Two men were arrested in a fatal shooting in Flint, Mich.

Researchers have built a prosthesis that enabled a man who lost his hand to text, pluck grapes from their stems, and stuff a pillow into its case.

Weeks after the CDC said people should use masks to curb the coronavirus, grocery stores struggle to buy them for staff, partly due to U.S. actions.

He’ll need a better defense than the one his favorite team managed against LSU last year.

Two men were arrested in a fatal shooting in Flint, Mich.

Known for his hearty laugh and creative mind, Storen rose to executive spots in basketball, football, baseball and tennis during a four-decade career in sports.

Lawrence Welk is newly hip at Modernism Week in Palm Springs: The late entertainer's home has been lovingly restored, and is now opening its doors.

Dermalogica, Byredo open in West Hollywood, Gucci adds a rooftop restaurant on Rodeo and Studio C sails into Newport Beach.

The coronavirus outbreak has closed malls and most stores. Disputes are brewing over rent. Retail may look quite different in the future, experts say.

Portland's beloved indie bookstore Powell's Books rehired more than 100 employees after seeing a surge in online orders.

Author James Patterson is donating $500,000 to help indie bookstores across the country. For many L.A. booksellers, that could be a life saver.

Writer turns to guided journal for Michelle Obama's "Becoming" to grapple with anxiety and cabin fever during coronavirus crisis.

Earlier this week, Bookshop.org hit $1 million in earnings that will go to bookstores endangered by the coronavirus outbreak.

Three years after he promised to sell an all-electric Model 3 mass-market sedan for $35,000 before incentives, Elon Musk may finally be coming through.

Confusion and frustration bedevil attempts to keep employees on the job while getting a Payroll Protection Program loan.

"Other Music," "Record Safari" and "Vinyl Nation" offer bittersweet reminders, in a time of coronavirus, of the emotional pull of record stores and vinyl.

Shoppers didn't know it at the time, but their final spree at Amoeba Music's Hollywood store on Sunset Boulevard was their last, as the original location will not reopen.

LEGIONS of gardeners, wondering what has happened to the goods they have bought from online retailer Primrose, are set to receive refunds "within days", the company has confirmed.

From the neighborhood markets to the supermarkets of our past

Check out performances at Indy CD & Vinyl, Luna Music and Square Cat Vinyl.

Many businesses have had to change course during the coronavirus lockdown but few as quickly this e-cig maker who now makes hand sanitizer.

Located off U.S. 36, home decor store At Home will replace what used to be a Gander Mountain in Avon, Indiana.

Grocery stores continue to make changes for the safety of shoppers and employees during the coronavirus pandemic.

Marsh supermarkets that were left vacant in 2017 after the chain's bankruptcy are slowly filling up in the Indianapolis area. Here's how that's benefiting the community.

Here's how grocery stores are trying to accommodate shoppers with new hours, special times for at-risk customers and other changes as of April 29.

More than 22 million Americans are out of work because of how the coronavirus has shut down much of the economy.

Customers ranged from enthusiastic to wary on first day they were able to shop again at suburban Indianapolis malls during the coronavirus pandemic.

Mike Storen, the Pacers' first general manager, former ABA commissioner and the father of ESPN broadcaster Hannah Storm, died Thursday. He was 84.

Dave & Buster's is bringing its restaurant and entertainment complex to Greenwood in April, and the company plans to hire for more than 230 positions.

Check out performances at Indy CD & Vinyl, Luna Music and Square Cat Vinyl.

Mike Storen, the Pacers' first general manager, former ABA commissioner and the father of ESPN broadcaster Hannah Storm, died Thursday. He was 84.

Check out performances at Indy CD & Vinyl, Luna Music and Square Cat Vinyl.

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

Mike Storen, the Pacers' first general manager, former ABA commissioner and the father of ESPN broadcaster Hannah Storm, died Thursday. He was 84.

Some garden centres in the area opened Friday morning with physical distancing measures in place after the provincial government lifted the closures earlier this week.

The Ontario government has given hardware stores leave to reopen, as of Saturday, but the experience for shoppers will not be what it used to be.

The technology giant says it is moving to remote work in order to help reduce the spread of coronavirus.

Shopping for potatoes? Here’s how to know which kind to buy, and the best way to store them.

Continue reading "How to Buy and Store Potatoes" »

Apple, dear reader, has been missing you — and it's banking on the fact that you've been missing the opportunity to touch its products before you buy them, too. 

In an effort to ease this assuredly mutual feeling of longing, the company confirmed on Friday plans to begin reopening some of its U.S. stores as early as MondayApple had been aiming for a May reopening for some time, but now it's official. 

So reports CNBC, which notes that the openings are, for now, limited to stores in four states: Idaho, South Carolina, Alabama, and Alaska.

"We've missed our customers and look forward to offering our support," an Apple spokesperson told CNN Business.  Read more...

The Gothamist is reporting the sad news that Gem Spa, the iconic NY corner store that has been a fixture at St. Marks Place and Second Avenue for around 100 years is being forced to shutter its doors and windows for the last time. The Spa has been struggling to keep up with increasing rent prices and COVID-19 has apparently proven to be the final nail in its coffin.

"It’s where Robert Mapplethorpe bought Patti Smith an egg cream on the day they met. It’s on the back cover of the New York Dolls’ 1973 debut (and where, according to lore, Johnny Thunders and others went for post-heroin sugar fixes between sets at CBGB). Before that, it was where Abbie Hoffman gathered Yippies to rain money on the New York Stock Exchange. It’s where Allen Ginsberg, Ted Berrigan, and other neighborhood poets went to pick up the Sunday New York Times on Saturday nights (and which was inevitably commemorated in their poems)."

Read the rest.

Image: Alex Lozupone, CC BY-SA 4.0 Read the rest

The following article, BREAKING: 43-Yr-Old Father Of 9, Dollar Store Sec Guard, Shot DEAD While Allegedly Trying To Enforce MI Gov Whitmer’s Face Covering Exec Order, was first published on 100PercentFedUp.com.

Will the mainstream media report about the senseless death of a 43-year-old father of nine, who would have been alive today if it were not for VP wannabe, Gretchen Whitmer's executive order that forced him to respond to a customer not wearing a face mask? 

Continue reading: BREAKING: 43-Yr-Old Father Of 9, Dollar Store Sec Guard, Shot DEAD While Allegedly Trying To Enforce MI Gov Whitmer’s Face Covering Exec Order ...

In Lakeshore, it may be a little while longer before a retail cannabis store opens.

At a time when store front vacancies are growing thanks to COVID-19, a new retail cannabis store in Pillette Village is hoping to open soon.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

17 February 2020

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.