The Indianapolis Colts select Washington State wide receiver Dezmon Patmon with the 212th pick.

Wilson flashed promise in Year 2 after being a second-round pick but was benched last season

The Colts' sixth-round pick is trying to catch the attention of actress Zendaya

After his name popped up in trade rumors the Colts spent a third-round pick on a safety. Are the Colts preparing for a future without Malik Hooker?

Colts legend Robert Mathis rebuilt Kemoko Turay into a tactical, calculated missile instead of a grenade lobbed into the dark.

Simon Stepaniak started 31 games for the Indiana Hoosiers, mostly at guard; that's the second year in a row an IU guard was picked.

The sports bar and restaurant owned by former Colts football player and Super Bowl champion Gary Brackett is closing.

Tight end who scored 16 touchdowns for the Boilermakers is picked by the Los Angeles Rams in the fourth round.

After England's 2-1 T20 series win in South Africa, pick your team for the opening T20 World Cup game in October.

Who would you select in an all-time Indian Premier League XI?

California's tepid reopening amid the coronavirus sparked a mix of excitement, confusion and uncertainty.

Here's how the new Turner Classic Movies "Essentials" guest — the man behind "The Incredibles" and "Ratatouille" — has been influenced by Hitchcock, '50s sci-fi and James Bond.

New England has a negative point differential heading into Week 4 for the first time since 2008.

Contrarian bettors are off to their best start through the first four weeks of the season since 2003.

Cam Newton is 4-0 against the Redskins, with 11 touchdowns (nine passing, two rushing) and zero interceptions for his career.

Goff is using play-action more often than any other quarterback in 2018.

Giants' offensive line is allowing an adjusted sack rate of over eight percent, the eighth-worst in the NFL.

According to Football Outsiders, Atlanta has the second-worst defense this season after adjusting its performance for strength of schedule.

Pittsburgh has had trouble with the strengths of Carolina's offense.

Since 2002, the year the league expanded to 32 teams, favorites playing on Thanksgiving are 28-12 against the spread.

The Baltimore defense has produced a very effective pass rush lately.

From 2003 to 2017, underdogs getting seven points or more at home were 94-72-1 overall against the spread and that includes a 43-26-1 ATS record in December and January.

The 49ers are 1-9 straight up in their last 10 divisional games.

Alabama and Clemson appear to be on a collision course ending at the College Football Playoff championship game on Jan. 7 at Levi’s Stadium.

It hasn't been a great year for road favorites. Those who enjoyed a three-point advantage or more on the road have gone 21-30-2 against the spread.

She has apparently tricked the president into thinking she supports his fiscal ideas. Her actual ideas are worse.

Judy Shelton is an opportunist and a quack. Senate Republicans seem to know this — but they still may be too craven to oppose her nomination.

oscon: High Availability in MySQL - how to pick a solution that best matches your use case http://t.co/PItdw0maTj @h_ingo #oscon #tutorial

Teacher question: You wrote recently that it was a good idea to teach comprehension skills, but our school district says we shouldn’t, that it’s prior knowledge that matters. Do you know the baseball study? Have you read Natalie Wexler’s research? It is really difficult to trust research when everyone tells us something different. Shanahan's response:  I feel your pain.

Teacher question: You wrote recently that it was a good idea to teach comprehension skills, but our school district says we shouldn’t, that it’s prior knowledge that matters. Do you know the baseball study? Have you read Natalie Wexler’s research? It is really difficult to trust research when everyone tells us something different. Shanahan's response:  I feel your pain.

An organized kitchen doesn't have to be super minimal; it just has to function well. These editor-approved kitchen organizers help make the tools and ingredients in your kitchen more visible and accessible, so you can cook with more ease and joy!

Continue reading "Editors’ Picks: Kitchen Organizers" »

RCMP say a 50-year-old man died and a 60-year-old man is in hospital following a crash involving a CP Rail train Friday morning.

Inês Magro dos Reis
Apr 14, 2020; 0:jlr.RA120000632v1-jlr.RA120000632
Research Articles

Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1^nih), creating a dysfunctional NPC1 protein. Npc1^nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1^nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1^nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.

Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder in which cholesterol and glycosphingolipids accumulate in late endosomal/lysosomal compartments because of mutations in the NPC1 gene. A hallmark of NPC1 is progressive neurodegeneration of the cerebellum as well as visceral organ damage; however, the mechanisms driving this disease pathology are not fully understood. Phosphoinositides are phospholipids that play distinct roles in signal transduction and vesicle trafficking. Here, we utilized consensus spectra analysis of MS imaging datasets and orthogonal LC–MS analyses to evaluate the spatial distribution of phosphoinositides and quantify them in cerebellar tissue from Npc1-null mice. Our results suggest significant depletion of multiple phosphoinositide species, including phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and bisphosphate (PIP2), in the cerebellum of the Npc1-null mice in both whole-tissue lysates and myelin-enriched fractions. Additionally, we observed altered levels of the regulatory enzyme phosphatidylinositol 4-kinase type 2 α (PI4K2A) in Npc1-null mice. In contrast, the levels of related kinases, phosphatases, and transfer proteins were unaltered in the Npc1-null mouse model as observed by Western blot analysis. Our discovery of phosphoinositide lipid biomarkers for NPC1 opens new perspectives on the pathophysiology underlying this fatal neurodegenerative disease.

Niemann-Pick disease type C (NPC) disease is a lipid-storage disorder that is caused by mutations in the genes encoding NPC proteins and results in lysosomal cholesterol accumulation. 2-Hydroxypropyl-β-cyclodextrin (CD) has been shown to reduce lysosomal cholesterol levels and enhance sterol homeostatic responses, but CD’s mechanism of action remains unknown. Recent work provides evidence that CD stimulates lysosomal exocytosis, raising the possibility that lysosomal cholesterol is released in exosomes. However, therapeutic concentrations of CD do not alter total cellular cholesterol, and cholesterol homeostatic responses at the ER are most consistent with increased ER membrane cholesterol. To address these disparate findings, here we used stable isotope labeling to track the movement of lipoprotein cholesterol cargo in response to CD in NPC1-deficient U2OS cells. Although released cholesterol was detectable, it was not associated with extracellular vesicles. Rather, we demonstrate that lysosomal cholesterol trafficks to the plasma membrane (PM), where it exchanges with lipoprotein-bound cholesterol in a CD-dependent manner. We found that in the absence of suitable extracellular cholesterol acceptors, cholesterol exchange is abrogated, cholesterol accumulates in the PM, and reesterification at the ER is increased. These results support a model in which CD promotes intracellular redistribution of lysosomal cholesterol, but not cholesterol exocytosis or efflux, during the restoration of cholesterol homeostatic responses.

Many chemicals and cellular processes cause oxidative stress that can damage lipids, proteins, or DNA (1). To quickly sense and respond to this ubiquitous threat, organisms have evolved enzymes that neutralize harmful oxidants such as reactive oxygen species and electrophilic compounds (including xenobiotics and their breakdown products) in cells.These antioxidant enzymes include GSH S-transferase (GST),2 NADPH:quinone oxidoreductase 1, thioredoxin, hemeoxygenase-1, and others (2, 3). Many of these proteins are commonly expressed in cells exposed to oxidative stress.The antioxidant response element (ARE) is a major regulatory component of this cellular stress response. The ARE is a conserved, 11-nucleotide-long DNA motif present in the 5'-flanking regions of many genes encoding antioxidant proteins. The laboratory of Cecil Pickett (Fig. 1) at the Merck Frosst Centre for Therapeutic Research in Quebec discovered ARE, a finding reported in the early 1990s in two JBC papers recognized as Classics here (4, 5).jbc;295/12/3929/F1F1F1Figure 1.Cecil Pickett (pictured) and colleagues first described the ARE motif, present in the 5' regions of many genes whose expression is up-regulated by oxidative stress and xenobiotics. Photo courtesy of Cecil Pickett.ARE's discovery was spurred in large part by Pickett's career choice. After completing a PhD in biology and a 2-year postdoc at UCLA in the mid-1970s, he began to work in the pharmaceutical industry.Recruited to Merck in 1978 by its then head of research and development (and later CEO), Roy Vagelos, “I became interested in how drug-metabolizing enzymes were induced by various xenobiotics,” Pickett says.According to Pickett, Vagelos encouraged researchers at the company...

This week, junior doctors in England have taken industrial action for the second time in as many months after failing to reach agreement with the government over their proposed new contract. Tom Moberley and Abi Rimmer, from BMJ Careers, went to the picket lines at Northwick Park Hospital, and University Hospital Lewisham to talk to the doctors,...

If you’re lucky enough to not be back at work, you might be feeling like you need to quickly refresh your medical knowledge - and this podcast the BMJ’s education editors take you on a whistlestop tour through the BMJ’s education articles of 2019. Tom Nolan (GP in London) is joined by Navjoyt Ladher (GP in London), Anita Jain (GP in India) and...

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.

The Dallas Cowboys agreed to terms with free-agent offensive lineman Cameron Erving, the team announced Wednesday.

Former Auburn defensive tackle Derrick Brown agreed to his rookie contract with the Carolina Panthers on Friday.

They don’t stand on one leg around just anybody but often prefer certain members of the flock.

-- Read more on ScientificAmerican.com

Some years ago, a political scientist conducted an interesting experiment that speaks to the fractured race for the Republican presidential nomination, which now has six candidates, five issues, and four potential front-runners.

Turn new season cherries into an exotic condiment. These make an elegant accompaniment to pates, terrines, baked ham, roast quail, cheese boards, or serve on antipasto platters to accompany charcuterie or any smoked or cured meats. Add them to a salad containing smoked chicken.

Fresh, bright and delicious.

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of David Hall of Pure South Dining.

Delicious gourmet steak, onion and cheese sandwich