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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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Reds' Spring Training opens to a different feel

It wasn't just that there were new faces when Reds camp opened Tuesday with the reporting of pitchers and catchers for physicals, there was a different vibe that could be felt in the hallways and clubhouse.




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Reds may play Lorenzen in OF during spring

Reds reliever Michael Lorenzen's top priority in Spring Training will be to get innings and prepare himself to pitch in what could be a multitude of roles. However, Lorenzen's offseason workouts also included outfield work and batting practice -- and that could continue in the spring.




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Bell leads new-look Reds into Spring Training

As Reds Spring Training opened with pitchers and catchers reporting for physicals on Tuesday, new manager David Bell was already be tasked with many responsibilities. But there will be one that looms largest. Following five years out of the postseason, including the past four with more than 90 losses, Bell must restore a culture of winning.




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Bell lays out vision on first day of workouts

Wednesday marked the first time that manager David Bell got to address Reds players as a group when he spoke to pitchers and catchers ahead of their first workout of Spring Training. Bell put a lot of thought into what he wanted to tell them.




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20 questions that will define the NL Central

It was only five years ago that the Cardinals won the National League Central with only 90 wins. Heck, it was only 12 years ago that the Cubs won it with 85, and 13 that the Cardinals won it with 83. Point is: There have been times in recent baseball history that the NL Central was not exactly the toughest gauntlet in the sport. But in 2019, it looks like the scariest division in baseball.




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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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Bell names likely starting 5, staging 'pen battles

Unlike recent Reds Spring Trainings, much of the drama about who would comprise the rotation was already removed on the first day of camp. That's when manager David Bell revealed the starting five would likely be -- in no particular order -- Sonny Gray, Tanner Roark, Alex Wood, Luis Castillo and Anthony DeSclafani.




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Senzel expected to compete for starting CF gig

As the Reds consider their regular center-fielder options, they are not just humoring career infielder Nick Senzel by letting him compete for the spot. Senzel believes he can do it. Perhaps more importantly, so does new manager David Bell.




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Reds hope Roark will bring stability to rotation

When the Reds overhauled their rotation with three offseason trades, the first deal brought right-hander Tanner Roark from the Nationals for reliever Tanner Rainey. Observers saw Roark as a solid middle-of-the rotation hurler who is steady and dependable while able to rack up innings.




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Reds looking to use Iglesias in variety of ways

The Reds want to use Raisel Iglesias in the most intense moments, even if that means using someone else in the ninth.




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Reasons for optimism for each MLB club

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.




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Rule 5 pick Joe back in catcher's gear with Reds

Utility player and Rule 5 selection Connor Joe has been working with the catchers since Reds Spring Training opened. What makes that a little more interesting is that Joe has never caught a game professionally.




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Reds' Top 30 Prospects list

Who do the Reds have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for Cincy's Top 30 Prospects on MLB Pipeline's Prospect Watch.




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The Reds' 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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Bell facing tough decisions for OF alignment

Reds manager David Bell has great corner outfield depth, but he doesn't have a regular center fielder. Determining who will get to play where and sorting out the log jam should be a challenge for Bell in his first season as a skipper in the big leagues.




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Reds add Dietrich on Minor League deal

Upon the passing of his physical on Tuesday, the Reds signed infielder/outfielder Derek Dietrich to a Minor League contract with an invitation to big league camp for Spring Training.




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Puig ready to take Cincy by storm: 'I love red'

New Reds outfielder Yasiel Puig has been in camp for about a week, often hitting on his own on the backfields. With the first full-squad workout taking place on Monday, Puig was able to warm up, throw and hit with his teammates.




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Winker unfazed by crowded Reds outfield

Since Jesse Winker suffered a season-ending shoulder injury on July 23, he's gained a lot of company in the corner-outfield spots.




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Why can’t vehicle registration be renewed online?

THE EDITOR, Madam: I arrived at the Constant Spring tax office at 6:05 a.m. on Monday, May 4 to renew my vehicle registration. At that hour, there were already 30 persons ahead of me. Persons related horror stories of spending up to five hours in...




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Still not prepared for COVID-19

THE EDITOR, Madam: How many more will have to suffer? How many more will have to die to end the discrimination often meted out to persons suspected of or confirmed with COVID-19? The novel coronavirus is highly contagious, seems so mysterious, and...




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Give children love and appreciation

THE EDITOR, Madam May is Child Month, and we, as parents, would show love and appreciation by taking out our kids for recreation, but instead, we have to keep them indoors because of a bush tiger called coronavirus. Every year at this time, I...




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Letter of the Day | Discrimination and stigma hurt

THE EDITOR, Madam: The devastating news of Jodian Fearon’s death has resulted in public outrage and concern. The controversy and seemingly negligent actions of the hospitals involved have left many Jamaicans anxious about our health system and...




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Private sector should rally with Jamaicans

THE EDITOR, Madam: In times of great challenge and hardship we must continue, as a people, to uphold the values and attitudes that make us truly Jamaican. It is a time for true patriotism and for us to reach down and pull up those among us with...




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Letter of the Day | A toast to great educators

The Editor, Madam: Today, as we celebrate Teachers’ Day, I pause in reflection, looking back at some of the educators who have deeply impacted me. Let me start with the principal of my primary school. She was a God-fearing woman, but I suppose,...




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Re-registration process for persons with disabilities cumbersome

THE EDITOR, Madam: THE JAMAICA Council for Persons with Disabilities (JCPD) – an agency of the Ministry of Labour...




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Safeguard against virus being blamed for everything

THE EDITOR, Madam: COVID-19 can be made to be the blame bearer for every ill, unless careful disaggregation is done to separate what is truly attributable to both its real scope and the understandable ripple effects of the virus. The quality of...




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NIDS would have helped

THE EDITOR, Madam: “WHY CAN’T vehicle registration be renewed online?” That’s the question asked by Dr Rory Dixon, senior medical officer, Sir John Golding Rehabilitation Centre, in his letter to The Gleaner on Tuesday, May 5. The first paragraph...




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Letter of the Day | COVID-19 presents an opportunity for change

THE EDITOR, Madam: THE JAMAICAN economy has been underperforming for the last 40 years, during which economic growth averaged approximately one per cent per annum. One of the main reasons for this poor performance is the non-competitive nature of...




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Letter of the Day | Tap into the cultural gold mine

THE EDITOR, Madam: The Jamaican Government and local private-sector power brokers are still way behind and woefully lacking in investing, financially and otherwise, in Jamaica’s number one most powerful, most famous, most influential, and most...




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Tribute to Prof Fred Hickling

THE EDITOR, Madam: Words cannot describe my feeling of loss on hearing that prominent psychiatrist Professor Fred Hickling has died. Professor Hickling was one of Jamaica’s treasures through his work in the field of community mental health. His...




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What about social rights?

THE EDITOR, Madam: The right to education, decent work, an adequate standard of living, and housing all fall within the realm of economic, social, and cultural rights (ESCRs) guaranteed under the International Covenant on Economic, Social and...




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Scotiabank – a loose vampire

THE EDITOR, Madam: On May 5, 2020, at about 8:40 a.m., I went completely berserk, telling two staff members of the Bank of Nova Scotia from the Liguanea branch some proper Jamaica vernaculars, long like the Holland Bamboo. I was astonished by my...




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Letter of the Day | Tourism won’t be ‘business as usual’

THE EDITOR, Madam: With most things grinding to a halt worldwide, this pandemic has proven to be as much of an economic crisis as it is a health one. Many sectors have changed their day-to-day operations, with some allowing for greater flexibility...




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George Headley Primary creates Peace Garden

A ‘Peace of Paradise’ garden has been created in George Headley Primary School, which is positively affecting behavioural change in students. The garden was created by students, teachers, and members of the community for the 2019 Trees for Peace...




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United against coronavirus through art - Government of India calls artists to participate in a unique art competition

The COVID-19 pandemic around the world has taken the world by storm, touching the lives of every human being on Earth. The global nature of the crisis has united us as human beings and tragedy and deaths in any country by COVID-19 worry us all....




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A refreshing look at personal development and success

At the outset, author Ivy Slater shares the existential crisis that spurred her to change careers. Slater’s psychosocial experience after the passing of her father and the stagnation she experienced at her printing business proved exhaustively...




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Poem fate of the free will

Let’s have heart Let’s have heart And space ourselves Three feet apart Let’s act fast to bring this disease to its last Let’s have heart and play our part To do our best to turn the spread off Hand sanitizers Elbow coughs Masks and...




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A walk down St Catherine’s history

Parish Histories of Jamaica Project, a publication by the JN Foundation in collaboration with the Department of History and Archaeology at The University of the West Indies, Mona, was launched recently. Jenny Jemmott of Department of History and...




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Vodou: fate of the free will Vodou:

Vodou evokes a schizophrenic response among the misinformed. Reactions abound: apprehension, incredulity, and vilification. It is not that Vodou struggles for meaning. Vodou has its own particular ideal. It is primordial sense. It is very much...




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Taking COVID-19 heads on - Student entrepreneurs’ inventions prove viable weapons against deadly virus

As the global battle against the deadly COVID-19 disease wages on, with each country’s government, healthcare industry, and general public playing its part in defeating this new and relatively unknown enemy, two seemingly unlikely foot soldiers...




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Curating the history of a people

Redlining a Holocaust is a rigorously researched oeuvre that establishes Dòwòti Désir as one of the most important figures in contemporary African thought. Redlining is an imaginative and monumental undertaking, a literary, visual, and oratorical...




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Lauren Campbell – basking in shades of creativity

She’s what you’d term the consummate creative – through the sensory ‘dry land tourist’ tales of her ‘Right Roun Di Corna’ blog to the pieces in her JadeLauren eyewear brand, Lauren Campbell is colouring the world with beauty, life, and bomb...




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A pulse of ‘Trinbagonian’ life

The engaging storyline and realness of the characters in Barbara Jenkins’ De Rightest Place makes it a book you breeze through in a matter of days. Set mainly in and around a bar called De Rightest Place, in the environs of a working-class...




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Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide-Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes

Incretin hormone dysregulation contributes to reduced insulin secretion and hyperglycemia in patients with type 2 diabetes mellitus (T2DM). Resistance to glucose-dependent insulinotropic polypeptide (GIP) action may occur through desensitization or downregulation of β-cell GIP receptors (GIP-R). Studies in rodents and cell lines show GIP-R expression can be regulated through peroxisome proliferator–activated receptor (PPAR) response elements (PPREs). Whether this occurs in humans is unknown. To test this, we conducted a randomized, double-blind, placebo-controlled trial of pioglitazone therapy on GIP-mediated insulin secretion and adipocyte GIP-R expression in subjects with well-controlled T2DM. Insulin sensitivity improved, but the insulinotropic effect of infused GIP was unchanged following 12 weeks of pioglitazone treatment. In parallel, we observed increased GIP-R mRNA expression in subcutaneous abdominal adipocytes from subjects treated with pioglitazone. Treatment of cultured human adipocytes with troglitazone increased PPAR binding to GIP-R PPREs. These results show PPAR agonists regulate GIP-R expression through PPREs in human adipocytes, but suggest this mechanism is not important for regulation of the insulinotropic effect of GIP in subjects with T2DM. Because GIP has antilipolytic and lipogenic effects in adipocytes, the increased GIP-R expression may mediate accretion of fat in patients with T2DM treated with PPAR agonists.




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Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels

Fasting hyperinsulinemia precedes the development of type 2 diabetes. However, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence of the progressive increase in fasting glycemia induced by insulin resistance in the prediabetic state. Herein, we have discovered a mechanism that specifically regulates non–glucose-stimulated insulin secretion (NGSIS) in pancreatic islets that is activated by nonesterified free fatty acids, the major fuel used by β-cells during fasting. We show that the mitochondrial permeability transition pore regulator cyclophilin D (CypD) promotes NGSIS, but not glucose-stimulated insulin secretion, by increasing mitochondrial proton leak. Islets from prediabetic obese mice show significantly higher CypD-dependent proton leak and NGSIS compared with lean mice. Proton leak–mediated NGSIS is conserved in human islets and is stimulated by exposure to nonesterified free fatty acids at concentrations observed in obese subjects. Mechanistically, proton leak activates islet NGSIS independently of mitochondrial ATP synthesis but ultimately requires closure of the KATP channel. In summary, we have described a novel nonesterified free fatty acid–stimulated pathway that selectively drives pancreatic islet NGSIS, which may be therapeutically exploited as an alternative way to halt fasting hyperinsulinemia and the progression of type 2 diabetes.




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The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and Is Increased in Type 2 Diabetes and NAFLD/NASH

The BMP2/4 antagonist and novel adipokine Gremlin 1 is highly expressed in human adipose cells and increased in hypertrophic obesity. As a secreted antagonist, it inhibits the effect of BMP2/4 on adipose precursor cell commitment/differentiation. We examined mRNA levels of Gremlin 1 in key target tissues for insulin and also measured tissue and serum levels in several carefully phenotyped human cohorts. Gremlin 1 expression was high in adipose tissue, higher in visceral than in subcutaneous tissue, increased in obesity, and further increased in type 2 diabetes (T2D). A similar high expression was seen in liver biopsies, but expression was considerably lower in skeletal muscles. Serum levels were increased in obesity but most prominently in T2D. Transcriptional activation in both adipose tissue and liver as well as serum levels were strongly associated with markers of insulin resistance in vivo (euglycemic clamps and HOMA of insulin resistance), and the presence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We also found Gremlin 1 to antagonize insulin signaling and action in human primary adipocytes, skeletal muscle, and liver cells. Thus, Gremlin 1 is a novel secreted insulin antagonist and biomarker as well as a potential therapeutic target in obesity and its complications T2D and NAFLD/NASH.




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A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive {beta}-Cell Hyperplasia

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.




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Lipokine 5-PAHSA Is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for De Novo Lipogenesis in Mice

Branched esters of palmitic acid and hydroxystearic acid (PAHSA) are anti-inflammatory and antidiabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the cross talk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using 2H2O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol (TAG)/fatty acid (FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG estolides) in WAT. Utilization of 13C isotope tracers and dynamic metabolomics documented that 5-PAHSA primes adipocytes for glucose metabolism in a different way from insulin, promoting DNL and impeding TAG synthesis. In summary, our data reveal new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA and its relation to insulin action in adipocytes and independently confirm a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis.




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Perivascular Adipose Tissue Controls Insulin-Stimulated Perfusion, Mitochondrial Protein Expression, and Glucose Uptake in Muscle Through Adipomuscular Arterioles

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine," signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.