gg Unplugging With SmallBox Web Design By linkworxseo.wordpress.com Published On :: Sun, 02 Dec 2012 15:52:00 +0000 How did you feel? Well, considering I spent almost no time doing anything but working on the business, this is sorta a tough one to answer. Most of the time when I want to unplug I may disappear for an entire weekend to get away from the daily work habits that flow over into the […] Full Article BLOGGING WEB CONTENT indiana indianapolis races redbull smallbox super-sport-bike thinkhit
gg 17 Memes About Catching The Red Dot That Will Have You Giggling All Day By cheezburger.com Published On :: Wed, 14 Aug 2019 12:44:00 -0700 It's every cat's greatest dream to finally catch that red dot. And sometimes they do (meaning we get tired of holding down the laser and pointing). Full Article funny cat memes lolcats funny memes Memes lol funny cats funny cat memes
gg Now try hugging me and see what happens ! By cheezburger.com Published On :: Mon, 11 Nov 2024 10:00:00 -0800 Full Article
gg NAACP’s Attorney Griggs: It’s Time to Make Sure the Will of the People is Heard By www.gregpalast.com Published On :: Thu, 31 Oct 2024 18:03:35 +0000 During Tuesday night’s Save Your Vote Special Broadcast Event, attorney Gerald Griggs, who serves as the President of the NAACP of Georgia, called for action to counter the increasing threats to voters of color from white supremacist groups. It’s a threat that the Palast Investigations team knows is... READ MORE Full Article Articles Vigilante
gg Newegg Fantastech Sale - $100 PlayStation GC $90, $100 Xbox GC $88, $50 Nintendo GC $45 and More By www.cheapassgamer.com Published On :: Mon, 09 Oct 2023 20:32:59 +0000 PlayStation $100 GC $90 w/coupon: FTTCX9645 Xbox $100 GC $88 w/coupon: FTTCX9426 Nintendo $50 GC $45 w/coupong: FTTCX9425 Sonic MotherBoard $189.99 All Gaming items at Fantastech Sale Everything at NewEgg's Fantastech Sale Full Article
gg Refurbished iPads (and more Apple Refurbs) on Sale at Newegg By www.cheapassgamer.com Published On :: Mon, 09 Oct 2023 20:45:21 +0000 Top 3 Most Popular 1. Refurbished: Apple iPad Air 2 A1567 (WiFi + Cellular Unlocked) 64GB Silver Bundle $159.99 w/ Case, Bluetooth Earbuds, Tempered Glass, Stylus, Charger Limited time offer, ends 10/30 2. Refurbished: Apple iPad Pro 11 3rd Gen (2021) Wi-Fi Only 8GB/128GB - Space Gray $639 3. Refurbished: Apple iPad 7 (2019) Wi-Fi Only 3GB/32GB - Space Gray $189 All Apple Refurbished at Newegg Full Article
gg Our Favorite Outdoor Furniture Brand Is Having Its Biggest Sale of the Year By www.apartmenttherapy.com Published On :: Tue, 12 Nov 2024 17:45:00 -0500 If you're looking to save big on your next outdoor furniture splurge, now's the ultimate time. READ MORE... Full Article Life Black Friday Cyber Monday 2024 Design entertaining furniture shopping Outdoor Furniture Outdoors Outer Sales & Events Shopping Slideshow
gg Violent and aggressive children. Caring for those who care By lx.iriss.org.uk Published On :: Wednesday, August 12, 2015 - 12:44 The topic of domestic violence is an emotive one conjuring visions of child abuse by parents or carers, or marital violence, in general abuse by men of their wives or partners. According to published police statistics in Scotland for the years of 2012 – 13 male violence of women accounted for 80% of all domestic abuse, and in 2014 over 2,600 children in Scotland were identified as needing protection from abuse. This is particularly concerning since the NSPCC suggests that, for every child who has been identified, there are 8 other children who are at risk but who are ‘under the radar’. These statistics, highlighting the underlying nature of inter-family abuse relationships, i.e. the abuse of less powerful and more vulnerable family members by more powerful adults, undoubtedly account for the majority of the abuse situations within family homes. However this is, sadly, not the whole story. Understanding abuse within a family means recognising the impact of sibling aggression on every family member. It also needs to encompass the growing recognition of child to parent aggression and it is this latter aspect of inter-family relationships with which this article is primarily concerned. Full Article
gg Alex Jones: Infowars Tagged For Death By crooksandliars.com Published On :: Tue, 12 Nov 2024 16:48:10 +0000 One of the oldest conspiracy and 'black helicopter' frauds is now facing the hand of the law. Alex Jones is reaping what he sowed. During a portion of his Info Wars program, Alex Jones lamented over how his show is being stripped and sold off after a just verdict against him for his lies about Sandy Hook victims and their families. A verdict he described as a "Nazi show trial." Sucks to be you, Alex. And it couldn't happen to a more deserving guy. JONES: InfoWars, the equipment, InfoWars.com, InfoWarsStore.com, and a whole bunch of other stuff is at a federal bankruptcy auction from the fake judgments and the rigged trials where I was found guilty beforehand and they had literal show trials out of the Soviet Union or Nazi Germany. Robin, I walked in here during the break after getting a glass of water, saw the auctioneers inside the building, going around surveying from the last time they were here to make sure all the stuff's here. Everything tagged, everything marked, this death. Good riddance, you motherfrakker. Rudy Giuliani is trying to avoid the same fate. We need more of these creeps to face the same punishment. read more Full Article Alex Jones bankruptcy InfoWars
gg Greek Style Beef and Eggplant Rice (aka Moussaka Rice) By www.closetcooking.com Published On :: Mon, 04 Nov 2024 10:00:58 +0000 A one-pan Greek style rice with beef and eggplant in a tasty tomato sauce! Moussaka is a Greek dish typically containing layers of eggplant, a meat sauce, and a bechamel sauce and it takes a bit of time to make it. This dish is inspired by the flavours of moussaka as a quick and easy... Read On → The post Greek Style Beef and Eggplant Rice (aka Moussaka Rice) appeared first on Closet Cooking. Full Article Beef Food Gluten-free Greek Lamb Main Course Meal Prep Mediterranean One-Pan One-Pot Recipe Rice
gg Doggone This Client! By clientsfromhell.tumblr.com Published On :: Sun, 09 Jan 2022 06:00:23 -0800 I’m at a briefing with a client, along with a board made up of the client’s in-house developers and designers. While discussing an idea with some of the other people in the room, the client stands up and starts hitting the desk with the newspaper. Me: “Excuse me, but what are you doing?” Client: “Hush, this works on my dogs at home. It should work on you too.” He beats the table with the newspaper for a few seconds. Client: “Now, sit, and stay.” He continues to beat the table. Me: “I’m sorry, this is ridiculous. I’m terminating you as a client.” As I walked towards the door, the client jumped up from their seat and blocked the door. Client: “If you want a snack, I’ve got some under my desk, no need to leave the meeting!” At this point, I shoved him aside, and walked out, followed by him. Whistling, and shouting “come!” Full Article
gg These countries are facing the biggest health impacts By inhabitat.com Published On :: Mon, 03 Jul 2023 15:30:00 +0000 Medical Aid, a South African insurance comparison website, investigated the effects of environmental issues like poor water quality, pollution, sanitation and chemical exposure on the health of citizens in 103 countries around the world. The information is summarized in a report titled, "Climate Health: Where in the World is Climate Change Impacting Health the Most?"[...] Full Article Environment Climate Change Health world health Health Climate Change
gg Might We Suggest the Melons? By cheezburger.com Published On :: Wed, 16 Apr 2014 16:00:00 -0700 Full Article lady bits las vegas sexy times
gg Pando, the world's largest organism, may have been growing nonstop since the 1st humans left Africa, study suggests By www.livescience.com Published On :: Tue, 12 Nov 2024 17:17:38 +0000 The clonal quaking aspen known as Pando is between 16,000 and 80,000 years old. Full Article Plants Planet Earth
gg Famous Paintings Get “Hedgehogged” by a Russian Artist By englishrussia.com Published On :: Wed, 06 Apr 2022 14:54:56 +0000 The post Famous Paintings Get “Hedgehogged” by a Russian Artist appeared first on English Russia. Full Article Culture Funny art funny
gg Jo Dunkley, Suzanne Staggs and colleagues awarded $53M to upgrade prominent observatory By www.princeton.edu Published On :: Thu, 18 May 2023 14:55:02 -0400 The National Science Foundation has awarded a $52.66 million grant to fund a major infrastructure upgrade to the Simons Observatory in the Atacama Desert of Chile. Upgrades are expected to take about five years; the resulting facility will be known as the Advanced Simons Observatory (ASO). Full Article
gg 2025 Oscar Contenders: ‘Quota’ Directors Job Roggeveen, Joris Oprins, and Marieke Blaauw By www.cartoonbrew.com Published On :: Fri, 01 Nov 2024 02:55:25 +0000 The Oscar-nominated trio behind 'A Single Life' is back with a new dark comedy about climate change and individual responsibility. Full Article Awards Shorts Joris Oprins Marieke Blaauw Oscars 2025 Shorts Roggeveen
gg Is Blogging Still Important For Life And Business? By www.rssground.com Published On :: Thu, 31 Jan 2019 00:35:06 +0000 RSS Ground is preparing a major update for its blog posters. And we would like to share some thoughts on blogging and its place in today’s life. Just recently “blogging” was extremely popular. Personal and business blogs are a part of our everyday’s life that we can hardly remember the times when it was otherwise. […] The post Is Blogging Still Important For Life And Business? appeared first on RSSground.com. Full Article eBusiness Tips blog posting automation blogging business blogging make money with blog
gg Meet New Automated WordPress and Blogger Posters By www.rssground.com Published On :: Wed, 20 Feb 2019 11:08:57 +0000 We have finally completed the renovation of our tools interfaces. Improved and unified layouts across all of our content generators and posters. And today it’s time to introduce updated WordPress and Blogger posters. These brand new content sharing tools will make a process of automated blog posting work like a charm. WordPress Poster User Guide […] The post Meet New Automated WordPress and Blogger Posters appeared first on RSSground.com. Full Article RSS Ground News automated posting Blogger poster blogging Wordpress poster
gg Personal feeds as new triggers in Zapier, IFTTT & Pabbly Connect By www.rssground.com Published On :: Tue, 07 May 2024 16:31:14 +0000 We’ve recently tapped into the power of automation with our integrations with IFTTT, Zapier, and Pabbly Connect! Now, you can effortlessly manage your content across the web, extending your reach and impact through automated posting campaigns! Learn more about RSS Ground integration with major automation platforms But hold onto your hats, because we’re just getting […] The post Personal feeds as new triggers in Zapier, IFTTT & Pabbly Connect appeared first on RSSground.com. Full Article RSS Ground News change log service updates
gg Blogger Poster custom apps for volume posting By www.rssground.com Published On :: Wed, 09 Oct 2024 16:02:59 +0000 Lately, we’ve noticed an increased number of reports indicating issues with Blogger posting campaigns, where the error message “(403) We’re sorry, but one or more limits for the requested action have been exceeded” is displayed. To make it easier for you, in Blogger Poster we use our own Google Cloud app to make posts to […] The post Blogger Poster custom apps for volume posting appeared first on RSSground.com. Full Article RSS Ground News
gg The perfect ski holiday in Méribel, the beating heart of France’s biggest ski area By www.telegraph.co.uk Published On :: Wed, 30 Oct 2024 13:00:00 GMT Full Article structure:travel/ski structure:travel structure:travel/ski/resort-guides storytype:standard structure:eg-general structure:us-content structure:better-life/better-life-evergreen structure:better-life/better-life-guide structure:travel/destination-guides-100 topics:places/europe topics:places/france
gg NBA Hall of Famer Reggie Miller Is Breaking the Cycling Mold By www.pinkbike.com Published On :: Sat, 9 Nov 2024 00:00:00 PST “Me being 6 feet 7 inches, I’m not your normal height-weight type cyclist. But that motivates me to get better, to be better, to go against these guys.” Full Article
gg In this school’s election, it’s pizza vs. chicken nuggets, with democracy as the winner By www.npr.org Published On :: Thu, 31 Oct 2024 05:00:00 -0400 At an Arizona tribal school, it's a fierce campaign to pick the top school lunch, as students learn about making their voice count Full Article
gg 'A Real Pain' film presents the parallels of generational struggle By www.jpost.com Published On :: Wed, 30 Oct 2024 15:50:06 GMT From the horror of the Holocaust to the struggles that the cousins face in the modern day, the movie is about the overall pains of life, film star Jennifer Grey iterated. Full Article Holocaust film world war ii trauma Jesse Eisenberg
gg Biden’s Signature Climate ‘Boondoggle’ Might Be On Chopping Block After Trump Win By libertyunyielding.com Published On :: Sun, 10 Nov 2024 21:09:43 +0000 By David Blackmon In the wake of the election of President Donald Trump to serve a second term in office, along with presumptive Republican majorities in both houses of Congress, many are now asking about what the future will hold for the oddly named Inflation Reduction Act. Trump made it repeatedly clear on the campaign […] The post Biden’s Signature Climate ‘Boondoggle’ Might Be On Chopping Block After Trump Win appeared first on Liberty Unyielding. Full Article Business Law and Government
gg Why did Hamilton struggle when Russell was competitive? By www.bbc.com Published On :: Tue, 05 Nov 2024 07:52:47 GMT BBC F1 correspondent Andrew Benson answers your questions following the Sao Paulo Grand Prix. Full Article
gg Mings penalty mistake biggest I've ever witnessed - Emery By www.bbc.com Published On :: Wed, 06 Nov 2024 21:13:23 GMT Tyrone Mings became the first Englishman to concede a penalty on his Champions League debut in bizarre fashion as Aston Villa lost to Brugge. Full Article
gg iPhone SE 4 expected to launch in March 2025, supply chain data suggests - Business Standard By news.google.com Published On :: Wed, 13 Nov 2024 05:59:10 GMT iPhone SE 4 expected to launch in March 2025, supply chain data suggests Business StandardiPhone SE4 is likely to launch soon and here are 5 big upgrades we are expecting India TodayApple iPhone SE 4 to launch next year, likely to become the cheapest iPhone to support Apple Intelligence... MoneycontroliPhone SE 4 may spell trouble for iPhone 16 and premium Android phones, here’s why Hindustan TimesiPhone SE 4 Camera Production to Begin Soon Ahead of Anticipated Debut in March 2025: Report Gadgets 360 Full Article
gg The biggest risk to stocks after Trump's victory is China's reaction to a trade war, research firm says By markets.businessinsider.com Published On :: Tue, 12 Nov 2024 19:53:19 +0000 If Trump's proposed 60% tariff against China is enacted and the country responds aggressively, it could pressure some of America's largest companies. Full Article Markets mi-exclusive stock-market-outlook china-tariffs trade-war sp-500 donald-trump
gg The full list of major US companies slashing staff this year, including Goldman Sachs, Meta, and Chegg By www.businessinsider.com Published On :: Wed, 13 Nov 2024 01:37:31 +0000 Companies have continued to cut jobs in 2024 after a wave of layoffs last year. Meta, Goldman Sachs, Google, and Tesla are among those shedding staff. Full Article Careers Tech Retail Finance nike intel citi layoffs ai corporate-restructuring blackrock rent-the-runway unity twitch duolingo amazon-prime-video amazon-mgm-studios amazon discord google flexport irobot ups tesla apple gta-vi xbox indeed lucid-motors dell paramount cisco goldman-sachs tiktok meta bed-bath-beyond visa nissan
gg Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet By clashdaily.com Published On :: Tue, 05 Nov 2024 10:23:15 +0000 There is a reason Joe Rogan became the world's largest podcaster. He doesn't take his audience -- or his guests -- for granted. He wants MEANINGFUL conversations. The post Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet appeared first on Clash Daily. Full Article News Clash
gg The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think By clashdaily.com Published On :: Tue, 05 Nov 2024 11:18:25 +0000 There's a reason Hitler holds a special place of disgrace in public memory. He combined the ambition and destruction of Attila The Hun with the personal malice of a serial killer. The post The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think appeared first on Clash Daily. Full Article Videos
gg Kamala's Campaign Is Still Aggressively Shaking Down Supporters For Cash By www.westernjournal.com Published On :: Tue, 12 Nov 2024 11:00:27 +0000 Even after her loss on Nov. 5, Vice President Kamala Harris’ election campaign is still hounding donors for money. Harris’ campaign has bombarded supporters with fundraising messages following her election […] The post Kamala's Campaign Is Still Aggressively Shaking Down Supporters For Cash appeared first on The Western Journal. Full Article News 2024 election Democratic National Committee Democratic Party Democrats Kamala Harris U.S. News WJ Wire
gg Insult to Injury: MSNBC and CNN Suffer Staggering Ratings Plunge Following Trump Victory By www.westernjournal.com Published On :: Tue, 12 Nov 2024 14:25:40 +0000 Left-wing networks had plenty of bad news for their viewers as former President Donald Trump stormed to victory in the Nov. 5 election. Now, they’re getting plenty of bad news […] The post Insult to Injury: MSNBC and CNN Suffer Staggering Ratings Plunge Following Trump Victory appeared first on The Western Journal. Full Article News 2024 election CNN Donald Trump Fox & Friends Liberal media Media watch MSNBC Politics U.S. News
gg A novel method produces native light-harvesting complex II aggregates from the photosynthetic membrane revealing their role in nonphotochemical quenching [Bioenergetics] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ. Full Article
gg India Budget 2018: Who are the Biggest Winners and Losers? By www.chathamhouse.org Published On :: Fri, 02 Feb 2018 12:13:14 +0000 India Budget 2018: Who are the Biggest Winners and Losers? Expert comment sysadmin 2 February 2018 Any claims to boost farmers’ prospects will inevitably be seen as political, coming ahead of a series of key elections. But this budget recognises India’s most pressing concerns - and seeks to address them. — Hundreds of farmers sit in pits as a protest against government plans for land acquisition in October 2017. Photo By Vishal Bhatnagar/NurPhoto via Getty Images. In 2016 India’s prime minister, Narendra Modi, pledged to double farmers’ incomes by 2022. While the pledge may have been aspirational, reliant on good weather as much as government policy, the 2018/19 budget demonstrates the depth of the government’s commitment to the agriculture sector. There’s clearly a political edge to any moves to bolster agriculture: any solace to rural India will be described as political opportunism until most people in India are not engaged directly or indirectly in the agricultural sector. And with a number of state elections coming up this year and a general election next – suggestions that it will be brought forward have increased in volume since the budget – a politically-astute budget is unsurprising. At the same time, there is a real sense of crisis in Indian agriculture which the budget is attempting to ameliorate. Significant hike in infrastructure spending The budget – which has Keynesian undertones – announces both direct and indirect support for rural India; it increases significantly the price at which the government purchases agricultural produce, and offers a range of further support through initiatives in areas such as irrigation. Furthermore, there is a significant hike in spending on infrastructure – roads, railways, ports and waterways – with a major allocation for rural infrastructure. While government spending on infrastructure had been growing, the 2018/19 budget appears to accept that innovative funding models to fund rural projects are unlikely to work – instead, rural highways will have to be funded from overall taxation, as is generally the norm. The other bold initiative focuses on healthcare. One hundred million poor families (so around half a billion Indians in total) will receive up to Rs500,000 for medical care under a health insurance programme. Given the correlation between ill health and poverty, this should have implications for the economy as well as healthcare itself. At the moment poverty effectively excludes many Indians from private healthcare. Education too received a boost, with several proposals including teacher training. There have long been concerns over the quality of Indian education. In particular, even where schools exist physically, teachers themselves are absent. As is often the case with India, the question will be in the implementation. While there are bound to be hiccups, the current Indian government does appear to realise the need for on-the-ground, visible change. The recent state election in Gujarat demonstrated that while the ruling Bharatiya Janata Party (BJP) is clearly favourite to win another term, it is not invulnerable. If the changes do not reach the “last mile”, then they will accrue neither the economic nor the political benefits. The downsides? Increased taxes will raise inflation, potentially exacerbated by sustained government borrowing; a 20% rise in customs duty will affect imports of mobile phones (though benefit domestic producers and encourage other foreign firms to set up manufacturing plants in India) and some of the revenue projections appear optimistic. On balance though, this is a budget that recognises the most pressing challenges which India faces, and attempts to provide solutions to them. This article was originally published in The Independent. Full Article
gg Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents By www.mcponline.org Published On :: 2004-12-01 Philip L. RossDec 1, 2004; 3:1154-1169Research Full Article
gg Iraq’s Future: Elections, Corruption and the Struggle for a State By f1.media.brightcove.com Published On :: Wed, 30 May 2018 00:00:00 +0100 Full Article
gg Shared requirements for key residues in the antibiotic resistance enzymes ErmC and ErmE suggest a common mode of RNA recognition [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex. Full Article
gg Can a chemotaxis-consumption system recover from a measure-type aggregation state in arbitrary dimension? By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST Frederic Heihoff Proc. Amer. Math. Soc. 152 (), 5229-5247. Abstract, references and article information Full Article
gg The Nightly Habit Cardiologists Are Begging You to Never, Ever Do By www.yahoo.com Published On :: 2024-11-11T15:25:00Z Full Article
gg Vybz Kartel, Shenseea nominated for Best Reggae Album Grammy By jamaica-star.com Published On :: Fri, 08 Nov 2024 12:04:07 -0500 Full Article
gg DJ Specs gives up university to juggle music By jamaica-star.com Published On :: Mon, 11 Nov 2024 05:01:06 -0500 In 2020, when Anthony Parker, known to his fans as DJ Specs, decided to trade his textbooks for turntables, he didn't just pivot his career -- he pivoted his entire life. At just 25 years old, this Kingston-born DJ has already carved out a space... Full Article
gg N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis. GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage. Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS. Full Article
gg Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria. Full Article
gg Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Cα, 13Cβ, 1Hα, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca2+, but do bind Zn2+, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested. Full Article
gg A Novel Mechanism for NF-{kappa}B-activation via I{kappa}B-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation By www.mcponline.org Published On :: 2020-12-01 Yi LiuDec 1, 2020; 19:1968-1985Research Full Article
gg Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells [Signal Transduction] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function. Full Article
gg AggreCount: an unbiased image analysis tool for identifying and quantifying cellular aggregates in a spatially defined manner [Methods and Resources] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Protein quality control is maintained by a number of integrated cellular pathways that monitor the folding and functionality of the cellular proteome. Defects in these pathways lead to the accumulation of misfolded or faulty proteins that may become insoluble and aggregate over time. Protein aggregates significantly contribute to the development of a number of human diseases such as amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease. In vitro, imaging-based, cellular studies have defined key biomolecular components that recognize and clear aggregates; however, no unifying method is available to quantify cellular aggregates, limiting our ability to reproducibly and accurately quantify these structures. Here we describe an ImageJ macro called AggreCount to identify and measure protein aggregates in cells. AggreCount is designed to be intuitive, easy to use, and customizable for different types of aggregates observed in cells. Minimal experience in coding is required to utilize the script. Based on a user-defined image, AggreCount will report a number of metrics: (i) total number of cellular aggregates, (ii) percentage of cells with aggregates, (iii) aggregates per cell, (iv) area of aggregates, and (v) localization of aggregates (cytosol, perinuclear, or nuclear). A data table of aggregate information on a per cell basis, as well as a summary table, is provided for further data analysis. We demonstrate the versatility of AggreCount by analyzing a number of different cellular aggregates including aggresomes, stress granules, and inclusion bodies caused by huntingtin polyglutamine expansion. Full Article