1. New prime time kings as AFL’s 2025 Thurs night blockbusters revealed  Fox Sports
2. Three Thursday night fixtures revealed  Collingwood
3. What we know about the 2025 fixture: Thursday nights back with a bang, Smith to face Dogs in blockbuster  The Age

1. All-time reaction to coaching ‘disaster’; Steph’s stunning clutch moment: NBA Wrap  Fox Sports
2. Bike rides and Balkan music: Klay Thompson is embracing a fresh start with the Mavericks  ESPN Australia
3. 10 unforgettable Klay Thompson moments with Warriors ahead of return  NBA.com
4. Dub Hub: Warriors players share ‘welcome back’ messages for Klay Thompson’s return  Golden State of Mind

Ski Sunday will be back for the 2011/12 season

UK Sport announces a large investment in British Ski and Snowboarding to be spent in the run-up to the Sochi 2014 Winter Olympics.

The post EA Play: EA Sports FC 24 Joins the Play List This June, As Well as New Rewards appeared first on Xbox Wire.

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There are few stores have game account, they have Xbox account price compare on allkeyshop,

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EA SPORTS FC 24 Standard Edition for PS4 PS5 Account $42.21

This is the Call for Nominations for the 2020 Theszie Awards (the rec.sport.pro-wrestling Awards). To nominate candidates for all categories, you may use this form. Nominations are due by January 3, 2021. Finally, to see previous years’ results, click here for 2019, here for 2018, here for 2017, here for 2016, here for 2015, here […]

(Sorry for the delay: we had a record number of nominations to plow through – over 250 in most categories!) This is the Call for Votes for the 2020 RSPW (Theszie) Awards. You can vote here. The Theszies are the oldest fan awards in pro wrestling history, going back to 1990 (when Mr. Perfect quite […]

This is the Call for Nominations for the 2021 Theszie Awards (the rec.sport.pro-wrestling Awards). (Look, I started a new job late last year and my December was slammed. Sorry for the delay.) To nominate candidates for all categories, you may use this form. Nominations are due by January 28, 2021. Finally, to see previous years’ […]

This is the Call for Votes for Wait wait wait wait wait. It’s May. You see, May first is International Workers’ Day, and wrestlers are workers, as we all know, so – Not buying that. Well, we were trying to build this new site, and then decided not to do it, and then someone’s work […]

Charles (Charlie) Tennyson has been appointed Princeton’s new director of Transportation and Parking Services following a national search to fill the position. He previously served for five years as deputy director of the department.

2024 was a banner year for the cross-country riders on Team USA.
( Photos: 5, Comments: 40 )

Here’s how cannabis use became prohibited—and the science of its biological, psychological, and social effects.

Sam Koch looked like he was playing very, very badly. In fact, he was changing one of sport's strangest positions for ever.

A selection of some of the most striking sports photographs taken around the world over the past seven days.

30% of Americans have passports. But where do those Americans live? New Jersey takes the prize for the highest percentage of passports issued: 68.36%. At the low end: Mississippi, with just 19.86%. Via C.G.P. Grey, see the graphic below: For the “yes, but…” file: This dataset actually reflects addresses for issuance, not ownership of US […]

Springbok coach Rassie Erasmus wants a tour whitewash and, with the Scotland win, he's a third of the way there. He didn't say it would be pretty, as Sunday's success at Murrayfield showed.

With some of its infrastructure decaying and no premier division club using it, the somewhat abandoned Dobsonville Stadium offered the perfect setting for Sage Stephens to take his first steps as a Bafana Bafana player at the ripe age of 33.

The rare feat of winning both the Two Oceans and Soweto marathons has marked Onalenna Khonkhobe’s breakthrough season, establishing him as one of South Africa’s rising road-running stars.

Canan Moodie used his start against Scotland to show that he is about far more than just pace out wide and aerial ability.

Sir Kenny Dalglish hailed nine-time Major champion Gary Player and expressed his delight at Liverpool's position at the top of the Premier League during his visit to South Africa this weekend.

In his latest Rucking with Rob newsletter, Rob Houwing argues that for England to have any hopes of beating the Springboks, they'll have to be on the ball in the final stages.

Sri Lanka's cricket board named former South African batsman Neil McKenzie as a consultant coach ahead of their Test tour of South Africa.

As captain, Aiden Markram is allowed a long rope from a wonky form perspective, but how long can that rope be as the run river continues to shrivel, asks Khanyiso Tshwaku.

Proteas all-rounder Marco Jansen, while acknowledging that spin has been a challenge for them in the ongoing T20 series against India, reckons things could be a bit different for Wednesday's third T20 in Centurion.

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season.

The Springboks will continue to evolve their attack, but they must do so within the framework of what has made them so successful, says attack coach Tony Brown.

Jannik Sinner hit the accelerator at the end of each set as he cruised past Taylor Fritz 6-4, 6-4 on Tuesday to close in on a semi-final spot at the ATP Finals in Turin.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

The first battle cry has sounded ahead of the showdown at Twickenham on Saturday, with English winger Tommy Freeman reckoning that the Springboks are 'still human' and 'still playing the same game'.

Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium.

Wednesday's third T20 between South Africa and India at SuperSport Park in Centurion is shaping up to be a run-drenched one, especially if the weather holds and SA's bowling centre doesn't.

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.

Late injection Johan Grobbelaar may find himself more than simply an “extra” on the Bok tour, writes Rob Houwing.

Springbok team doctor Jerome Mampane says that injured utility back Sacha Feinberg-Mngomezulu is recovering well.

It sounds like an oxymoron: “How to keep blood-sports interesting?” You’ve got blood and you’ve got sports, the term does its own advertising! And yet, fighting promotions rise and fall, where Pride and Strikeforce once reigned, now stand One and Bellator, but one promotion stands above all its competitors. The world of MMA knows one promotion which has clawed its way to the international top and established itself as the gold standard upon whose hallowed surface skulls are crushed and blood is poured. I’m talking about none other than the UFC.

Having established itself over the years as a beacon of both quality matches and consistent drama, the UFC attracts the lion’s share of international talent in the MMA world, and with it the eyes and ears of MMA fans everywhere. Having well and truly stroked the ego of the promotion, you might be wondering what on earth any of this has to do with writing or fantasy?

Well, does your world happen to feature prizefighting, ritual combat, or the eternally popular fantasy fixture called the gladiatorial arena? If so, there are a lot of writing and worldbuilding lessons you can learn from observing the biggest promotion in the biggest modern blood-sport of the world.

Continue reading Lessons from the UFC: How to Keep Blood-Sports Interesting at Mythic Scribes.

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations.

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles

Nonsmall cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. While mutations in Kras and overexpression of Myc are commonly found in patients, the role of altered lipid metabolism in lung cancer and its interplay with oncogenic Myc is poorly understood. Here we use a transgenic mouse model of Kras-driven lung adenocarcinoma with reversible activation of Myc combined with surface analysis lipid profiling of lung tumors and transcriptomics to study the effect of Myc activity on cholesterol homeostasis. Our findings reveal that the activation of Myc leads to the accumulation of cholesteryl esters (CEs) stored in lipid droplets. Subsequent Myc deactivation leads to further increases in CEs, in contrast to tumors in which Myc was never activated. Gene expression analysis linked cholesterol transport and storage pathways to Myc activity. Our results suggest that increased Myc activity is associated with increased cholesterol influx, reduced efflux, and accumulation of CE-rich lipid droplets in lung tumors. Targeting cholesterol homeostasis is proposed as a promising avenue to explore for novel treatments of lung cancer, with diagnostic and stratification potential in human NSCLC.

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1^+/+ and Abca1^–/– mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

The organic anion transporters (OATs) and organic anion–transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.

SLC19A2 and SLC19A3, also known as thiamine transporters (THTR) 1 and 2, respectively, transport the positively charged thiamine (vitamin B1) into cells to enable its efficient utilization. SLC19A2 and SLC19A3 are also known to transport structurally unrelated cationic drugs, such as metformin, but whether this charge selectivity extends to other molecules, such as pyridoxine (vitamin B6), is unknown. We tested this possibility using Madin-Darby canine kidney II (MDCKII) cells and human embryonic kidney 293 (HEK293) cells for transfection experiments, and also using Caco-2 cells as human intestinal epithelial model cells. The stable expression of SLC19A2 and SLC19A3 in MDCKII cells (as well as their transient expression in HEK293 cells) led to a significant induction in pyridoxine uptake at pH 5.5 compared with control cells. The induced uptake was pH-dependent, favoring acidic conditions over neutral to basic conditions, and protonophore-sensitive. It was saturable as a function of pyridoxine concentration, with an apparent Km of 37.8 and 18.5 μm, for SLC19A2 and SLC19A3, respectively, and inhibited by the pyridoxine analogs pyridoxal and pyridoxamine as well as thiamine. We also found that silencing the endogenous SLC19A3, but not SLC19A2, of Caco-2 cells with gene-specific siRNAs lead to a significant reduction in carrier-mediated pyridoxine uptake. These results show that SLC19A2 and SLC19A3 are capable of recognizing/transporting pyridoxine, favoring acidic conditions for operation, and suggest a possible role for these transporters in pyridoxine transport mainly in tissues with an acidic environment like the small intestine, which has an acidic surface microclimate.

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.