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Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpo1 in yeast

Keisuke Mori
Apr 29, 2020; 0:jlr.RA120000803v1-jlr.RA120000803
Research Articles




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Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids

Qiuyi Wang
Apr 1, 2020; 61:570-579
Methods




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Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination

Deanna L. Davis
Apr 1, 2020; 61:505-522
Research Articles




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Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism

Sara Straniero
Apr 1, 2020; 61:480-491
Research Articles




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Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells

Kotaro Hama
Apr 1, 2020; 61:523-536
Patient-Oriented and Epidemiological Research




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Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL.

Naoko Sawada
Apr 14, 2020; 0:jlr.RA119000312v1-jlr.RA119000312
Research Articles




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Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice

Yipeng Sui
May 1, 2020; 61:696-706
Research Articles




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The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice

Minjuan Ma
Mar 30, 2020; 0:jlr.RA120000664v1-jlr.RA120000664
Research Articles




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Slc43a3 is a regulator of free fatty acid flux

Kathrin B. Hasbargen
May 1, 2020; 61:734-745
Research Articles




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Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope

Souad Amiar
Apr 15, 2020; 0:jlr.ILR120000753v1-jlr.ILR120000753
Images in Lipid Research




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GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells

Xia Meng
May 1, 2020; 61:591-591
Images in Lipid Research




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UK Tech Weekly Podcast - Episode Three: The Internet of Sex Robots - Facebook likes, AI and Trump

In this week's UK Tech Weekly Podcast host Matt Egan is joined by PC Advisor staff writer Chris Minasians chats about Facebook's new like buttons, the team has contracted smartphone fever from the Mobile World Conference in Barcelona and finally, acting editor of Macworld UK David Price, discusses Donald Trump boycotting Apple.  


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UK Tech Weekly Podcast - Episode Six: The Internet of Board Games (IoBG) + The Budget & AlphaGo

In this week's UK Tech Weekly Podcast host Matt Egan is joined by first time podder Tamlin Magee (1:50), online editor at ComputerworldUK.com, to discuss the UK tech implications of this year's Budget, including rural broadband and driverless cars. Then Christina Mercer, assistant online editor at Techworld.com, chats AlphaGo (10:00) and board games following the AI's historic win over world Go champion Lee Sedol. Later, resident Virtual Reality (VR) enthusiast and PCAdvisor.co.uk staff writer Lewis Painter discussed "the big three" VR headset release dates, pricing and features from HTC, Sony Playstation and Oculus Rift (19:00). Finally, UKTW Podcast regular David Price, acting editor at Macworld.co.uk chats about Apple's big upcoming event (28:45).  


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Episode 12 - The Internet of Voodoo Streaming Services (IoVSS) Apple & Facebook results, Nintendo NX

This week host Matt Egan is joined by regular podder David Price, acting editor of Macworld.co.uk, to discuss Apple's not so awesome results and stalling iPhone sales. Then online editor Scott Carey jumps in to discuss Facebook's far better results and how it has come to dominate the mobile advertising market (15:00) Finally, producer Chris comes out from behind the glass to discuss Nintendo's secretive NX console and having to wait for the new Zelda game (28:00).  


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Episode 19 - The Internet of Xbox 'Hank' Scorpio (IoXHS) LinkedIn, Xbox vs Playstation & WWDC news

Host Matt Egan is joined by Online Editor at Techworld.com Scott Carey to break down Microsoft's mega acquisition of LinkedIn. Staff Writer at PC Advisor Chris joins in to discuss all of the news coming out of E3 and how Xbox and Playstation are set to battle it out again this summer, or will Nintendo and Zelda steal the show? (13:00). Finally, David Price comes on to talk about all of the news coming out of Apple's WWDC developer conference this week, from Hair Force One to watchOS, tvOS, macOS and iOS (26:30) And please do share, rate and review the UK Tech Weekly Podcast.  


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Episode 23 - The Internet of Top Tech Topics (IoTTT) Brexit, Pokemon Go & Tesla

For the second week running hosting duties are taken by Henry Burrell, who is joined by Techworld.com editor Charlotte Jee to discuss the impact of Brexit on the UK's startups. Producer Chris then jumps in to discuss the Pokemon Go launch in the UK and a debate breaks out over whether it is for adults (13:00) Finally, online editor at Computerworld UK Scott Carey brings the latest news around driverless cars, from Tesla's recent struggles and how it may affect the industry in general (25:00)  


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Episode 26 - The Internet of Small Hands Big Phones (IoSHBP) Galaxy Note7, GDS & Instagram stories

Matt Egan is back in the hosting chair to chat with producer Chris about the Samsung Galaxy Note 7 and how we feel about phablets. Techworld.com editor Charlotte Jee comes in to explain what is going on at the GDS (government digital service) and why we should care (13:00). Then online editor at Techworld.com Scott Carey chats Instagram stories, why it is a blatant rip off of Snapchat stories and how the social media giant can get away with being so brazen (22:00).  


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Episode 30 - The Internet of Unlimited Play-Doh (IoUPD): Amazon Dash, Apple tax and headphone sexism

This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  


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Episode 49 - The Internet of Beans and Dickens (IoBaD) Samsung Galaxy S8, billionaire bunkers and Resident Evil 7

Matt Egan hosts as we delve into the tech headlines of the week. Senior Staff Writer at PC Advisor Henry Burrell talks the gang through the latest on Samsung's upcoming smartphone and why it's been delayed, plus another brand comes back from the brink. Online Editor at Techworld Tamlin Magee then explores the strange but true story of Silicon Valley billionaires buying private islands with underground bunkers in case everything really does go Pete Tong. Finally Staff Writer at Macworld UK and PC Advisor Dominic Preston talks us through the frights of the latest Resident Evil game while everyone agrees they can be more terrifying than most horror films.  


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Episode 52 - The Internet of Nostalgia (IoN) Nokia 3310, drone taxis and Apple on the telly

Matt Egan takes us where no other pod has dared gone before (September 2000) and asks Digital Arts Editor Neil Bennett if anyone cares that Nokia is rereleasing the famous 3310. Is it cool to rock one now? Then Techworld Audience Development Editor Christina Mercer lets us know that the future is already here with self driving drone taxis. Would you hitch a lift round Dubai on a massive quadcopter? Finally Deputy Editor at Macworld David Price ruminates on Apple's forecast foray into the world of snackable media content - will it challenge Netflix or try to buy it?  


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Episode 63 - The Internet of the French (IotF) New Surface Pro and Netflix vs Cannes

This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert!  


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Episode 67 - The Internet of Netflix and chill (IoNaC) 100m subs, phone news and Google Glass returns

A classic edition of the pod as we hark back to the hallowed three topic format. Henry Burrell hosts David Price, Scott Carey and Chris Martin to ask just how Netflix got so popular. Will it sustain it though? Windows Phone is also pretty much actually dead but the funeral march is long. Other phone stuff includes the hallowed iPhone 8, the demise of Vertu and Nokia not really being Nokia. David then tells us why Google Glass is back, what it means for the enterprise, and why didn't they realise the first time round that it wasn't a consumer play?  


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Episode 69 - The Internet of internal memos (IoIM) Google sexism row and iPhone 8 leaks

Join Miriam Harris, David Price and Henry Burrell as they dissect the weird internal memo row at Google. Was a male engineer genuinely trying to help Google and make a point about the company being too Left, or is he just an arsehole? Then we describe the iPhone 8 dummy we received this week (take a look at it here: https://www.youtube.com/watch?v=PRNIwh61j_E ) and the revelations that came from the Homepod firmware leak. We also debate the usefulness of an LTE Apple Watch and try to make puns work. Magic.  


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Episode 71: The Internet of iPhone X (IoiX) Plus Apple Watch 3 and Apple TV announcements

This week it is all about Apple as the company announces its eagerly awaited iPhone X and iPhone 8/8 Plus smartphones, a new Apple watch (yawn) and Apple TV news. Macworld UK editor Karen Haslam is our host this week, as she chats to a distinctly unconvinced Dominic Preston about the latest iPhone, followed by David Price on the Apple Watch Series 3, which he likes but not as much as its predecessor. Then everyone piles in together to discuss the quite-good iPhone 8, the quite-late Apple TV 4K, and all the rest of the evening's festivities.  


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Episode 72 - The Internet of Pixels (IoP) Google and Amazon events, Uber and the SNES Mini

We back. Google and Amazon introduced a raft of new products for us to drool over and, of course, apply a degree of scepticism. Jim Martin was on the ground to use all the new Google stuff and has the latest. Scott then talks us through Uber's mishaps, this time its London licence has been revoked. Will the company go public when it wants to? Finally we discuss the SNES Mini which we managed to get our hands on and why Nintendo has such low stock of all its great products.  


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Episode 74 - The Internet of KRACK (IoK) Wi-Fi flaws, Pixel 2 and Facebook vs cyberbullying

David Price is back to host this week, with Christina Mercer breaking down what all the fuss about KRACK is and why you should take precautions with your Wi-Fi. Henry Burrell reviewed the Google Pixel 2 this week so gives us his thoughts on the device. You might want to avoid the larger XL though. We then discuss Facebook's idea to counterattack cyberbullying. Charlotte Jee recently spoke with the company to see what they are doing, but will it work?  


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Episode 75 - The Internet of Driverless Pods (IoDP) Hands on with the iPhone X, FairPhone and Driverless Car design

After a lengthy hiatus we are back to FINALLY talk about the iPhone X. Computerworld UK editor Scott Carey is in the hosting chair to chat with Chris Martin, reviews editor at Tech Advisor and Macworld UK, now that we have got our hands on one. Chris talks us through what he likes and dislikes so far about the pricey smartphone.


Then Miriam Harris, staff writer at Digital Arts jumps in to discuss the design principles behind driverless cars and what we can expect in the future (17:00).


Finally, pod debutante Caroline Vanier, senior staff writer at Tech Advisor France talks about the FairPhone and if it is a new model for the smart phone industry (28:00).

 

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Episode 76 - The Internet of Deals (IoD) Black Friday, Mac root bug, Pixel Buds and Animal Crossing

It's a bumper pod! David Price leads Ashleigh Macro and Henry Burrell down the topical rabbit hole to discuss why Black Friday largely sucks, but is an interesting venture for publishers as well as consumers. Who else bought a Switch?


We then tackle the Mac root issue that hit headlines worldwide before tearing the Pixel Buds a new one. And we all downloaded Animal Crossing: Pocket Camp to see what the fuss is about.

 

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Episode 78 - The Internet of the pod before Christmas (IotPBC) iMac Pro, Netflix's Twitter misstep and Apple buys Shazam

Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?


We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?


In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired?

 

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Episode 79 - The Internet of New Year (IoNY) Meltdown & Spectre, iPhone batteries, iMac Pro and the VFX Bafta noms

2018 lands with a distinct thud as Charlotte Jee tackles Meltdown and Spectre, David Price wrestles with Apple's batteries and its new iMac Pro, before Miriam Harris works through the Bafta nominations for visual effects. Henry Burrell leads us down the rabbit hole.

 

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Episode 84 - The Internet of Porn (IoP) Nectome, Galaxy S9 and UK porn age checks

The gang returns with an eclectic mix of tech chat. Can Nectome really download your thoughts - while killing you - to preserve your memories forever in the cloud? We didn't make this up.


Then we discuss the brand new Samsung Galaxy S9, phone cameras and crap AR before discussing how the UK should go about contracting a company to age check porn site users.

 

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Episode 94 - The Internet of Screens (IoS) Netflix is huge and Fortnite is popular

This week it’s David Price in the hosting seat to dig into two meaty tech topics: how does Netflix buy and develop its massive content library, and why is Fortnite such a sensation?


Helping him dig into Netflix is Computerworld UK editor Scott Carey, with our new entertainment and lifestyle editor at Tech Advisor Dominic Preston joining in.


Then staff writer at Tech Advisor Sean Bradley is on hand to talk about how Fortnite has become such a sensation, and if it is built to last.

 

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Episode 95 - The Internet of Digital Ministers (IoDM) Political turmoil, Surface Go and CaveX

Join host Scott Carey as the team dissects Tory meltdown and what it means for tech and the ministers we haven't heard of. What can they actually do to help the country? Charlotte Jee explains.


Then Henry Burrell chats on the new Microsoft Surface Go, an 'affordable' Surface tablet that actually still breaks the bank. Who is it for, and is Microsoft really chasing the iPad market?


David Price rounds up the pod with Musk Corner as everyone's favourite Twitter megalomaniac flies off to Thailand to help with a cave rescue - but should he stay out of it?

 

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Episode 97 - The Internet of Big Companies (IoBC) Apple results, Amazon worker rights and Google Cloud Next

This week our host Scott Carey is joined by Macworld UK editor Karen Khan to chat about Apple's latest blockbuster results.


Then group production editor Tamlin Magee jumps in to discuss Amazon's working practices following the collective action around Prime Day.


Finally, Scott chats through his experience at the Google Cloud Next conference in San Francisco last week to see how it is trying to compete with the big boys at Amazon and Microsoft.

 

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Episode 102 - The Internet of Tennis Max (IoTM) Apple event special, new iPhones and Apple Watch

A quick-fire reaction Apple special, recorded the morning after new iPhones and an Apple Watch were announced at an event in California.


Henry Burrell joins David Price, Ashleigh Macro and Scott Carey to discuss which products we'll be buying, avoiding and coveting over the Christmas period.


Is the new iPhone named terribly? Is it an upgrade at all? What wasn't announced? And does Scott give the new Apple Watch any praise at all? It's all here.

 

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Episode 104 - The Internet of Circles (IoC) RIP Google+, Pixel 3 and new tech in films

This week our host Scott Carey catches up on the Google+ breach news and the final demise of the doomed social media network before being joined by consumer technology editor at Tech Advisor, Henry Burrell, to talk about Google's latest batch of smartphones: the Pixel 3 and Pixel 3 XL.


Then Techworld reporter Tamlin Magee joins to talk about the technology-related films screening during the London Film Festival this month and his hopes for more utopian tech-flecked stories in the future.

 

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Episode 105 - The Internet of Good & Bad (IoG&B) Google Rubin scandal and iPhone XR hands-on

It's episode 105, and David Price takes on hosting duties as the team dissect the best and absolute worst of the week's tech developments.


Scott Carey talks us through the troubling and wide-ranging allegations of sexual misconduct at Google, and discusses how this relates to the tech industry's culture of protected privilege, and to the #metoo movement.


Then Henry Burrell, fresh from a briefing at Apple HQ, reports his distinctly positive first impressions of the iPhone XR, which he would gladly recommend to tech newbie grandmas, and also to Scott.

 

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Episode 111 - The Internet of Not Watching Films (IoNWF) Bird Box, Black Mirror and bent iPads

Happy New Year from the UK Tech Weekly Podcast!


We are back this week to discuss what we have been watching (or not watching) over the festive period, including Scott Carey on the meme-marketed sensation of Bird Box and what this says about Netflix's ability to dominate the cultural conversation. Then Tamlin Magee jumps in to talk about the interactive Black Mirror movie Bandersnatch and why it may have been destined to fail.


Lastly David Price steps out of the hosting chair to talk about bendy iPads and Apple's strange rhetoric.

 

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Episode 112 - The Internet of Controversial Dildos (IoCD) CES roundup ft. sex toys and smart wood

This week our host Scott Carey catches up with Sean Bradley and Dominic Preston fresh off the back of the International Consumer Electronics Show (CES) in Las Vegas.


Dom explains why he was surprised, both in a good and bad way, by the latest foldable screen technology and Sean talks about what is going on in the gaming laptop space, as Alienware looks to soften its image.


Then Dom talks about a piece of connected wood and the gang break down the big controversy from the show floor regarding a certain innovative dildo.


We are also announcing the sad news that the UK Tech Weekly Podcast will be going on an indefinite hiatus while we reassess our podcasting output. We would like to thank anyone that has taken the time to listen to us for these one hundred and twelve (112!) episodes and rest assured we will be back in some guise soon.

 

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WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles]

This manuscript has been withdrawn by the Author.




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WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews]

This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98.




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Fatty acid oxidation and photoreceptor metabolic needs [Thematic Reviews]

Photoreceptors have high energy-demands and a high density of mitochondria that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) of fuel substrates. Although glucose is the major fuel for central nervous system (CNS) brain neurons, in photoreceptors (also CNS), most glucose is not metabolized through OXPHOS but is instead metabolized into lactate by aerobic glycolysis. The major fuel sources for photoreceptor mitochondria remained unclear for almost six decades. Similar to other tissues (like heart and skeletal muscle) with high metabolic rates, photoreceptors were recently found to metabolize fatty acids (palmitate) through OXPHOS. Disruption of lipid entry into photoreceptors leads to extracellular lipid accumulation, suppressed glucose transporter expression, and a duel lipid/glucose fuel shortage. Modulation of lipid metabolism helps restore photoreceptor function. However, further elucidation of the types of lipids used as retinal energy sources, the metabolic interaction with other fuel pathways, as well as the crosstalk among retinal cells to provide energy to photoreceptors is not yet known. In this review, we will focus on the current understanding of photoreceptor energy demand and sources, and potential future investigations of photoreceptor metabolism.




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The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice [Research Articles]

Excessive lipid deposition is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long non-coding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a high-fat diet (HFD) and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator sterol regulatory element–binding transcription factor 1c (SREBP-1c) and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622–miR-742-3p–SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD.




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Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL. [Research Articles]

Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.




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Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope [Images in Lipid Research]




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Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpo1 in yeast [Research Articles]

The yeast protein Mpo1 belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpo1 is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpo1, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpo1 family are especially important for Mpo1 activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH long-chain FAs, Mpo1 also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingolipids. These results indicate that Mpo1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth of mpo1 cells is delayed upon carbon deprivation, suggesting that the Mpo1-mediated conversion of 2-OH FAs to non-hydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as-yet-unknown functions and activities of other Mpo1 family members.




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Predictions and Policymaking: Complex Modelling Beyond COVID-19

1 April 2020

Yasmin Afina

Research Assistant, International Security Programme

Calum Inverarity

Research Analyst and Coordinator, International Security Programme
The COVID-19 pandemic has highlighted the potential of complex systems modelling for policymaking but it is crucial to also understand its limitations.

GettyImages-1208425931.jpg

A member of the media wearing a protective face mask works in Downing Street where Britain's Prime Minister Boris Johnson is self-isolating in central London, 27 March 2020. Photo by TOLGA AKMEN/AFP via Getty Images.

Complex systems models have played a significant role in informing and shaping the public health measures adopted by governments in the context of the COVID-19 pandemic. For instance, modelling carried out by a team at Imperial College London is widely reported to have driven the approach in the UK from a strategy of mitigation to one of suppression.

Complex systems modelling will increasingly feed into policymaking by predicting a range of potential correlations, results and outcomes based on a set of parameters, assumptions, data and pre-defined interactions. It is already instrumental in developing risk mitigation and resilience measures to address and prepare for existential crises such as pandemics, prospects of a nuclear war, as well as climate change.

The human factor

In the end, model-driven approaches must stand up to the test of real-life data. Modelling for policymaking must take into account a number of caveats and limitations. Models are developed to help answer specific questions, and their predictions will depend on the hypotheses and definitions set by the modellers, which are subject to their individual and collective biases and assumptions. For instance, the models developed by Imperial College came with the caveated assumption that a policy of social distancing for people over 70 will have a 75 per cent compliance rate. This assumption is based on the modellers’ own perceptions of demographics and society, and may not reflect all societal factors that could impact this compliance rate in real life, such as gender, age, ethnicity, genetic diversity, economic stability, as well as access to food, supplies and healthcare. This is why modelling benefits from a cognitively diverse team who bring a wide range of knowledge and understanding to the early creation of a model.

The potential of artificial intelligence

Machine learning, or artificial intelligence (AI), has the potential to advance the capacity and accuracy of modelling techniques by identifying new patterns and interactions, and overcoming some of the limitations resulting from human assumptions and bias. Yet, increasing reliance on these techniques raises the issue of explainability. Policymakers need to be fully aware and understand the model, assumptions and input data behind any predictions and must be able to communicate this aspect of modelling in order to uphold democratic accountability and transparency in public decision-making.

In addition, models using machine learning techniques require extensive amounts of data, which must also be of high quality and as free from bias as possible to ensure accuracy and address the issues at stake. Although technology may be used in the process (i.e. automated extraction and processing of information with big data), data is ultimately created, collected, aggregated and analysed by and for human users. Datasets will reflect the individual and collective biases and assumptions of those creating, collecting, processing and analysing this data. Algorithmic bias is inevitable, and it is essential that policy- and decision-makers are fully aware of how reliable the systems are, as well as their potential social implications.

The age of distrust

Increasing use of emerging technologies for data- and evidence-based policymaking is taking place, paradoxically, in an era of growing mistrust towards expertise and experts, as infamously surmised by Michael Gove. Policymakers and subject-matter experts have faced increased public scrutiny of their findings and the resultant policies that they have been used to justify.

This distrust and scepticism within public discourse has only been fuelled by an ever-increasing availability of diffuse sources of information, not all of which are verifiable and robust. This has caused tension between experts, policymakers and public, which has led to conflicts and uncertainty over what data and predictions can be trusted, and to what degree. This dynamic is exacerbated when considering that certain individuals may purposefully misappropriate, or simply misinterpret, data to support their argument or policies. Politicians are presently considered the least trusted professionals by the UK public, highlighting the importance of better and more effective communication between the scientific community, policymakers and the populations affected by policy decisions.

Acknowledging limitations

While measures can and should be built in to improve the transparency and robustness of scientific models in order to counteract these common criticisms, it is important to acknowledge that there are limitations to the steps that can be taken. This is particularly the case when dealing with predictions of future events, which inherently involve degrees of uncertainty that cannot be fully accounted for by human or machine. As a result, if not carefully considered and communicated, the increased use of complex modelling in policymaking holds the potential to undermine and obfuscate the policymaking process, which may contribute towards significant mistakes being made, increased uncertainty, lack of trust in the models and in the political process and further disaffection of citizens.

The potential contribution of complexity modelling to the work of policymakers is undeniable. However, it is imperative to appreciate the inner workings and limitations of these models, such as the biases that underpin their functioning and the uncertainties that they will not be fully capable of accounting for, in spite of their immense power. They must be tested against the data, again and again, as new information becomes available or there is a risk of scientific models becoming embroiled in partisan politicization and potentially weaponized for political purposes. It is therefore important not to consider these models as oracles, but instead as one of many contributions to the process of policymaking.




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WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other]

Withdrawn by Author.




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Multiple hypothesis testing in proteomics: A strategy for experimental work [Invited]

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.




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Oxidative stress-mediated regulation of proteasome complexes [Other]

Oxidative stress has been implicated in aging and many human diseases, notably neurodegenerative disorders and various cancers. The reactive oxygen species that are generated by aerobic metabolism and environmental stressors can chemically modify proteins and alter their biological functions. Cells possess protein repair pathways to rescue oxidized proteins and restore their functions. If these repair processes fail, oxidized proteins may become cytotoxic. Cell homeostasis and viability are therefore dependent on the removal of oxidatively damaged proteins. Numerous studies have demonstrated that the proteasome plays a pivotal role in the selective recognition and degradation of oxidized proteins. Despite extensive research, oxidative stress-triggered regulation of proteasome complexes remains poorly defined. Better understanding of molecular mechanisms underlying proteasome function in response to oxidative stress will provide a basis for developing new strategies aimed at improving cell viability and recovery as well as attenuating oxidation-induced cytotoxicity associated with aging and disease. Here we highlight recent advances in the understanding of proteasome structure and function during oxidative stress and describe how cells cope with oxidative stress through proteasome-dependent degradation pathways.