Amy’s Kitchen is recalling Gluten Free Vegetable Lasagne because the packs may contain metal shavings.

Unilever is recalling Wall’s Mini Calippo (Orange and Lemon-Lime) multi-packs because they may contain small pieces of metal. The presence of metal makes this product unsafe to eat.

A statement from Arsenal on Thursday night revealed that the manager had contracted the disease after starting to feel ill.

Evangelos Marinakis is recovering from coronavirus two weeks after announcing his diagnosis.

Five-year study improves understanding of impact of foodborne illnesses and strengthens the Food Standards Agency’s ability to respond to them.

EXCLUSIVE: Wales rugby star George North is about to become a father during the coronavirus.

GRANT SHAPPS announced the Government is introducing a £2 billion travel scheme to encourage Britons to use alternative transport as the UK slowly relaxes lockdown measures.

TESCO, Asda, Sainsbury's and Waitrose customers are among those being warned of an urgent product recall, because an item which has been sold by the aforementioned retailers is at risk of potentially containing small pieces of metal.

Unai Emery has identified the player that could be vital in Arsenal's Premier League top-four push.

These discs address the issues with the default network manager configuration as well as an issue with Bodhi Builder not adding the Bodhi 5 repos by default on installed systems. Bodhi 5.0.0 Beta Disc...

WE CHECK in to a mansion fit for foodies and sports lovers.

THERE'S a little village in Cornwall that's making all the right movies. And it's not Port Isaac, which is rightly famous for ITV's Doc Martin and BBC's period drama Poldark. No, this is Portloe, which can lay claim to being the forerunner when, back in 1949, Disney chose the tiny fishing village to film scenes for its celluloid masterpiece Treasure Island.

Zion National Park officials announced this weekend the park will be reopening May 13 "certain areas" of the park. Here's what that means.

IndyCar will host its season-opener at Texas Motor Speedway on June 6 as planned, but without fans and in a one-day show.

Passagem da Terra pela trilha de resquícios do cometa Halley traz espetáculo de chuva de meteoros todos os anos; países da América do Sul estão entre os melhores posicionados para assistir a esse show noturno.

A fixture in IU's starting lineup for most of the past two years, Smith averaged 10.4 points and 5.2 rebounds per game in 2019-20.

A fixture in IU's starting lineup for most of the past two years, Smith averaged 10.4 points and 5.2 rebounds per game in 2019-20.

Simon Property Group plans to reopen on Saturday Indiana malls shuttered during the coronavirus pandemic, according to a leaked internal memo.

Indiana is reopening its economy after its coronavirus closures. Here's what shoppers should know about how malls, stores, salons and gyms will return

You can have a sneak preview at the new Tripadvisor site by browsing this “beta” microsite that TA globally announced today in its newsletter. The user-generated reviews’ giant Tripavisor (part of the Expedia, Inc. family of travel companies), decided to “create a new and easier to use” site. Kristen Nicole from Mashable previously published an article [...]

It comes after reports that garden centres in England and Wales are set to reopen.

Documents obtained from state Treasurer Fiona Ma's office through a records request include an invoice from a BYD subsidiary for 'N95 face masks.'

IndyCar will host its season-opener at Texas Motor Speedway on June 6 as planned, but without fans and in a one-day show.

Israel's PM has turned his chief challenger, Benny Gantz, into his chief deputy, writes Tom Bateman.

New documents reveal the "strongest evidence yet" of China's crackdown on people in Xinjiang.

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.

1. Ahmedabad Police Detain 4 for Spreading Rumours on Amit Shah's Health  The Wire
2. I am healthy, not suffering from any disease, says Amit Shah  Times of India
3. HM Amit Shah silences all the rumour mongers, says 'No need to worry'  TIMES NOW
4. Not Allowing Migrants' Trains "Injustice": Amit Shah To Mamata Banerjee  NDTV
5. 'Not Suffering From Any Disease': Amit Shah Dismisses Rumours About His Health  Outlook India
6. View Full coverage on Google News

Why Copper May Become Your Favorite Metal

The presidential candidate and Washington governor wants Rapinoe in his administration — should he get elected.

“Clearly my sister’s paycheck is more important than the world her three adopted kids will inherit,” Curtis Ingraham wrote on Twitter.

His department has ignored visas for trafficking victims.

Maybe it was the altitude at Davos.

Apple has released the third beta versions of iOS 13.5, iPadOS 13.5, and MacOS Catalina 10.15.5. Separately, watchOS 6.2.5 beta 3 and tvOS 13.4.5 beta 3 are also available for testing. The third beta versions of iOS 13.5 and iPadOS 13.5 are actually reversioned from iOS 13.4.5 and iPadOS 13.4.5, so if you were testing ... Read More

Apple has released the fourth beta versions of iOS 13.5 and ipadOS 13.5. Additionally, Apple also released the fourth beta builds for watchOS 6.2.5 and tvOS 13.4.5. As of writing, macOS Catalina 10.5.5 beta 4 is not yet available for testing, but presumably will arrive soon as well. iOS 13.5 beta 4 and ipadOS 13.5 ... Read More

strataconf: A detailed agenda for #StrataRx 2013 is now posted: workshops, sessions, speakers + more http://t.co/RtaRpQroaN #healthdata

This is the first time Google says it has provided this kind of data to the public.

Please visit Search Engine Land for the full article.

The following article, BREAKING: New Docs Prove Obama Knew Details Of Flynn Wiretapping…Newly Surfaced Video Shows Obama Explaining How He Stays Out Of FBI Investigations, was first published on 100PercentFedUp.com.

Barack Obama knew. Documents released yesterday that were used to exonerate President Trump’s new NSA General Flynn, prove that President Barack Obama was aware of the details of Michael Flynn’s intercepted phone calls on December 16 with then-Russian Ambassador Sergey Kislyak. On January 5, 2017, then-Deputy Attorney General, Sally Yates attended an Oval Office meeting […]

Continue reading: BREAKING: New Docs Prove Obama Knew Details Of Flynn Wiretapping…Newly Surfaced Video Shows Obama Explaining How He Stays Out Of FBI Investigations ...

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.

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

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.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.

Roland Bruderer
May 1, 2015; 14:1400-1410
Research

Alexey I. Nesvizhskii
Oct 1, 2005; 4:1419-1440
Tutorial

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

WS Harris
Jun 1, 1989; 30:785-807
Reviews

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

S Eisenberg
Oct 1, 1984; 25:1017-1058
Reviews

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews