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

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews

Jiayan Guo
Dec 1, 2020; 61:1764-1775
Research Articles

Nicholas D. LeBlond
Dec 1, 2020; 61:1697-1706
Research Articles

Astrid M. Moerman
Dec 23, 2020; 0:jlr.RA120000974v1-jlr.RA120000974
Research Articles

Jenny E. Kanter
Dec 8, 2020; 0:jlr.ILR120001217v1-jlr.ILR120001217
Images in Lipid Research

Akemi Kakino
Nov 3, 2020; 0:jlr.RA120000767v1-jlr.RA120000767
Research Articles

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.

Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of > 90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, while diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear co-localization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.

Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr^–/– mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr^–/–/Bco1^–/– mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLR^W483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-B and p38/MAPK signaling pathways.

The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice made acutely atherosclerotic by injection of AAV vector encoding a gain-of-function mutant PCSK9 (PCSK9-AAV) and WD feeding. After 6 weeks of WD feeding, mice received a daily injection of either the AMPK activator A-769662 or a vehicle control for an additional 6 weeks. Following this (12 weeks total), we assessed myeloid cell populations and differences between genotype or sex were not observed. Similarly, aortic sinus plaque size, lipid staining, and necrotic area did not differ in male and female MacKO mice compared with their littermate floxed controls. Moreover, therapeutic intervention with A-769662 showed no treatment effect. There were also no observable differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area and markers of autophagy showed no effect of either lacking AMPK signaling or AMPK activation. Our data suggest that while defined roles for each catalytic AMPK subunit have been identified, complete deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Additionally, these findings suggest that intervention with the first-generation AMPK activator A-769662 is not able to stem the progression of atherosclerosis.

Tianeptine, an addictive drug at high doses, is being sold as a dietary supplement in gas stations and convenient stores. But such products could be contaminated with metals, microorganisms or other undisclosed drugs

Watch a course video excerpt from Rise of the Superheroes: The legendary Stan Lee, creator of the Avengers, Spiderman and Iron Man, has partnered with the Smithsonian National Museum of American History to launch the first global online course about superheroes to fans around the world.

Smithsonian magazine commissioned Drew Gardner for a project that connects Black Americans today to their lost ancestry. Read about Gardner’s project and process, as well as more details about the subjects of this incredible series here: https://www.smithsonianmag.com/history/descendants-black-civil-war-heroes-wear-heritage-pride-180983397/ Video produced by Sierra Theobald. Special thanks to Drew Gardner Additional credits: Emma MacBeath, WikiTree US Black Heritage project; Ottawa Goodman, research and coordinator; Sam Dole, Penumbra Foundation; Elizabeth Zuck, set design; Calvin Osbourne, props and costume; Angela Huff, hair and make up; Diego Huerta, Lexia Krebs, behind-the-scenes filming; background prints by Fujifilm USA

The legendary Stan Lee, creator of the Avengers, Spiderman and Iron Man, has partnered with the Smithsonian National Museum of American History to launch the first global online course about superheroes to fans around the world. Register now: smithsonian.com/edx/superheroes

Photographer Drew Gardner has a passion for history. His long-term project, “The Descendants,” (https://www.drewgardner.com/descendants)  wherein he recreates famous portraits of historical figures featuring their direct offspring, is his most visible expression of this interest. But like a lot of people who study history, Gardner has in recent years begun to contemplate more deeply the question of whose stories have been judged worthy of preservation, and whose have been allowed to fade into obscurity. That was how he decided to shift his specific focus to locating and photographing Black American descendants of Civil War veterans. You can take a look at Gardner’s photographs and read magazine editor Jennie Rothenberg Gritz’s exploration of their meaning here (https://www.smithsonianmag.com/history/descendants-black-civil-war-heroes-wear-heritage-pride-180983397/) . On the latest episode of the Smithsonian podcast “There’s More to That,” (https://www.smithsonianmag.com/podcast)  I speak with Janisse Flowers and her 9-year-son, Neikoye, who are descended from the Civil War drummer boy David Miles Moore Jr. After some reflection, Janisse and her husband decided to grant Gardner’s request to photograph Neikoye dressed in a replica of Moore’s Union Army uniform. Both Janisse and Neikoye share their surprise over how this experience made them more conscious of their heritage. I’m also joined by Gardner himself, who describes the challenges—and, he hopes, the potential benefits—of asking Black Americans to revisit one of the most painful chapters of America’s history by (almost) literally stepping into their ancestors’ shoes. You can learn more about Drew and his work at his website (https://www.drewgardner.com/) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz. Music by APM Music.

The legendary Stan Lee, creator of the Avengers, Spiderman and Iron Man, has partnered with the Smithsonian National Museum of American History to launch the first global online course about superheroes to fans around the world. Taught by "The Dark Knight" producer Michael Uslan, students will go into the vaults of the Smithsonian collection and hear from industry experts. Register now (http://bit.ly/1DsdJ3W) and beginning May 5, 2015, you can become a certified expert on superheroes. Sign up for the verified certificate to earn an original piece of artwork from top artist Phil Jimenez (Wonder Woman, New X-Men) with Phil's, Stan Lee’s, and Michael Uslan’s signatures.

In 1858, the mountain was named for a Confederate general. Now, it will once again be known as "Kuwohi"

A special committee has until January 15 to finalize the design, location and funding for a monument that will be erected on the lawn of the South Carolina State House

Largest Annual Summit of Engineers and Designers to Take Place January 23-26, 2011 in San Antonio

The combined efforts of trade unions, activists and other heroes over decades paved the way for the glory of the latest Bok win, writes Terry Bell.

Many teachers scrapped their lesson plans on Monday and gave their students space to talk about Kobe Bryant.

Actor Mukesh Khanna, who played the titular role in the original show, shared the teaser of the show on his Instagram on Saturday

Nandan Nilekani, co-founder of Infosys, KP Singh, chairman emeritus at DLF, and Nikhil Kamath, co-founder of Zerodha, have been named on the 17th edition of Forbes Asia's Heroes of Philanthropy list released today.

Secretary of Transportation Nicole Majeski was joined by representatives of the Delaware State Police and AAA Mid-Atlantic on Monday at the 95/896 interchange project to call attention to the importance of safe driving in our work zones across the state. National Work Zone Awareness Week is held each April at the traditional start of construction […]

Netflix's new Biblical epic is on the way, with a trailer for "Mary" landing today. Watch.

The graft involved in trying to bring the peregrine falcon, Hawaiian crow and California condor back from the brink in the US makes for compelling reading in Feather Trails by Sophie Osborn

Title: Veterans' Painkiller Abuse Can Raise Odds for Heroin Use
Category: Health News
Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Many RNA-binding proteins (RBPs) contain low-complexity domains (LCDs) with prion-like compositions. These long intrinsically disordered regions regulate their solubility, contributing to their physiological roles in RNA processing and organization. However, this also makes these RBPs prone to pathological misfolding and aggregation that are characteristic of neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) forms pathological aggregates associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While molecular chaperones are well-known suppressors of these aberrant events, we recently reported that highly disordered, hydrophilic, and charged heat-resistant obscure (Hero) proteins may have similar effects. Specifically, Hero proteins can maintain the activity of other proteins from denaturing conditions in vitro, while their overexpression can suppress cellular aggregation and toxicity associated with aggregation-prone proteins. However, it is unclear how these protective effects are achieved. Here, we used single-molecule FRET to monitor the conformations of the aggregation-prone prion-like LCD of TDP-43. While we observed high conformational heterogeneity in wild-type LCD, the ALS-associated mutation A315T promoted collapsed conformations. In contrast, an Hsp40 chaperone, DNAJA2, and a Hero protein, Hero11, stabilized extended states of the LCD, consistent with their ability to suppress the aggregation of TDP-43. Our results link single-molecule effects on conformation to macro effects on bulk aggregation, where a Hero protein, like a chaperone, can maintain the conformational integrity of a client protein to prevent its aggregation.

Despite a significant decrease in the number of prescriptions for opioids, the opioid crisis continues, fueled in large part by the availability of the phenylpiperidine mu opioid receptor (MOR) agonist fentanyl. In contrast, the number of prescriptions for and the off-label use of gabapentinoids (gabapentin and pregabalin) has increased dramatically, with gabapentinoids commonly detected in opioid overdose victims. Although gabapentinoids can decrease the potency of the opioid receptor antagonist naloxone to reverse heroin-induced hypoventilation in male rats, the specificity and nature of interaction between gabapentinoids and MOR agonists and any potential sex difference in those interactions are not well characterized. Gabapentinoids were studied in female and male rats discriminating fentanyl (0.0032 mg/kg, i.p.) or cocaine (3.2 mg/kg, i.p.). Alone, neither gabapentin nor pregabalin significantly increased fentanyl- or cocaine-appropriate responding. In rats discriminating fentanyl, each gabapentinoid dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the left, whereas naloxone dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the right. Each gabapentinoid (100 mg/kg) significantly decreased the potency of naloxone to antagonize the discriminative stimulus effect of fentanyl or heroin. In contrast, each gabapentinoid dose-dependently shifted the cocaine and d-methamphetamine discrimination dose-effect functions to the right. There were no significant sex differences in this study. These results suggest that gabapentinoids impact the misuse of opioids, the co-use of opioids and stimulant drugs, and the increasing number of overdose deaths in individuals using opioids, stimulant drugs, and gabapentinoids in mixtures.

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

Kelley thinks like a cat. Chris experiments with broccoli. Josh sells weed with Snoop Dogg. Don't tempt the mouse.

The post RPG Cast – Episode 639: “Can We Just Kill This Guy and Get a New Hero” appeared first on RPGamer.

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

Shameless scammers trick veterans into giving personal info or cash. Tech expert Kurt “CyberGuy" Knutsson explores five common scams.

HARRY KANE is now the clear favourite to win the World Cup Golden Boot after his hat-trick against Panama..

The show originally aired on Doordarshan in 1997, became one of India’s most beloved superhero shows, running for over 450 episodes

Back in October last year, Feral Interactive announced that cross platform multiplayer was in the works for Company of Heroes …

Continue reading "‘Company of Heroes’ Mobile Multiplayer Beta Announced for Next Week on Android, Full Update Coming to iOS and Switch As Well"

St. Jude Rock �n� Roll Nashville Marathon

Northwestern Mutual Honors Moms of Childhood Cancer Patients this Mother�s Day

Also: The Great Queen Victoria Winner Ostwen Has Arrived! launches in English

This HaBO is from Krysty, who wants to find this romance: Hi, I stumbled upon your website yesterday hoping someone will help me find this book. It’s been in my head for over 10 years and I’m beginning to forget. So the book is about a heroine – Marianne or Mary – can’t quite remember, falls in love with a brooding, standoffish hero with a scarred face who stays in the dark in a big … Continue reading HaBO: Yet Another Scarred Hero, Virgin Heroine →

bHighlights:/bul class="group-list punch-points"li Indian Chief Minister M.K. Stalin announces full state honors for organ donors, recognizing