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Bali flights cancelled due to dangerous volcanic ash

Australian airlines say it is unsafe to fly after Mount Lewotobi Laki-laki spewed ash.




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Weekly football quiz: Man City's run & hat-trick heroes

It is the weekly football quiz - how closely have you been paying attention over the past seven days?





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velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :)

velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :)




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Letting Hero-Worship Go

As discussion of Emily Hanford’s new podcast builds, teachers are questioning stories we were sold by people we trusted. For some teachers, this is the first time they’ve doubted instructional materials that are ubiquitous in elementary and reading intervention classrooms. When we question the tenets of Balanced Literacy, teachers can unearth a trove of information. But how to make sense of it all?




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Sport | 'Dangerous' and 'arrogant': Rassie's latest Bomb Squad whips up fresh criticism up north

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.




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China’s zero-COVID cannot continue, reopening is needed

China’s zero-COVID cannot continue, reopening is needed Expert comment NCapeling 1 December 2022

Unsure of how to loosen rules, local officials have doubled down on severe restrictions behind so much economic damage. Reopening will quell public anger.

When President Xi Jinping was seen unmasked at the G20 summit in Indonesia, he maintained a largely positive tone with President Joe Biden and other world leaders. This left an impression that China was on the verge of withdrawing its zero-COVID strategy.

A set of loosening policy measures introduced by Beijing seemed to further suggest that China was on track to reopen. As outlined in the 20th party congress, Xi wants to forge a pathway towards economic modernization and this means building economic resilience and a further increase in household incomes.

However, a series of displays of public defiance against the government’s zero-COVID policy has left the rest of the world perplexed. Some loosening of restrictions announced on 11 November by the central government, with the number of new cases still rising rapidly, left the provincial governments in confusion as to which direction to turn.

Absolute political loyalty

The persistent slogan of ‘zero-COVID’ was in stark contrast to the slackening of restrictions. Local officials decided to double down on stringent COVID measures as a way of displaying absolute political loyalty to the top, which inevitably caused daily agonies among large parts of the Chinese population.

The strategy has intensified economic pressures, exacerbated rising levels of youth unemployment, and tested the patience of the entire country

This decision-making process sheds some light on the way the Chinese bureaucracy approaches crises at a time when the party leadership is tightening political control. Lower-level officials avoided making important decisions and instead decided to wait for instructions from the top. As the rules were unclear, they implemented policies according to past precedents, in this case zero-COVID, which had worked relatively well for China in 2020 and 2021.

For decades, local governments have been major political actors in China and have known what works best under local conditions. But with tighter regulation being exercised by lower-level bureaucrats and civil servants, there is less opportunity for the input of local knowledge, increasing the risk of ineffective policies being implemented.

Away from Beijing, those not employed by the state have been hit particularly hard by zero-COVID measures. The strategy has intensified economic pressures, exacerbated rising levels of youth unemployment, and tested the patience of the entire country.

It is difficult to see how China’s economy can crank up again until the country reduces its internal restrictions and reconnects with the world

Billions of Chinese people want to have their life return to normal without the fear of having the wrong colour – yellow or red – on their COVID health QR code or endless mandatory testing. Only a green code shows that a person is healthy and able to move around freely.

Economy is suffering

China is still balancing its twin aims of containing the spread of COVID and re-engineering its economy along similar lines to the rest of the world. It is difficult to see how China’s economy can crank up again until the country reduces its internal restrictions and reconnects with the world.




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Why burning biomass is not zero-carbon

Why burning biomass is not zero-carbon Explainer Video NCapeling 17 October 2022

Short animation explaining why burning biomass produces more carbon dioxide per unit of energy generated than almost all fossil fuels.

The climate emergency requires countries to transition away from fossil fuels, but it is important to be careful about the alternative energy sources chosen.

In particular, concern is growing over the use of biomass for energy, which is generated when wood or other plant material is burnt to generate heat and electricity. Many governments treat biomass energy as zero-carbon at the point of combustion, and subsidize it in the same way as renewables such as solar or wind, resulting in a large increase in the use of biomass for energy in the UK and the European Union (EU) over the past 15 years.

The treatment of biomass as zero-carbon in policy frameworks rests on the argument that biomass emissions will be reabsorbed by forest growth, particularly from trees planted to replace those cut down to burn.

But growing trees to maturity takes many years and, depending on the feedstock used, biomass burning increases global warming for decades to centuries. This is called the ‘carbon payback period’ – the time it takes for carbon dioxide levels to return to what they would have been if biomass had not been used.

New research from Chatham House and the Woodwell Climate Research Center calculated the real climate impact of burning US wood pellets in the UK and EU. In 2019, according to this analysis, US-sourced pellets burned for energy in the UK were responsible for between 13 million and 16 million tonnes of carbon dioxide, equivalent to the annual greenhouse gas emissions from 6-7 million passenger vehicles.

But because biomass is treated as zero-carbon, almost none of these emissions were included in the UK’s national greenhouse gas reports. And the removal of forest carbon from US forests is not included accurately in US reports, either.




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Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research




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Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol

James M. Ntambi
Sep 1, 1999; 40:1549-1558
Reviews




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Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles




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Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells

W Gamble
Nov 1, 1978; 19:1068-1070
Articles




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A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




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Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis

Chi-Liang Eric Yen
Nov 1, 2008; 49:2283-2301
Thematic Reviews




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Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Mohamad Navab
Jun 1, 2004; 45:993-1007
Thematic Reviews




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Intracellular cholesterol transport

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews




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Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews




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Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

JM Dietschy
Oct 1, 1993; 34:1637-1659
Reviews




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Apolipoprotein-mediated removal of cellular cholesterol and phospholipids

JF Oram
Dec 1, 1996; 37:2473-2491
Reviews




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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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




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Cell cholesterol efflux: integration of old and new observations provides new insights

George H. Rothblat
May 1, 1999; 40:781-796
Reviews




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Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice

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




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Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression

K Schoonjans
May 1, 1996; 37:907-925
Reviews




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Use of cyclodextrins for manipulating cellular cholesterol content

AE Christian
Nov 1, 1997; 38:2264-2272
Articles




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Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis

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




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The plasma lecithin:cholesterol acyltransferase reaction

John A. Glomset
Mar 1, 1968; 9:155-167
Reviews




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Molecular physiology of reverse cholesterol transport

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews





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Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage?

Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? 23 January 2020 — 8:30AM TO 10:00AM Anonymous (not verified) 6 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

In the context of the feasibility of reducing greenhouse gas emissions to net zero, policymakers are beginning to pay more attention to options for removing carbon dioxide from the atmosphere. A wide range of potential carbon dioxide removal (CDR) options are currently being discussed and modelled though the most prominent among them are bioenergy with carbon capture and storage (BECCS) and afforestation and reforestation.

There are many reasons to question the reliance on BECCS assumed in the models including the carbon balances achievable, its substantial needs for land, water and other inputs and technically and economically viable carbon capture and storage technologies.

This meeting will examine the potentials and challenges of BECCS in the context of other CDR and emissions abatement options. It will discuss the requisite policy and regulatory frameworks to minimize sustainability and socio-political risks of CDR approaches while also avoiding overshooting climate goals.

Attendance at this event is by invitation only.




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Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging [Protein Structure and Folding]

Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform. Although homomeric Cxs forms have been largely described functionally and structurally, the stoichiometry and arrangement of heteromeric Cx channels remain unknown. The latter, however, are widely expressed in human tissues and variation might have important implications on channel function. Investigating properties of heteromeric Cx channels is challenging considering the high number of potential subunit arrangements and stoichiometries, even when only combining two Cx isoforms. To tackle this problem, we engineered an HA tag onto Cx26 or Cx30 subunits and imaged hemichannels that were liganded by Fab-epitope antibody fragments via atomic force microscopy. For Cx26-HA/Cx30 or Cx30-HA/Cx26 heteromeric channels, the Fab-HA binding distribution was binomial with a maximum of three Fab-HA bound. Furthermore, imaged Cx26/Cx30-HA triple liganded by Fab-HA showed multiple arrangements that can be derived from the law of total probabilities. Atomic force microscopy imaging of ringlike structures of Cx26/Cx30-HA hemichannels confirmed these findings and also detected a polydisperse distribution of stoichiometries. Our results indicate a dominant subunit stoichiometry of 3Cx26:3Cx30 with the most abundant subunit arrangement of Cx26-Cx26-Cx30-Cx26-Cx30-Cx30. To our knowledge, this is the first time that the molecular architecture of heteromeric Cx channels has been revealed, thus providing the basis to explore the functional effect of these channels in biology.




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Cholesterol sensing by CD81 is important for hepatitis C virus entry [Protein Structure and Folding]

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in both health and disease.




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Unique active-site and subsite features in the arabinogalactan-degrading GH43 exo-{beta}-1,3-galactanase from Phanerochaete chrysosporium [Enzymology]

Arabinogalactan proteins (AGPs) are plant proteoglycans with functions in growth and development. However, these functions are largely unexplored, mainly because of the complexity of the sugar moieties. These carbohydrate sequences are generally analyzed with the aid of glycoside hydrolases. The exo-β-1,3-galactanase is a glycoside hydrolase from the basidiomycete Phanerochaete chrysosporium (Pc1,3Gal43A), which specifically cleaves AGPs. However, its structure is not known in relation to its mechanism bypassing side chains. In this study, we solved the apo and liganded structures of Pc1,3Gal43A, which reveal a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family 35 (CBM35) binding domain. GH43_sub24 is known to lack the catalytic base Asp conserved among other GH43 subfamilies. Our structure in combination with kinetic analyses reveals that the tautomerized imidic acid group of Gln263 serves as the catalytic base residue instead. Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite −1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the β-1,6–linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s, including those that bind galactomannan. Specifically, we noted a Gly → Trp substitution, which affects pyranose stacking, and an Asp → Asn substitution in the binding pocket, which recognizes β-linked rather than α-linked Gal residues. These findings should facilitate further structural analysis of AGPs and may also be helpful in engineering designer enzymes for efficient biomass utilization.




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Post-translational control of the long and winding road to cholesterol [Lipids]

The synthesis of cholesterol requires more than 20 enzymes, many of which are intricately regulated. Post-translational control of these enzymes provides a rapid means for modifying flux through the pathway. So far, several enzymes have been shown to be rapidly degraded through the ubiquitin–proteasome pathway in response to cholesterol and other sterol intermediates. Additionally, several enzymes have their activity altered through phosphorylation mechanisms. Most work has focused on the two rate-limiting enzymes: 3-hydroxy-3-methylglutaryl CoA reductase and squalene monooxygenase. Here, we review current literature in the area to define some common themes in the regulation of the entire cholesterol synthesis pathway. We highlight the rich variety of inputs controlling each enzyme, discuss the interplay that exists between regulatory mechanisms, and summarize findings that reveal an intricately coordinated network of regulation along the cholesterol synthesis pathway. We provide a roadmap for future research into the post-translational control of cholesterol synthesis, and no doubt the road ahead will reveal further twists and turns for this fascinating pathway crucial for human health and disease.




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Ascertaining the biochemical function of an essential pectin methylesterase in the gut microbe Bacteroides thetaiotaomicron [Metabolism]

Pectins are a major dietary nutrient source for the human gut microbiota. The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II–derived oligosaccharide ΔBT1017oligoB generated by a BT1017 deletion mutant (ΔBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of ΔBT1017oligoB using a combination of enzymatic, mass spectrometric, and NMR approaches revealed that it is a bimethylated nonaoligosaccharide (GlcA-β1,4-(2-O-Me-Xyl-α1,3)-Fuc-α1,4-(GalA-β1,3)-Rha-α1,3-Api-β1,2-(Araf-α1,3)-(GalA-α1,4)-GalA) containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an α/β-hydrolase fold, consisting of a central twisted 10-stranded β-sheet sandwiched by several α-helices. This constitutes a new fold for pectin methylesterases, which are predominantly right-handed β-helical proteins. Bioinformatic analyses revealed that the family is dominated by sequences from prominent genera of the human gut microbiota, including Bacteroides and Prevotella. Our re-sults not only highlight the critical role played by this family of enzymes in pectin metabolism but also provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut.




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Citrus Vascular Proteomics Highlights the Role of Peroxidases and Serine Proteases during Huanglongbing Disease Progression

Jessica Y. Franco
Dec 1, 2020; 19:1936-1951
Research




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Identification of novel serological autoantibodies in Takayasu arteritis patients using HuProt arrays

Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
Research




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Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous

Melissa Gómez
Dec 1, 2020; 61:1658-1674
Research Articles




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Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

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




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A novel phosphoglycerol serine-glycine lipodipeptide of Porphyromonas gingivalis is a TLR2 ligand

Frank C. Nichols
Dec 1, 2020; 61:1645-1657
Research Articles




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Human glucocerebrosidase mediates formation of xylosyl-cholesterol by {beta}-xylosidase and transxylosidase reactions.

Daphne E.C. Boer
Dec 23, 2020; 0:jlr.RA120001043v1-jlr.RA120001043
Research Articles




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Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

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




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Lipid signature of advanced human carotid atherosclerosis assessed by mass spectrometry imaging

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




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Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles




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Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition

Genta Kakiyama
Dec 1, 2020; 61:1629-1644
Research Articles




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The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis

Natalie Bruiners
Dec 1, 2020; 61:1617-1628
Research Articles




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Accessible cholesterol is localized in bacterial plasma membrane protrusions

Michael E. Abrams
Dec 1, 2020; 61:1538-1538
Images in Lipid Research




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Mutation in the distal NPxY motif of LRP1 alleviates dietary cholesterol-induced dyslipidemia and tissue inflammation

Anja Jaeschke
Dec 9, 2020; 0:jlr.RA120001141v1-jlr.RA120001141
Research Articles




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Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice

Abudukadier Abulizi
Dec 1, 2020; 61:1565-1576
Research Articles




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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux

Oktawia Nilsson
Nov 17, 2020; 0:jlr.RA120000920v1-jlr.RA120000920
Research Articles




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Apolipoprotein C3 and apolipoprotein B colocalize in proximity to macrophages in atherosclerotic lesions in diabetes

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