Nitric oxide (NO) from endothelial NO synthase importantly contributes to vascular homeostasis. Reduced NO production or increased scavenging during disease conditions with oxidative stress contribute to endothelial dysfunction and NO deficiency. In addition to the classical enzymatic NO synthases (NOS) system, NO can also be generated via the nitrate-nitrite-NO pathway. Dietary and pharmacological approaches aimed at increasing NO bioactivity, especially in the cardiovascular system, have been the focus of much research since the discovery of this small gaseous signaling molecule. Despite wide appreciation of the biological role of NOS/NO signaling, questions still remain about the chemical nature of NOS-derived bioactivity. Recent studies show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase, and directly activate the soluble guanylyl cyclase-cGMP-protein kinase G pathway without intermediacy of free NO. Moreover, interaction between red blood cells and the endothelium in the regulation of vascular NO homeostasis have gained much attention, especially in conditions with cardiometabolic disease. In this review we discuss both classical and nonclassical pathways for NO generation in the cardiovascular system and how these can be modulated for therapeutic purposes.

The class F of G protein-coupled receptors (GPCRs) consists of 10 Frizzleds (FZD_1–10) and Smoothened (SMO). FZDs bind and are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, and SMO is indirectly activated by the Hedgehog (Hh) family of morphogens acting on the transmembrane protein Patched. The advance of our understanding of FZDs and SMO as dynamic transmembrane receptors and molecular machines, which emerged during the past 14 years since the first-class F GPCR IUPHAR nomenclature report, justifies an update. This article focuses on the advances in molecular pharmacology and structural biology providing new mechanistic insight into ligand recognition, receptor activation mechanisms, signal initiation, and signal specification. Furthermore, class F GPCRs continue to develop as drug targets, and novel technologies and tools such as genetically encoded biosensors and CRISP/Cas9 edited cell systems have contributed to refined functional analysis of these receptors. Also, advances in crystal structure analysis and cryogenic electron microscopy contribute to the rapid development of our knowledge about structure-function relationships, providing a great starting point for drug development. Despite the progress, questions and challenges remain to fully understand the complexity of the WNT/FZD and Hh/SMO signaling systems.

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites of the kynurenine pathway (KP), the major degradative cascade of the essential amino acid tryptophan in mammals, in the pathophysiology of neurologic and psychiatric diseases. A number of KP enzymes, such as tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 and IDO2), kynurenine aminotransferases (KATs), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3-HAO), and quinolinic acid phosphoribosyltransferase (QPRT), control brain KP metabolism in health and disease and are therefore increasingly considered to be promising targets for the treatment of disorders of the nervous system. Understanding the distribution, cellular expression, and regulation of KP enzymes and KP metabolites in the brain is therefore critical for the conceptualization and implementation of successful therapeutic strategies.

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HARI SREENIVASAN: President Xi Jinping opened China’s twice-per-decade Communist Party Congress today with a lengthy list of his achievements during his first five-year term, and his vision of where he hopes to take his nation.

But beyond the words, Xi is asserting power like no Chinese leader in decades.

William Brangham reports.

WILLIAM BRANGHAM: The applause, the music, it was a reception befitting the commanding role that Xi Jinping has taken since being named party leader five years ago.

He opened today’s proceedings by hailing reforms he’s put in place, and proclaiming a — quote — “new era for China.”

PRESIDENT XI JINPING, China (through interpreter): The Chinese nation has realized a great leap, from declining in modern history to twisting its fate fundamentally and continuously moving to prosperity.

WILLIAM BRANGHAM: Over 3.5 hours, Xi laid out his vision to shape the nation of 1.4 billion people into what he called a — quote — “great modern socialist country” over the next three decades.

PRESIDENT XI JINPING (through interpreter): Achieving the great rejuvenation of the Chinese nation will be no walk in the park, and it will take more than drumbeating and gong-clanging to get there. The whole party must be prepared to make more arduous, strenuous efforts.

WILLIAM BRANGHAM: Susan Shirk is chair of the 21st Century China Center at the University of California, San Diego.

SUSAN SHIRK, University of California, San Diego: Xi Jinping has a vision of China’s role in the world that is much more ambitious than anything we have seen before, talking about China kind of moving toward the center of the world and having a lot more influence than it did before.

WILLIAM BRANGHAM: In his address, Xi largely ignored the question of political reforms in China, and he didn’t mention President Trump or North Korea’s nuclear weapons program.

But in a rare move, he did acknowledge that with global demand weakening, there were challenges facing China’s export-driven economy.

PRESIDENT XI JINPING (through interpreter):  While China’s overall productive forces have significantly improved and in many areas our production capacity leads the world, the more prominent problem is that our development is unbalanced and inadequate.

WILLIAM BRANGHAM: Xi was one of the first foreign leaders to meet with President Trump.

PRESIDENT DONALD TRUMP: The relationship developed by President Xi and myself, I think, is outstanding.

WILLIAM BRANGHAM: That was decidedly warmer than Mr. Trump’s past criticism of China and its economic and trade policies.

But other U.S. officials are more critical of Beijing’s actions.

REX TILLERSON, Secretary of State: China, while rising alongside India, has done so less responsibly.

WILLIAM BRANGHAM: Secretary of State Rex Tillerson today criticized China’s aggressive displays of economic and military power, particularly its expansion on man-made islands in the South China Sea.

REX TILLERSON: We will not shrink from China’s challenges to the rules-based order, and where China subverts the sovereignty of neighboring countries and disadvantages the U.S. and our friends.

SUSAN SHIRK: I think there are things to worry about in Chinese foreign policy that are mostly related to these maritime sovereignty issues and to a kind of bullying in Asia, but the global ambition could turn out to be positive.

WILLIAM BRANGHAM: Susan Shirk says China has filled a vacuum left by the United States’ withdrawal from global agreements like the Trans-Pacific Partnership and the Paris climate accords.

Perhaps the most important thing to watch for in the next few days is who Xi establishes as his likely successor.

SUSAN SHIRK: That is why there is a lot of speculation now that he may be trying, much like Putin, to stay on beyond his normal term or to rule behind the scenes even after he retires.

WILLIAM BRANGHAM: President Trump will be traveling to Beijing to meet Xi next month.

For the PBS NewsHour, I’m William Brangham.

The post Xi Jinping celebrates China’s rising power — and his own appeared first on PBS NewsHour.

REVERB features 17 audiovisual installations including new works by Es Devlin and Theaster Gates, plus Devon Turnbull's Listening Room.

The post The Vinyl Factory celebrates art and sound with immersive exhibition at 180 Studios appeared first on Fact Magazine.

Beloved roguelike traumatic-childhood-em-up The Binding Of Issac: Rebirth turned 10 yesterday, and it’s half off on Steam to celebrate. What’s more, maker Edmund McMillen has announced that the foretold online co-op update is due on the 18th of this month, alongside a “considerable” balance update. Consider me considering the considerability of said considerable update!

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Four decades after the first IEEE International Conference on Robotics and Automation (ICRA) in Atlanta, robotics is bigger than ever. Next week in Rotterdam is the IEEE ICRA@40 conference, “a celebration of 40 years of pioneering research and technological advancements in robotics and automation.” There’s an ICRA every year, of course. Arguably the largest robotics research conference in the world, the 2024 edition was held in Yokohama, Japan back in May.

ICRA@40 is not just a second ICRA conference in 2024. Next week’s conference is a single track that promises “a journey through the evolution of robotics and automation,” through four days of short keynotes from prominent roboticists from across the entire field. You can see for yourself, the speaker list is nuts. There are also debates and panels tackling big ideas, like: “What progress has been made in different areas of robotics and automation over the past decades, and what key challenges remain?” Personally, I’d say “lots” and “most of them,” but that’s probably why I’m not going to be up on stage.

There will also be interactive research presentations, live demos, an expo, and more—the conference schedule is online now, and the abstracts are online as well. I’ll be there to cover it all, but if you can make it in person, it’ll be worth it.

Forty years ago is a long time, but it’s not that long, so just for fun, I had a look at the proceedings of ICRA 1984 which are available on IEEE Xplore, if you’re curious. Here’s an excerpt of the forward from the organizers, which included folks from International Business Machines and Bell Labs:

The proceedings of the first IEEE Computer Society International Conference on Robotics contains papers covering practically all aspects of robotics. The response to our call for papers has been overwhelming, and the number of papers submitted by authors outside the United States indicates the strong international interest in robotics.
The Conference program includes papers on: computer vision; touch and other local sensing; manipulator kinematics, dynamics, control and simulation; robot programming languages, operating systems, representation, planning, man-machine interfaces; multiple and mobile robot systems.
The technical level of the Conference is high with papers being presented by leading researchers in robotics. We believe that this conference, the first of a series to be sponsored by the IEEE, will provide a forum for the dissemination of fundamental research results in this fast developing field.

Technically, this was “ICR,” not “ICRA,” and it was put on by the IEEE Computer Society’s Technical Committee on Robotics, since there was no IEEE Robotics and Automation Society at that time; RAS didn’t get off the ground until 1987.

Tech expert Kurt “CyberGuy" Knutsson helps you honor our heroes with these powerful podcasts, audiobooks and documentaries this Veterans Day.

ALEXIS SANCHEZ returns to former club Arsenal tonight - and Manchester United fans are desperate to see him celebrate if he scores at the Emirates..

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In his latest book, The Blue on Fire: Hawaii, photographer Enzo Barracco hopes to inspire the world to protect the ocean.

<a href="https://bluetechker.com/" rel="nofollow ugc">Blue Techker</a> naturally like your web site however you need to take a look at the spelling on several of your posts. A number of them are rife with spelling problems and I find it very bothersome to tell the truth on the other hand I will surely come again again.

The experts behind Beyoncé, Kerry Washington and Serena Williams' tresses reveal their all-time favorite products for natural hair.

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Tickets for the event will go on sale on November 10, 2024, via BookMyShow

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South Korean actor Song Jae-rim died yesterday (Nov 12) at the age of 39. The Seongdong Police Station in Seoul confirmed that he was found deceased in his apartment at around 12.30pm. According to media reports, a friend whom he was supposed to meet for lunch had visited his home and reported the death. A two-page letter was reportedly found at the scene but the cause of death has not been confirmed. A police official, however, stated that there are "no signs of foul play". His wake was held at Yeouido St. Mary’s Hospital Funeral Hall at 5.30pm yesterday. His funeral will be held tomorrow at Seoul City Crematorium. Jae-rim gained popularity after starring in the 2012 drama The Moon Embracing the Sun and the 2014 reality series We Got Married. This year, he starred in two dramas — My Military Valentine and Queen Woo. Following news of his death, comedian Hong Seok-cheon and other celebrities posted tributes to Jae-rim on social media.

As a group of friends circled a hearse, chants were heard. Then, they stopped and bowed to the portrait displayed at the front of the vehicle. This was not a typical Buddhist funeral, but rather the unconventional birthday celebration of a funeral director, reported Shin Min Daily News. According to the Chinese evening daily, a video circulating online showed the friends chanting a birthday song. The hearse's interior had been decorated with balloons and a birthday banner, with the man even laying inside for photos. The clip garnered criticism from netizens, with some deeming it overboard and disrespectful to the funeral industry. In an interview with Shin Min, director of Xin An Funeral Services Chen Weisong (transliteration) explained that he had celebrated his birthday at the company's premises with his friends and family last week. Halfway through the performances by singers, his employees and business partners had surprised him with the birthday-themed hearse bearing his portrait. Chen told 8world he was not angry and did not think it was taboo. "I was too embarrassed to turn down their gesture," he said. 

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Sabra Launches New Ad Campaign.

Clayton uses an average of 40,000 tons of steel in the homes it builds annually. Find more facts about Clayton in this video.

Lomo saltado: Esta receta está llena de exquisitos sabores y texturas que le harán la boca agua a toda la familia. Ingredientes: lomo de cerdo picado en tiras, saltado con papas blancas, pimiento amarillo, pimiento Cubanelle y tomates.

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