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Driving Small and Medium-Sized Enterprise Participation in Global Value Chains: Evidence from India

Financial constraints are a significant barrier for India's SMEs participating in global value chains.




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Firm Size and Participation in the International Economy: Evidence from Bangladesh

Export performance and firm size have a positive impact on trade participation at the intensive margin for firms of all sizes.




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Leveraging Private Sector Participation to Boost Environmental Protection in the People’s Republic of China

This brief presents recommendations to further encourage public-private partnerships for the environmental protection industry in the People's Republic of China, as the country seeks to address the negative impact of rapid urbanization.




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The Determinants of Participation in Global Value Chains: A Cross-Country, Firm-Level Analysis

High labor productivity, a large firm size, foreign ownership, and high technological capability are important for a firm to participate in global value chains.




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Driving Small and Medium-Sized Enterprise Participation in Global Value Chains: Evidence from India

Financial constraints are a significant barrier for India's SMEs participating in global value chains.




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Firm Size and Participation in the International Economy: Evidence from Bangladesh

Export performance and firm size have a positive impact on trade participation at the intensive margin for firms of all sizes.




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Howrah Municipal Corporation announces partial waiver of property and commercial tax

HOWRAH: With an eye on boosting revenue, the Howrah Municipal Corporation announced a partial waiver for property and commercial tax on Tuesday. Under the waiver scheme, no penalty or interest need to be paid. The KMC has already enforced such a scheme and has benefited greatly, said Howrah mayor Rathin Chakraborty. He said the last board, controlled by the Left Front, bungled in tax collection, resulting in tax default of around Rs 200 crore. “The state is supporting us, but we must be self-sufficient. The tax outstanding will be collected without burdening civilians,” the mayor added. http://timesofindia.indiatimes.com/city/kolkata/Howrah-Municipal-Corporation-announces-partial-waiver-of-property-and-commercial-tax/articleshow/31431111.cms




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HARMAN signs agreement to acquire entertainment lighting company Martin Professional

STAMFORD, CT – HARMAN, the global premium audio and infotainment group (NYSE:HAR), said today that it has reached an agreement to acquire Martin Professional A/S of Denmark, a world leading provider of lighting solutions for the entertainment, architectural, and commercial sectors, for EUR 110 million. The deal is subject to regulatory approvals and customary closing conditions, and is expected to close early in 2013.




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HARMAN Completes Acquisition of Entertainment Lighting Company Martin Professional

STAMFORD, CT – Continuing its strategy of delivering exceptional professional audio and entertainment products to markets worldwide, HARMAN, announced today it has completed its acquisition of Martin Professional A/S of Denmark. Martin is a world leading provider of lighting solutions for the entertainment, architectural, and commercial sectors, and its acquisition advances HARMAN’s capacity to serve customers in a wide variety of applications and geographic markets with the most advanced, highly integrated AV and lighting systems.




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Strange particles found in Antarctica cannot be explained by physics

A NASA science balloon picked up two high-energy particles and a new analysis reveals that they can't be explained by the standard model of particle physics




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Beijing gym-goers welcome partial re-open

The grunts, groans and the sound of pulsing music and crashing weights has returned to some of Beijing's gyms after being closed for nearly three months due to the coronavirus outbreak. Ciara Lee reports.




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South Korean artist crafts cornstarch furniture

Artist Ryu Jong-dae experiments with various cornstarch-based bioplastic in the bid to protect the Earth. Rosanna Philpott reports.




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Starting up in China? Here's what's most ripe for disruption

There's no doubt China's tech sector is heating up, but not all opportunities are made equal. 500 Startups' China partner Rui Ma tells Reuters' Jon Gordon where she sees the most promise




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'Full-flower supermoon' rises on world starting to emerge from lockdowns

The last "supermoon" of 2020 rose in the night sky on Thursday over a world beginning to re-emerge after weeks of coronavirus-related lockdowns.




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With just a canary for company, Russian artist self-isolates in gallery

When an art gallery in southern Russia closed its doors to help curb the spread of the coronavirus, one artist asked to self-isolate there rather than leave his place of work.




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In dress of giant inflatable roses, Chinese artist marks Earth Day

Wearing a dress she made of eight giant plastic inflatable roses over a wire structure and a headpiece crowned by a globe, Chinese performance artist Kong Ning is using fashion to draw attention to environmental protection on Earth Day.




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Spray it, don't say it: Kenya graffiti artists spread health message

A six-foot image of a sad-eyed man, baseball cap askew and mask covering his nose and mouth is spray painted on a building in a Nairobi slum. Next to it are the words “Corona is real”.




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Cuba's artists make music and dance on rooftops during lockdown

Cuba's artists are rising to the occasion during the coronavirus lockdown, taking to rooftops and balconies to create music or dance.




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Artist Banksy pays superhero tribute to Britain's NHS staff

A young boy chooses a nurse as the superhero he wants to play with over Batman and Spiderman in a new artwork by Banksy that encapsulates the gratitude Britons have felt toward the country's National Health Service during the coronavirus crisis.




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None more unbeatable than Djokovic at his best, says Martin

There is no one more unbeatable in men's tennis than Novak Djokovic when the Serb is at his best, former world number four American Todd Martin has said.




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Beijing gym-goers welcome partial re-open

The grunts, groans and the sound of pulsing music and crashing weights has returned to some of Beijing's gyms after being closed for nearly three months due to the coronavirus outbreak. Ciara Lee reports.




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Artificial Cervical Disc Surgery Cheaper Than Fusion

Title: Artificial Cervical Disc Surgery Cheaper Than Fusion
Category: Health News
Created: 4/29/2008 2:00:00 AM
Last Editorial Review: 4/29/2008 12:00:00 AM




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Bioartificial Kidney Cuts Death Risk, Improves Outcomes

Title: Bioartificial Kidney Cuts Death Risk, Improves Outcomes
Category: Health News
Created: 5/1/2008 2:00:00 AM
Last Editorial Review: 5/1/2008 12:00:00 AM




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Martial Arts Training May Save Seniors' Hips

Title: Martial Arts Training May Save Seniors' Hips
Category: Health News
Created: 4/23/2010 10:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM




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Artificial Legs Now a Reality for Pets

Title: Artificial Legs Now a Reality for Pets
Category: Health News
Created: 4/29/2010 4:10:00 PM
Last Editorial Review: 4/30/2010 12:00:00 AM




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Psychiatric Scars of Wartime Brain Injury May Linger for Years

Title: Psychiatric Scars of Wartime Brain Injury May Linger for Years
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM




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Artificial Hand 'Sees' Objects

Title: Artificial Hand 'Sees' Objects
Category: Health News
Created: 5/4/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM




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Multisociety Roadmap for Restarting Elective Cardiac Cases

A new consensus document provides guidance on the safe reintroduction of cardiovascular procedures and testing derailed by the COVID-19 pandemic.




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First-Ever Journal Article Tag Suite Conference (JATS-Con) to be Held in November 2010

PMC is pleased to announce the first of what we hope will be an annual series of conferences for users of the Journal Article Tag Suite, that is, for users of any of the “NLM DTDs”. The Journal Article Tag Suite Conference (JATS-Con) is a peer-reviewed conference that will feature a broad range of content on the Tag Suite—from the technical components to publishing theory—as well as the latest news on the Tag Suite. The conference will be hosted by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine on the NIH campus in Bethesda, Maryland on November 1 & 2, 2010.

For more information on the conference, see https://jats.nlm.nih.gov/jats-con.

Note: There is no charge for the conference; however, space is limited so preregistration is required.




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Search for Open Access Articles by License

You can now search for Open Access articles that have certain types of licenses, by using special filters in both PMC and PubMed. These filters are based on license information that is provided to PMC by publishers and other content providers, as encoded by machine-readable identifiers in the source XML of each article. For more information, see our updated Open Access Subset page.




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Three Million Articles are Now in PMC!!

As of February 21, 2014, PMC became home to three million articles! As listed on our home page, the content has been provided in part by 1441 full participation journals, 277 NIH Portfolio journals and 2470 selective deposit journals. For related information on PMC milestones, see these announcements from 2007 and 2010, respectively.




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Full text now available for OA subset articles, in plain text format

In order to facilitate text and data mining for articles in the Open Access Subset, we are now providing plain text files for those articles on our FTP site. These files contain the full text of the article, extracted either from the XML source files, or (for those articles that don't have XML) the PDF files. Users are directly and solely responsible for compliance with copyright restrictions and are expected to adhere to the terms and conditions defined by the copyright holder (see the PMC Copyright Notice).

These text files are bundled in gzipped archives. Note that these files are quite large (each greater than one gigabyte). They are available for download as:

These files are updated every week, on Saturday.

For more information, see the Bulk Packages of OA Articles section of our FTP Service page.




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Article Display Updates

In collaboration with Europe PMC, PMC has rolled out several updates to our article display in order to enhance the transparency and readability of the content.

Navigating from the PMC record to the PubMed record has been made easier by the addition of hyperlinked PubMed IDs (PMIDs) in the upper right-hand corner of article records. Clicking the PMID link will take you to the corresponding citation record in PubMed.

The PMC Disclaimer link has also been moved out of the Copyright and License information section for easier discovery and access. This page describes what content is included in PMC as well as other important NCBI and NLM disclaimer information.

Additionally, two changes have been implemented to improve the functionality of author names. Users can now click on an author name to view the author’s affiliation(s). Users also have the option of running a quick author name search in PMC by clicking the linked author name in “Find articles by [author name]”. In the example pictured above, the search would be for “Sawyer SL”[Author].

And finally, figures and tables have been moved inline in the article display. By moving away from the thumbnail display, PMC hopes to make it easier for users to view figure and table data as they read articles. Users may still click on the figure/table title or “Open in separate window” (as available) link for a closer look.

We hope these updates improve the overall user experience in PMC and look forward to hearing your feedback.

References

Screenshots from:

Qiao, Y., Yang, J., Liu, L., Zeng, Y., Ma, J., Jia, J., … Wang, Y. (2018). Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for advanced primary hepatic angiosarcoma: a case report. BMC Cancer, 18, 212. http://doi.org/10.1186/s12885-018-3996-3

Stabell, A. C., Meyerson, N. R., Gullberg, R. C., Gilchrist, A. R., Webb, K. J., Old, W. M., … Sawyer, S. L. (2018). Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir. eLife, 7, e31919. http://doi.org/10.7554/eLife.31919

Both articles made available under a CC-BY license.




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Updated information on journal selection and participation agreements released

PMC has released expanded information about its selection process for journals that apply for participation. The current review process has been in place since November 2014 and focuses on the scientific rigor and editorial quality of each journal that applies to participate in PMC. Some of the attributes taken into account as part of this process include the article content, journal policies, language quality, and presentation of content. The same assessment considerations are used for reevaluation of currently participating journals. We encourage you to visit the Journal Selection for PMC page to learn more.

Publishers and journals interested in submitting an application to PMC are also encouraged to review our updated policies on agreement types. These policies provide the eligibility criteria for each type of participation agreement and should be considered alongside the pre-application requirements.

We hope these updates are informative and look forward to hearing your feedback.




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What Is a Partial Gastrectomy?

Title: What Is a Partial Gastrectomy?
Category: Procedures and Tests
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM




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Selected Articles from This Issue




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Top-Cited Articles from Dental Education Journals, 2009 to 2018: A Bibliometric Analysis

The number of citations an article receives is an important indicator to quantify its influence in its field. The aim of this study was to identify and analyze the characteristics of the 50 top-cited articles addressing dental education published in two journals dedicated to dental education (European Journal of Dental Education and Journal of Dental Education). The Web of Science database was searched to retrieve the 50 most-cited articles from the two journals in December 2018. The top-cited articles were analyzed for journal of publication, number of citations, institution and country of origin, year of publication, study type, keywords, theme and subtheme, and international collaborations. The results showed the 50 top-cited articles were cited between 24 and 146 times each. The majority of these top-cited articles (n=34) were published in the Journal of Dental Education. Half (n=25) of the articles were by authors in the U.S. The most common study types were surveys (n=26) and reviews (n=10). The main themes of these top-cited articles were curriculum and learner characteristics. This bibliometric analysis can serve as a reference for recognizing studies with the most impact in the scholarship of dental education.




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SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles]

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.




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Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles]

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.




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A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles]

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­




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Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids [Research Articles]

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.




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Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation [Research Articles]

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.




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Slc43a3 is a regulator of free fatty acid flux [Research Articles]

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.




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The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase [Research Articles]

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.




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Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles]

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.




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Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice [Research Articles]

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRMyeLDLR–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRMyeLDLR–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRMyeLDLR–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.




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The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews]

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.




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Snake Deltavirus Utilizes Envelope Proteins of Different Viruses To Generate Infectious Particles

ABSTRACT

Satellite viruses, most commonly found in plants, rely on helper viruses to complete their replication cycle. The only known example of a human satellite virus is the hepatitis D virus (HDV), and it is generally thought to require hepatitis B virus (HBV) to form infectious particles. Until 2018, HDV was the sole representative of the genus Deltavirus and was thought to have evolved in humans, the only known HDV host. The subsequent identification of HDV-like agents in birds, snakes, fish, amphibians, and invertebrates indicated that the evolutionary history of deltaviruses is likely much longer than previously hypothesized. Interestingly, none of the HDV-like agents were found in coinfection with an HBV-like agent, suggesting that these viruses use different helper virus(es). Here we show, using snake deltavirus (SDeV), that HBV and hepadnaviruses represent only one example of helper viruses for deltaviruses. We cloned the SDeV genome into a mammalian expression plasmid, and by transfection could initiate SDeV replication in cultured snake and mammalian cell lines. By superinfecting persistently SDeV-infected cells with reptarenaviruses and hartmaniviruses, or by transfecting their surface proteins, we could induce production of infectious SDeV particles. Our findings indicate that deltaviruses can likely use a multitude of helper viruses or even viral glycoproteins to form infectious particles. This suggests that persistent infections, such as those caused by arenaviruses and orthohantaviruses used in this study, and recurrent infections would be beneficial for the spread of deltaviruses. It seems plausible that further human or animal disease associations with deltavirus infections will be identified in the future.

IMPORTANCE Deltaviruses need a coinfecting enveloped virus to produce infectious particles necessary for transmission to a new host. Hepatitis D virus (HDV), the only known deltavirus until 2018, has been found only in humans, and its coinfection with hepatitis B virus (HBV) is linked with fulminant hepatitis. The recent discovery of deltaviruses without a coinfecting HBV-like agent in several different taxa suggested that deltaviruses could employ coinfection by other enveloped viruses to complete their life cycle. In this report, we show that snake deltavirus (SDeV) efficiently utilizes coinfecting reptarena- and hartmaniviruses to form infectious particles. Furthermore, we demonstrate that cells expressing the envelope proteins of arenaviruses and orthohantaviruses produce infectious SDeV particles. As the envelope proteins are responsible for binding and infecting new host cells, our findings indicate that deltaviruses are likely not restricted in their tissue tropism, implying that they could be linked to animal or human diseases other than hepatitis.




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Magnaporthe oryzae Auxiliary Activity Protein MoAa91 Functions as Chitin-Binding Protein To Induce Appressorium Formation on Artificial Inductive Surfaces and Suppress Plant Immunity

ABSTRACT

The appressoria that are generated by the rice blast fungus Magnaporthe oryzae in response to surface cues are important for successful colonization. Previous work showed that regulators of G-protein signaling (RGS) and RGS-like proteins play critical roles in appressorium formation. However, the mechanisms by which these proteins orchestrate surface recognition for appressorium induction remain unclear. Here, we performed comparative transcriptomic studies of Morgs mutant and wild-type strains and found that M. oryzae Aa91 (MoAa91), a homolog of the auxiliary activity family 9 protein (Aa9), was required for surface recognition of M. oryzae. We found that MoAA91 was regulated by the MoMsn2 transcription factor and that its disruption resulted in defects in both appressorium formation on the artificial inductive surface and full virulence of the pathogen. We further showed that MoAa91 was secreted into the apoplast space and was capable of competing with the immune receptor chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immune responses. In summary, we have found that MoAa91 is a novel signaling molecule regulated by RGS and RGS-like proteins and that MoAa91 not only governs appressorium development and virulence but also functions as an effector to suppress host immunity.

IMPORTANCE The rice blast fungus Magnaporthe oryzae generates infection structure appressoria in response to surface cues largely due to functions of signaling molecules, including G-proteins, regulators of G-protein signaling (RGS), mitogen-activated protein (MAP) kinase pathways, cAMP signaling, and TOR signaling pathways. M. oryzae encodes eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), and MoRgs1, MoRgs3, MoRgs4, and MoRgs7 were found to be particularly important in appressorium development. To explore the mechanisms by which these proteins regulate appressorium development, we have performed a comparative in planta transcriptomic study and identified an auxiliary activity family 9 protein (Aa9) homolog that we named MoAa91. We showed that MoAa91 was secreted from appressoria and that the recombinant MoAa91 could compete with a chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immunity. By identifying MoAa91 as a novel signaling molecule functioning in appressorium development and an effector in suppressing host immunity, our studies revealed a novel mechanism by which RGS and RGS-like proteins regulate pathogen-host interactions.




arti

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