate Karns, who has trudged a longer road back than any player in Orioles camp.




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Wave him bye bye: O's voice Angel retires

Wave him bye bye. A legendary voice of Orioles baseball is calling it a career. Joe Angel, beloved play-by-plan man and voice of the Orioles' radio broadcasts for nearly two decades, announced his retirement this week. The decision caps a 41-year career in the booth for Angel, 71, a fixture for 19 seasons across two stints in Baltimore.




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Davis embracing data, new approach to improve

Looking to preempt questions about his work ethic in a nightmare 2018 season, Chris Davis reported to Spring Training in Florida more than a week before Orioles position players were required to. That's when his efforts to rebound hit their first minor snag.




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Top prospect Diaz looks to break camp with O's

A lot has to go right for Yusniel Diaz to crack the Orioles' Opening Day roster. But the Orioles' No.1 prospect per MLB Pipeline isn't letting that impede his plans to compete for a spot anyway.




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Wilkerson is Orioles' man of many gloves

Steve Wilkerson enters Orioles camp competing for a super-utility role after a brief big league cameo last year. He isn't traveling light, as Wilkerson has 10 gloves on display.




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O's pitchers welcoming high-tech revolution

Like so many pitchers in Major League camps, Orioles hurlers have extra sets of eyes on them this spring. The Edgertronic cameras, perched on tripods, are set about a stride's length beyond the backfield bullpen mounds at the club's Ed Smith Stadium complex, as conspicuous as the coaches standing cross-armed behind them.




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The Orioles' Spring Training battle to watch

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.




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Here are 12 Orioles to watch in spring camp

In holding their first full-squad workout on Monday, the Orioles ushered in the first official phase of a spring set to surprise. Fresh faces flood Ed Smith Stadium. Questions litter the roster. Battles abound at nearly every position.




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Pitch clocks nothing new to younger players

Pitch clocks are set to make their Spring Training debuts this week, and it will be in games featuring hordes of players for whom playing on a timer is nothing new.




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Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults

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.




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Inhibition of Mitochondrial Calcium Overload by SIRT3 Prevents Obesity- or Age-Related Whitening of Brown Adipose Tissue

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.




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30 low-key acquisitions who could pay off big

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.




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Especially for Altuve, Marwin's presence missed

The reality is setting in for Astros star second baseman Jose Altuve, who's shared a clubhouse with close friend Marwin Gonzalez for the previous seven springs. They became confidants on and off the field, which is what makes this spring so strange.




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Astros open camp with bar 'set incredibly high'

With this many stars and this much talent, you can't help but have visions of playing baseball deep into October. And considering it was only a year ago the Astros were talking about defending their World Series title, their window to win another one remains wide open.




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Cole wins arbitration case vs. Astros

All-Star right-hander Gerrit Cole won his arbitration case against the Astros on Wednesday, meaning he will make $13.5 million this season. The team offerred $11.425 million, a difference of $2,075,000.




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Prospects who should vie for a roster spot

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.




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WATCH: Astros' rotation is ready

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.




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Astros can still win the offseason

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.