log Princeton archaeologists are using cutting-edge digital technologies to help reveal the ancient past By www.princeton.edu Published On :: Tue, 09 Apr 2024 14:13:00 -0400 In the field, digital technology saves immense amounts of time and limits fruitless digging. In the classroom, VR recreations help bring the past to life. Full Article
log Mapping brain function, safer autonomous vehicles are focus of Schmidt Transformative Technology fund By www.princeton.edu Published On :: Wed, 08 May 2024 15:58:00 -0400 Two projects — one that maps the function of the brain’s neuronal network in unprecedented detail and another that combines robotics and light-based computer circuits to create safe self-driving vehicles — have been awarded funding through Princeton’s Eric and Wendy Schmidt Transformative Technology Fund. Full Article
log Bloghouse-Keeping By blog.chasclifton.com Published On :: Sat, 07 Sep 2024 21:29:02 +0000 First, welcome to a bunch of new subscribers! Subscriptions are free, and you receive an email whenever I publish something On a computer or tablet, you will see the sign-up box in the right-hand sidebar. On a smartphone, you have … Continue reading → Full Article Uncategorized blogging Pagan studies
log Eric Wood, world-renowned hydrologist and ‘giant in the field,’ dies at 74 By www.princeton.edu Published On :: Fri, 10 Dec 2021 09:30:05 -0500 Eric Franklin Wood, a world-renowned hydrologist who did groundbreaking work in drought prediction and served on the Princeton faculty for 43 years, died from cancer in Brooklyn, New York, on Nov. 3. He was 74. Full Article
log Jacques Fresco, 'a major figure in the birth of modern molecular biology,' dies at 93 By www.princeton.edu Published On :: Tue, 04 Jan 2022 15:20:00 -0500 Jacques R. Fresco, the emeritus Damon B. Pfeiffer Professor in the Life Sciences and an emeritus professor of molecular biology, died on Dec. 5. He served on Princeton's faculty for 53 years before retiring in July 2013. Full Article
log Austin Newton, 'pioneer in molecular biology,' dies at 85 By www.princeton.edu Published On :: Tue, 14 Jun 2022 17:31:34 -0400 Austin Newton, a founding member of the Department of Molecular Biology, established a new experimental system and mentored generations of undergraduates, graduate students and postdoctoral fellows. He died May 13 in Princeton at age 85. Full Article
log Robert Lisk, eminent biologist and ‘kind and generous mentor,’ dies at 88 By www.princeton.edu Published On :: Fri, 19 Jan 2024 13:09:00 -0500 Lisk taught biology at Princeton for 30 years before transferring to emeritus status in 1990. Full Article
log How Modern Technology has Changed the Way we Listen to Music? By www.star2.org Published On :: Wed, 25 Jan 2023 20:35:03 +0000 From the moment the phonograph was discovered, things began to move upwards, so that today, for very little money, we could have music and even find out the name of the song we are currently listening to, with one click. Modern technology has changed the ways of listening to music. Music has never been more ... Read more The post How Modern Technology has Changed the Way we Listen to Music? appeared first on Star Two. Full Article Music Technology Bluetooth Kraftwerk Modern Technology Streaming music
log RSS Ground Change Log October 2018 By www.rssground.com Published On :: Thu, 01 Nov 2018 13:05:18 +0000 Hi! Right now we are busy with our primary project – major design update for posting campaigns editor. It will be ready really soon. But we also take time to respond to your requests and suggestions. Here is our change log for October 2018: Google+ Poster Shutting Down Since Google stops its support of Google+ […] The post RSS Ground Change Log October 2018 appeared first on RSSground.com. Full Article RSS Ground News bug fix change log service improvements service updates
log RSS Ground Changelog November 2018 By www.rssground.com Published On :: Sat, 01 Dec 2018 06:20:19 +0000 Hey there! Earlier this month we have announced a planned service maintenance. That was done in order to implement a new update we’ve been working on for the last several weeks. It includes user interface changes, new options and features, and some system changes. Please see the list of what was added below: Major interface […] The post RSS Ground Changelog November 2018 appeared first on RSSground.com. Full Article RSS Ground News bug fix change log service improvements service updates
log 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
log RSS Ground Changelog January 2019 By www.rssground.com Published On :: Thu, 07 Feb 2019 09:03:38 +0000 We have planned several new service updates for this year, and you will be seeing them very often. Here is the first in this season report about our development process. We have made several fixes and updates in January. See the list below: New Content Elements In YouTube Video Feeds We have added new content elements […] The post RSS Ground Changelog January 2019 appeared first on RSSground.com. Full Article RSS Ground News bug fix change log service improvements service updates
log 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
log RSS Ground Changelog February 2019 By www.rssground.com Published On :: Tue, 05 Mar 2019 01:43:20 +0000 We have several amazing updates added to the service last month. These updates concern both content posting and content searching tools. Below is the list of updates for the month of February: New WordPress and Blogger Posters We have completed the renovation of our main tools interfaces. We have improved and unified layouts across all of […] The post RSS Ground Changelog February 2019 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log Smart Way To Set Up Automated Blog Posting By www.rssground.com Published On :: Tue, 05 Mar 2019 02:07:21 +0000 We have already shared our thoughts on why people do blog and why blogging is still afloat despite the rise of social media. We have also reasoned the help of automated blogging and even its necessity. And after RSS Ground has updated all of its automated posters we would like to dwell in more detail […] The post Smart Way To Set Up Automated Blog Posting appeared first on RSSground.com. Full Article eBusiness Tips auto blogging automated posting blog posters blogger tools RSS to blog
log RSS Ground Changelog March 2019 By www.rssground.com Published On :: Fri, 05 Apr 2019 12:14:30 +0000 We continue to grow and improve RSS Ground. We add new features and options, provide you with more tutorials and other useful information. And of course we don’t stop developing new tools. Read about RSS Ground latest news and updates The post RSS Ground Changelog March 2019 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog June 2019 By www.rssground.com Published On :: Fri, 05 Jul 2019 12:30:22 +0000 New tools, new features, new plans! RSS Ground is evolving and developing. We have a whole bunch of exacting updates released in June. The post RSS Ground Changelog June 2019 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog October 2019 By www.rssground.com Published On :: Wed, 06 Nov 2019 00:06:54 +0000 Our service is just like a living organism, with its own worries and joys. And hope you feel the pulse of our live. Find out what we were working on lately. The post RSS Ground Changelog October 2019 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog January 2020 By www.rssground.com Published On :: Mon, 10 Feb 2020 13:35:28 +0000 Winter is outside, but it is pretty hot in our labs. We have prepared several good updates for you this January. Please enjoy and get ready for more! Content Recycle As you know, the main idea of RSS Ground posting services is gradual updates with unique content. Our posting campaigns functionality is built to ensure […] The post RSS Ground Changelog January 2020 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog February 2020 By www.rssground.com Published On :: Fri, 06 Mar 2020 14:36:24 +0000 Time flies fast, especially when you are busy doing something you like and care about. This time we have added a improved image posting to Facebook pages and groups, additional options for feed editing and a bit more clear error notifications in feeds Preview. Improved image posting to Facebook Click to enlarge Before, when you […] The post RSS Ground Changelog February 2020 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog March 2020 By www.rssground.com Published On :: Tue, 31 Mar 2020 16:33:13 +0000 RSS Ground team now works from home. But we are still efficient and productive. Here is what we did for you in March plus some of our plans for the future. YouTube Feeds Now require API key Click to enlarge Because of the new limitations at Google developers platform, search requests for YouTube videos now […] The post RSS Ground Changelog March 2020 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog April 2020 By www.rssground.com Published On :: Thu, 07 May 2020 14:39:12 +0000 Epidemic situation in the World has influenced all of us a lot. Many businesses started paying more attention to their online presence as many people started to look for more opportunities to make additional money online. Affiliate marketing is what comes to mind in such a situation. Following this trend we decided to enrich our […] The post RSS Ground Changelog April 2020 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog April 2021 By www.rssground.com Published On :: Wed, 05 May 2021 14:28:50 +0000 We are excited to share news about our latest updates and upcoming plans. A lot has been done to improve Personal Feeds functionality and interactions with the Facebook Platform. Personal feeds media files We have improved processing of media files in personal feeds. You can now see if your personal feed item contains media […] The post RSS Ground Changelog April 2021 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log RSS Ground Changelog May 2021 By www.rssground.com Published On :: Thu, 03 Jun 2021 14:39:29 +0000 We are glad to share our latest service updates with you. Some will require your closer attention, but others will just make you feel excited. Custom Categories In eBay Feeds Generator Now Custom category ID option is available for all eBay marketplaces. Find this option in the list with basic eBay categories. You can use […] The post RSS Ground Changelog May 2021 appeared first on RSSground.com. Full Article RSS Ground News affiliate program change log ebay feeds service improvements service updates
log RSS Ground Changelog February 2023 By www.rssground.com Published On :: Tue, 14 Feb 2023 20:52:52 +0000 Recently, we have released a decent chunk of updates and improvements. Below is what has been done in RSS Ground to make it better. We constantly strive to improve. IFTTT Integration For Existing Posting Campaigns Not so long ago we have introduced IFTTT platform integration. Since then, you are able to create posting campaigns and […] The post RSS Ground Changelog February 2023 appeared first on RSSground.com. Full Article RSS Ground News change log IFTTT poster Instagram feeds service improvements service updates Shopify
log RSS Ground Changelog March 2023 By www.rssground.com Published On :: Mon, 20 Mar 2023 14:33:15 +0000 We are ready with another set of updates and improvements for RSS Ground. Major update to LinkedIn Poster LinkedIn Poster update Now you can have a full control over your LinkedIn automated posts. You can optionally add item’s title, description and image to your post. Also, you can add custom text, specify call-to-action text with […] The post RSS Ground Changelog March 2023 appeared first on RSSground.com. Full Article RSS Ground News change log CJ Affiliate Feeds ClickBank Feeds LinkedIn poster service improvements service updates Twitter poster
log RSS Ground Changelog June 2023 By www.rssground.com Published On :: Mon, 10 Jul 2023 20:44:45 +0000 We are excited to announce a new round of updates and enhancements for RSS Ground. YouTube Channel Feeds We have introduced the ability to generate YouTube channel feeds using the “@channel” tag. Previously generated YouTube channel feeds will continue to function without any issues. For more information, please refer to our user guide on YouTube […] The post RSS Ground Changelog June 2023 appeared first on RSSground.com. Full Article RSS Ground News change log Instagram feeds LinkedIn poster personal feeds service improvements service updates telegram feeds youtube feeds
log RSS Ground Changelog October 2023 By www.rssground.com Published On :: Mon, 06 Nov 2023 17:23:41 +0000 Below is the list of updates and fixes made in RSS Ground recently. X (Twitter) Poster After major changes on the X (Twitter) platform, we have introduced an update to our Twitter Poster. Most options and features remain the same. However, you now need to create own Twitter apps to continue posting to your Twitter […] The post RSS Ground Changelog October 2023 appeared first on RSSground.com. Full Article RSS Ground News AI chat bot change log service improvements service updates twitter feeds Twitter poster
log RSS Ground Changelog March 2024 By www.rssground.com Published On :: Tue, 02 Apr 2024 23:56:04 +0000 Check out the latest changes and updates we added to the service in March of 2024. Test Post Option For Manual Posts Following numerous requests from our users, we have added a Test Post option to your posting campaigns. You can now run manual posts regardless of whether the posting campaign is active or paused. […] The post RSS Ground Changelog March 2024 appeared first on RSSground.com. Full Article RSS Ground News change log personal feeds Posting automation service improvements service updates Test post
log RSS Ground Changelog May 2024 By www.rssground.com Published On :: Thu, 06 Jun 2024 20:00:54 +0000 Check out the latest changes and updates we added to the service in May of 2024. Personal Feeds As Triggers In Automation Platforms We have integrated Personal Feeds as a trigger in all three automation platforms: Zapier, IFTTT, and Pabbly Connect. Think of it as a mini posting campaign with just one content feed that […] The post RSS Ground Changelog May 2024 appeared first on RSSground.com. Full Article RSS Ground News change log service improvements service updates
log 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
log The perfect weekend in Bologna, Italy's underrated foodie capital By www.telegraph.co.uk Published On :: Sat, 19 Oct 2024 13:00:00 GMT Full Article structure:travel/restaurants structure:travel/nightlife structure:travel/hotels structure:travel/destination-guides-100 structure:travel structure:travel/attractions storytype:standard structure:better-life/better-life-evergreen structure:eg-general structure:better-life/better-life-guide
log Top Urology Conferences to Attend in 2024 ─ Key Events for Professionals By www.star2.org Published On :: Tue, 20 Aug 2024 08:43:03 +0000 Amid the countless challenges that healthcare professionals face daily, the pursuit of knowledge often shines as a beacon of hope. For those in the field of urology, attending conferences can be a transformative experience, merging education with the invaluable exchange of ideas. Imagine stepping into a room filled with experts who share the same passion ... Read more The post Top Urology Conferences to Attend in 2024 ─ Key Events for Professionals appeared first on Star Two. Full Article Health Key Events Top Conferences Urology Conferences
log Daily life on the International Space Station: A Q&A with a space archaeologist By www.pbs.org Published On :: Mon, 09 May 2022 17:55:00 +0000 Archaeologists are working to understand how astronauts really use their space on the ISS—and help improve space habitats of the future. Full Article
log Repeat Signage Blog By www.repeatsoftware.com Published On :: Fri, 26 Mar 2021 18:02:39 GMT You can keep up-to-date with the latest digital signage blog, Repeat Signage news and information. Full Article
log India Abraham: Healing physical and psychological scars through medical tattooing By www.jpost.com Published On :: Sun, 10 Nov 2024 08:41:01 GMT Jerusalemite of the week: India Abraham is a practitioner of medical tattooing who had already helped scores of people before Oct. 7, but her work has taken on even greater significance since then. Full Article health cancer Tattoos Beauty Jerusalemite of the Week
log O holograma em vitrine da Holanda usado para tentar desvendar assassinato de prostituta By www.bbc.com Published On :: Mon, 11 Nov 2024 11:55:04 GMT A morte por esfaqueamento de uma jovem húngara, assassinada logo após dar à luz, intriga a polícia há 15 anos. Full Article
log Divã em alta: por que tantas pessoas estão virando psicanalistas ou psicólogas? By www.bbc.com Published On :: Tue, 12 Nov 2024 17:54:56 GMT O Censo da Educação Superior aponta que a procura por cursos de psicologia disparou no Brasil. Entre 2010 e 2021, o aumento de matrículas nessa graduação foi de 112,4%. Full Article
log How Long To Let Logs Sit Before Splitting? By patriotoutdoornews.com Published On :: Tue, 12 Sep 2023 17:38:28 +0000 When it comes to splitting logs for firewood or other woodworking projects, patience is a virtue. While it might be tempting to start splitting freshly cut logs right away, it’s essential to allow them some time to “season” or dry out properly. The question many enthusiasts ask is, “How long should I let logs sit […] The post How Long To Let Logs Sit Before Splitting? appeared first on Patriot Outdoor News. Full Article Firewood
log How a hologram is being used to solve a sex worker's murder By www.bbc.com Published On :: Sun, 10 Nov 2024 01:22:20 GMT The fatal stabbing of a Hungarian teenager, killed shortly after she gave birth, has baffled police for 15 years. Full Article
log Paleontologist rates 14 dinosaur attacks in the "Jurassic Park" movies By www.businessinsider.com Published On :: Tue, 12 Nov 2024 19:00:02 +0000 Paleontologist Dave Hone rates the realism of the dinosaur attacks in the "Jurassic Park" and "Jurassic World" movies. Full Article Entertainment video video-format-how-real-is-it how-real-is-it movies dinosaurs paleontology jurassic-park jurassic-world jurassic-world-2 jurassic-world-3 jurassic-world-dominion jurassic-world-fallen-kingdom jurassic-park-2 jurassic-park-3 steven-spielberg laura-dern sam-neill jeff-goldblum chris-pratt bryce-dallas-howard ja-bayona science julianne-moore vince-vaughn william-h-macy new-this-week-video
log Jude Law is married to a psychologist and says talking about feelings helps maintain their 'healthy relationship' By www.businessinsider.com Published On :: Wed, 13 Nov 2024 03:30:20 +0000 Jude Law added that people in middle age should start to reflect on their relationship patterns. Full Article Health Entertainment relationship celebrity-relationships jude-law communication relationship-advice psychology
log Beyond Labels and Agendas: Research Teachers need to Know about Phonics and Phonological Awareness By www.readingrockets.org Published On :: Tue, 10 Jan 2023 16:16:51 EST This article describes the current findings on phonics and phonological awareness instruction. It uses a question & answer format to explore 10 common questions that teachers ask about teaching phonics and phonemic awareness. Here are a few key questions addressed in the article: What are phonics and phonemic awareness? Should phonemic awareness be paired with print and taught together? Should phonological awareness be coordinated with phonics instruction? What is the best sequence for teaching phonics? Full Article
log News24 Business | Samsung issues rare apology for poor results in tech 'crisis' By www.news24.com Published On :: Wednesday Oct 09 2024 09:38:21 Samsung Electronics issued a rare apology and acknowledged on Tuesday it was facing a "crisis" over its technological competitiveness, reflected in a disappointing profit guidance, despite a global AI boom. Full Article
log Technology, Humanity, and the Existential Test By battellemedia.com Published On :: Wed, 07 Aug 2024 15:58:51 +0000 I’m still digging through some of the pieces I posted at the now defunct NewCo Shift, and found this piece, adapted from a talk I gave at the Thrival Humans X Tech conference in Pittsburgh back in September of 2018. I was alarmed by trends that I saw intensifying – a push by the tech … Continue reading "Technology, Humanity, and the Existential Test" Full Article AI Columns Internet Big Five Joints After Midnight & Rants Media/Tech Business Models ai algorithms Capitalism policy politics technocapitalism technooptimism
log Analysis of {beta}-lactone formation by clinically observed carbapenemases informs on a novel antibiotic resistance mechanism [Enzymology] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism. Full Article
log Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the {alpha}/{beta}-fold epoxide hydrolase Alp1U [Enzymology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases. Full Article
log Structure, mechanism, and regulation of mitochondrial DNA transcription initiation [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus. Full Article
log The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2 [Computational Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation. Full Article
log [4Fe-4S] cluster trafficking mediated by Arabidopsis mitochondrial ISCA and NFU proteins [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins. Full Article