After joining social media site TikTok to tackle the challenge, the leading man in'The Two Popes' passes it on to action stars Sylvester Stallone and Arnold Schwarzenegger.

After joining social media site TikTok to tackle the challenge, the leading man in'The Two Popes' passes it on to action stars Sylvester Stallone and Arnold Schwarzenegger.

INTRO – If you like your country or acoustic music slick and highly produced, don’t buy the following CD by Raleigh’s Lynda Dawson and Greenville’s Pattie Hopkins. One guitar, one fiddle, two voices … that’s it … and the CD’s title tells you everything you need to know about the music inside. George Olsen talked with Lynda & Pattie and has this. When I receive music in the mail the first thing I might notice is the CDs title. In the case of Lynda Dawson & Pattie Hopkins CD “Traditional Duets” the first thing that popped into my head was “they certainly didn’t expend a lot of energy naming this disc.” After listening to the disc my review changed to “great music, boring name.” Boring or not, Lynda & Pattie somehow stumbled upon a perfectly descriptive title for their CD that somehow after centuries of traditional music is absolutely unique. (PH) “Traditional Duets was actually a place holder with our graphic design artist and toward the end of the project we fell in love

Amazon’s India unit has contracted 2 million sq ft while Walmart-backed Flipkart has contracted 1 million sq ft across Bengaluru, Mumbai Metropolitan Region, Hyderabad, Pune, Ahmedabad, Lucknow and Coimbatore, said multiple persons aware of the development.

Sources in the company said, McNeal’s role will now be divided between Sriram Venkataraman, who is expected to take over as the CFO of Flipkart as well as the fashion etailer Myntra, and Adarsh Nahata who is currently PhonePe’s CFO.

In his new role, Venkataraman will be responsible for key finance operations and functions at Flipkart and Myntra, including Tax, Risk Management, and Treasury.

The Walmart-owned company said it had seen an increase in searches for consumer electronic products, including personal grooming equipment such as trimmers.

The startup, backed by Ratan Tata's investment platform RNT Capital, confirmed his appointment.

Brückenteilzeit heißt das neue Schlupfloch, das Privatversicherten den Wechsel in die gesetzliche Krankenversicherung ermöglicht. Die Flucht aus dem teuren PKV-Tarif funktioniert unter ganz bestimmten Bedingungen.

Viele Privatversicherte bereuen ihren Eintritt in die PKV und suchen nach einer Möglichkeit, sie wieder zu verlassen. Normalerweise ist das extrem schwierig. Doch die Corona-Krise ermöglicht einen solchen Exit. WELT erklärt, wer jetzt die Chance dazu hat.

Slipknot is a Grammy-winning metal band from Des Moines, Iowa, who first formed in 1995. They’ve sold over 30 million records. In this episode, guitarist Jim Root breaks down how Slipknot made the song, “Unsainted,” from their 2019 album We Are Not Your Kind.

songexploder.net/slipknot

Quade Green is expected to start for Washington in Friday's regular-season opener against No. 16 Baylor.

Washington State star CJ Elleby, a former Cleveland High star, is averaging 21.6 points and eight rebounds during three games against Washington. He torched the Huskies for a career-high 34 points in their last meeting while tallying 26 during his previous visit Alaska Airlines Arena.

Sorell farmer Shane Newitt put six months of love into his giant pumpkin to compete at the Bream Creek Show, but its cancellation hasn't stopped him showing it off.

Farmers in Western Australia's far north have carved a spot in the niche Halloween pumpkin market growing in popularity around the country.

A man in his 40s is in a critical condition, and four people are on the run, after a "horrific" stabbing in a convenience store on the NSW Central Coast.

(California Court of Appeal) - Affirmed order denying anti-SLAPP motion. Plaintiffs sought to assign leasehold interest in shopping center. Defendant refused to consent to assignment. Plaintiff brought suit alleging Defendant improperly withheld assignment. Defendant brought an anti-SLAPP motion which the trial court denied because the assignment request was not a settlement communication or litigation-related conduct.

The season is here, and the pumpkins are cuter than ever.

Bojíte se, že letos nebudete zatlačovat slzu u zlatavých nekonečných obzorů? Ale budete. A mnozí alergici na řepku slzy zatlačují už teď. Rajčata stojí sice 170kč za kilo, květák je už také kaviárem českých domácností, ale heslo "řídit stát jako zemědělství" nám zajistilo širé moře zlaté barvy. Sice se z řepky nenajíme (teda až na ty, co z pěstování rýžují zlaté dotace), ale že jsou to panorámata, co? 

Pumpkin Scones perfect for morning or afternoon tea. Full of flavours that the kids will certainly love.

craving more? check out TasteSpotting

Гитарист SLIPKNOT Jim Root в недавнем интервью рассказал о том, что использует время на карантине для сбора идей для возможного сольного альбома:

«Теперь, когда мы переживаем эту безумную пандемию, я пытаюсь заставить себя писать.

Многие люди спрашивали меня о создании сольного проекта, и сейчас, думаю, у меня появилось дополнительное время, которое я могу ему посвятить. Я уже некоторое время сочиняю материал, который, возможно, не впишется в привычное творчество SLIPKNOT. Но в настоящее время я испытываю что-то вроде творческого кризиса.

Мне бы хотелось запустить соло-проект, потому что я хочу заниматься делом. У меня нет семьи, я никогда не был женат. И мне известно, что Corey (фронтмен SLIPKNOT) упоминал о желании сделать сольный проект вне STONE SOUR. И если бы я не писал для SLIPKNOT, я бы не знал, куда девать своё время.

Мне легко сочинять аранжировки и идеи для SLIPKNOT — они для меня естественны, просто потому, что я провёл очень много времени с (покойным басистом SLIPKNOT) Paul'ом Grey'ем. Когда пишешь столь много, сколько я написал для последних двух альбомов, особо задумываться не приходится. Но для сольного проекта я собираюсь думать до тех пор, пока с ума не сойду, поэтому, быть может, этот материал вообще никогда не выйдет.

Это один из тех случаев, когда ты задаёшься вопросом вроде: "И в каком направлении я иду? Я вообще думал о направлении?" Позволю ли я вещам просто случиться естественным образом? Буду ли использовать те наработки, которые создавались для SLIPKNOT, но к которым SLIPKNOT вовсе не стремятся и считают их не очень-то подходящими для группы? Не то чтобы существовали правила насчёт того, что можно считать SLIPKNOT’овским, а что нет. Хорошая песня есть хорошая песня, кому бы она ни предназначалась.

Разумеется, SLIPKNOT — это мой приоритет навсегда. Я буду фокусироваться на группе, как только смогу, пока команда жизнеспособна, пока все мы пожелаем продолжать совместную работу.

Что я сделаю в рамках сольного проекта? В каком направлении двинусь? Думаю, это естественным образом вытекает из всех аранжировок, которые я сделал для последних двух записей SLIPKNOT. Не знаю, нужен ли мне другой механизм творческого самовыражения. Но я намерен постараться — поставить цель и посмотреть, смогу ли я её достигнуть. Времени у нас теперь предостаточно». #Slipknot #Metal #_Metal #AlternativeMetal #Alternative_Metal #NuMetal #Nu_Metal

• 1 cup carrots, cut into chunks
• 1 banana, sliced and frozen
• 1 cup almond milk 
• 1 teaspoon cinnamon
• 1/2 teaspoon ginger
• 1/4 teaspoon allspice
• pinch nutmeg
• 1/2 cup chopped dates
• 1/4 cup chopped pecans or other nuts
• 1 cup chopped apples

1. In a high powered blender, puree the carrots, banana, and almond milk until very smooth.
2. Add in the cinnamon, ginger, allspice, and nutmeg and pulse a few times to blend well.
3. Pour into a bowl and add the chopped dates, pecans, and apples. A sprinkle of coconut flakes goes well, too!

1. Flipkart teases the release of iPhone SE (2020) in India  NewsBytes
2. Apple iPhone SE 2020 sale to start soon as Flipkart teaser goes live  Hindustan Times
3. Apple iPhone SE 2020 spotted on Flipkart, launch imminent  Livemint
4. Our Apple iPhone SE (2020) video review is up - GSMArena.com news  GSMArena.com
5. Excited for the new iPhone? Take our iPhone through the ages quiz  Techradar
6. View Full coverage on Google News

It’s fine to do this for experiments, but for BGP route filtering?

The sprawling Baltimore County home once inhabited by Orioles stars Cal Ripken Jr. and Adam Jones is back on the market after less than six months.

Casting himself as being a sinner on borrowed time, 'Two Popes' actor Anthony Hopkins has one rule for life: Be kind.

Brooks Koepka admits talking smack with Michael Jordan backfired on the golf course.

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

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon/insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion under limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon/insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver.

Michael Plank
Apr 1, 2020; 19:655-671
Research

Adenosine monophosphate-activated protein kinase (AMPK) is an obligate heterotrimer that consists of a catalytic subunit (α) and two regulatory subunits (β and ). AMPK is a key enzyme in the regulation of cellular energy homeostasis. It has been well studied and is known to function in many cellular pathways. However, the interactome of AMPK has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we used tandem-affinity purification, coupled with mass spectrometry (TAP-MS) analysis, to determine the interactome of AMPK and its functions. We conducted a TAP-MS analysis of all seven AMPK subunits. We identified 138 candidate high-confidence interacting proteins (HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complexes. Five candidate AMPK-binding proteins were experimentally validated, underlining the reliability of our data set. Furthermore, we demonstrated that AMPK acts with a strong AMPK-binding protein, Artemis, in non-homologous end joining. Collectively, our study established the first AMPK interactome and uncovered a new function of AMPK in DNA repair.

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases.

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon/insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion under limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon/insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver.

Obesity, dyslipidemia, and insulin resistance, the increasingly common metabolic syndrome, are risk factors for CVD and type 2 diabetes that warrant novel therapeutic interventions. The flavonoid nobiletin displays potent lipid-lowering and insulin-sensitizing properties in mice with metabolic dysfunction. However, the mechanisms by which nobiletin mediates metabolic protection are not clearly established. The central role of AMP-activated protein kinase (AMPK) as an energy sensor suggests that AMPK is a target of nobiletin. We tested the hypothesis that metabolic protection by nobiletin required phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in mouse hepatocytes, in mice deficient in hepatic AMPK (Ampkβ1^–/–), in mice incapable of inhibitory phosphorylation of ACC (AccDKI), and in mice with adipocyte-specific AMPK deficiency (iβ1β2AKO). We fed mice a high-fat/high-cholesterol diet with or without nobiletin. Nobiletin increased phosphorylation of AMPK and ACC in primary mouse hepatocytes, which was associated with increased FA oxidation and attenuated FA synthesis. Despite loss of ACC phosphorylation in Ampkβ1^–/– hepatocytes, nobiletin suppressed FA synthesis and enhanced FA oxidation. Acute injection of nobiletin into mice did not increase phosphorylation of either AMPK or ACC in liver. In mice fed a high-fat diet, nobiletin robustly prevented obesity, hepatic steatosis, dyslipidemia, and insulin resistance, and it improved energy expenditure in Ampkβ1^–/–, AccDKI, and iβ1β2AKO mice to the same extent as in WT controls. Thus, the beneficial metabolic effects of nobiletin in vivo are conferred independently of hepatic or adipocyte AMPK activation. These studies further underscore the therapeutic potential of nobiletin and begin to clarify possible mechanisms.

Sodium glucose co-transporter-2 inhibitors (SGLT2i) have favorable cardiovascular outcomes in diabetic patients. However, whether SGLT2i can improve obesity-related cardiac dysfunction is unknown. Sestrin2 is a novel stress-inducible protein that regulates AMPK-mTOR and suppresses oxidative damage. The aim of this study was to determine whether empagliflozin (EMPA) improves obesity-related cardiac dysfunction via regulating Sestrin2-mediated pathways in diet-induced obesity. C57BL/6J mice and Sestrin2 knockout mice were fed a high-fat diet (HFD) for 12 weeks and then treated with or without EMPA (10 mg/kg) for 8 weeks. Treating HFD-fed C57BL/6J mice with EMPA reduced body weight, whole-body fat, and improved metabolic disorders. Furthermore, EMPA improved myocardial hypertrophy/fibrosis and cardiac function, and reduced cardiac fat accumulation and mitochondria injury. Additionally, EMPA significantly augmented Sestrin2 levels, increased AMPK and eNOS phosphorylation, but inhibited Akt and mTOR phosphorylation. These beneficial effects were partially attenuated in HFD-fed Sestrin2 knockout mice. Intriguingly, EMPA treatment enhanced the Nrf2/HO-1-mediated oxidative stress response, suggesting antioxidant and anti-inflammatory activity. Thus, EMPA improved obesity-related cardiac dysfunction via regulating Sestrin2-mediated AMPK-mTOR signaling and maintaining redox homeostasis. These findings provide a novel mechanism for the cardiovascular protection of SGLT2i in obesity.

D. Grahame Hardie
Jul 1, 2013; 62:2164-2172
Perspectives in Diabetes

PGA Tour star Brooks Koepka said he'll no longer smack talk Michael Jordan on the golf course after he lost a round to the basketball legend.

Johns Hopkins University will start two clinical trials of convalescent blood plasma for treatment of COVID-19, the disease caused by the new coronavirus.

Pumpkin soup on it's own can be rather plain but with interesting garnishes, the ordinary becomes delicious. This variation on a classic pesto, which uses pine nuts, incorporates roasted almonds instead, giving this ubiquitous winter soup a greater depth of flavour and crunch.

A spicey version of a winter favourite

I have clear memories of being about four year's old standing on a little stool next to my mum while she made batches of these golden scones. I always loved being in the kitchen with her and she was endlessly patient, letting me help mix, stir, roll and shape all manner of things (in this case turning a blind eye when I smuggled little nuggets raw dough and dates into my mouth.) We would chat away as we went and she would explain to me what she was doing. I remember to this day her telling me the secret to making good scones was to use the lightest touch possible when you're mixing the dough together...we had no food processor then so everything was mixed by hand and I loved rubbing the flour and butter together, lifting my hands high as she had taught me to help keep the scones light. Although I whiz these up in a processor now, every so often I make a batch by hand, and am immediately whisked back into that childhood kitchen and can almost feel and see Cooee, my mum, beside me in her wonderful cinch-waisted 60's polka dot dress...it's a wonderful image.

1.2kg butternut pumpkin, peeled, cut into 2cm pieces 2 tablespoons olive oil 1 tablespoon chopped fresh sage, plus 12 whole leaves to serve 1/4 teaspoon freshly grated nutmeg 350g ricotta 1 egg 1 cup grated parmesan, plus extra to serve 8 fresh lasagne sheets 100g unsalted butter 2 tablespoons chopped walnuts