Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.

Priyanka Tripathi
Dec 30, 2020; 0:jlr.RA120001190v1-jlr.RA120001190
Research Articles

Yueming Hu
Dec 11, 2020; 0:jlr.RA120000919v1-jlr.RA120000919
Research Articles

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.

Apolipoproteins C-I, C-II and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer’s disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1. delineate apoC-I, C-II and C-III isoform profiles in CSF and plasma in a cohort of non-demented older individuals (n = 61), and 2. examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared to matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two non-sialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF, and apoC-II in plasma and CSF, was observed in individuals carrying at least one apoE E4 allele. Increased apoC-I and apoC-II truncations were  associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of E4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE E4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer’s disease pathology with apoCs processing and function in the brain.

Microtubules are polymers composed of αβ-tubulin subunits that provide structure to cells and play a crucial role in in the development and function of neuronal processes and cilia, microtubule-driven extensions of the plasma membrane that have sensory (primary cilia) or motor (motile cilia) functions. To stabilize microtubules in neuronal processes and cilia, α tubulin is modified by the posttranslational addition of an acetyl group, or acetylation. We discovered that acetylated tubulin in microtubules interacts with the membrane sphingolipid, ceramide. However, the molecular mechanism and function of this interaction are not understood. Here, we show that in human iPS cell-derived neurons, ceramide stabilizes microtubules, which indicates a similar function in cilia. Using proximity ligation assays, we detected complex formation of ceramide with acetylated tubulin in C. reinhardtii flagella and cilia of human embryonic kidney (HEK293T) cells, primary cultured mouse astrocytes, and ependymal cells. Using incorporation of palmitic azide and click chemistry-mediated addition of fluorophores, we show that a portion of acetylated tubulin is S-palmitoylated. S-palmitoylated acetylated tubulin is colocalized with ceramide-rich platforms (CRPs) in the ciliary membrane, and it is coimmunoprecipitated with Arl13b, a GTPase that mediates transport of proteins into cilia. Inhibition of S-palmitoylation with 2-bromo palmitic acid or inhibition of ceramide biosynthesis with fumonisin B1 reduces formation of the Arl13b-acetylated tubulin complex and its transport into cilia, concurrent with impairment of ciliogenesis. Together, these data show, for the first time, that CRPs mediate membrane anchoring and interaction of S-palmitoylated proteins that are critical for cilium formation, stabilization, and function. 

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms 21 January 2020 — 2:30PM TO 3:30PM Anonymous (not verified) 16 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

Minister Nunes Júnior will discuss the progress of the Angolan government’s economic stabilization plans and business reform agenda including the privatization of some state-owned enterprises. These reforms could expand Angola’s exports beyond oil and stimulate new industries and more inclusive economic growth.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Air Force Secretary Frank Kendall said the branch is looking toward confronting China, as well as unity in its ranks, and added that the service needs to retire older aircraft and programs -- and focus on ones that work.

U.S. Space Force has made public the prototypes of its new uniforms, which immediately drew comparisons to those worn in Star Trek and other science fiction franchises.

California just made school accountability much more complicated. And that's good.

Art and music lovers who attended the museum's premier event were treated to Andy Warhol's "Shadows" and live music

Read more at http://www.smithsonianmag.com/arts-culture/Hazel-Scotts-Lifetime-of-High-Notes.html In a performance filmed for World War II soldiers, Hazel Scott begins with a section from Liszt's "Hungarian Rhapsody No. 2" and ends with a jazzy tune (Army / Navy Screen Magazine).

Interactive 3D manuals increase customer appreciation and satisfaction

A woman and her husband accept the Lord after hearing the gospel from an OM team visiting the island of Sante Marie.

The impact of baseball as an outreach tool is growing far beyond the first teams that began nine years ago in Érd.

A look at the two major political parties' platforms since the first charter school law was passed shows how Democrats' positions on school choice have evolved, including increased calls for accountability.

At the James E. Van Zandt VA Medical Center in Altoona, a garden yields fresh produce such as corn, tomatoes, strawberries, zucchini and peppers. It is part of the Seed to Supper program, a Penn State Extension Master Gardener initiative that teaches adults on a limited budget how to grow their own food. For one veteran in hospice care, the garden became a lifeline.

Kenya plans to re-introduce some of the tax hikes that sparked deadly protests earlier this year, the government announced Friday, while a new deputy president was sworn in after weeks of drama.

Radhakrishnan panel has submitted its report outlining reforms in the NTA and the authorities would need the state's cooperation to implement it.

Get into the holiday spirit with Bollywood movies on popular OTT platforms! From the visually spectacular Brahmastra to the inspiring tale of Shershaah and the emotional depth of Gehraiyaan, this selection has something for everyone. Whether you’re in the mood for adventure, patriotism, or family drama, these titles bring Diwali entertainment right into your home, creating memorable experiences for all.

In order to protect consumers' interest, the government has banned use of "dark patterns" on e-commerce platforms which intend to deceive customers or manipulate their choices.

Before moving in, Ms Lalliam and her family also performed a customary 'puja' and prayer ceremony to honour the actor's spirit and legacy.

Governor Markell signed House Bill 175 which will place tighter controls on workers compensation medical costs, while improving the state’s workplace safety program and more effectively encouraging injured individuals to return to work.

Here Mudassar Khan has explained

Under Lt. Governor Hall-Long’s leadership, efficiencies to the Board of Pardons have significantly reduced wait times, streamlined processes and ultimately help Delawareans achieve stability in all aspects of life    DOVER, Del. – More Delawareans have been recommended for and been granted a pardon or commutation during the past eight years than at any point […]

Kenya’s cabinet secretary for the national treasury and planning, Ukur Yatani, discusses the country’s agenda of fiscal reforms and the importance of constructing an east-west Africa highway.

Continued African development could hinge on public finance reforms.

To provide high-quality medical care to its population — around 30% of whom are 65 or older — Japan is pursuing sovereign AI initiatives supporting nearly every aspect of healthcare. AI tools trained on country-specific data and local compute infrastructure are supercharging the abilities of Japan’s clinicians and researchers so they can care for patients, Read Article

The Federal Government, through the Ministry of Solid Minerals Development, has formalised the activities of 250 small and artisanal miners into cooperatives as part of efforts to help artisanal miners transition away from illegal mining. The Minister of Solid Minerals Development, Dele Alake, disclosed this on Tuesday at a briefing to announce the 9th edition

Online gambling platforms are always open, meaning you can gamble when you feel like it

To attract infrastructure investment to meet national goals for providing electricity to consumers, India needs continued macroeconomic stability as well as an improved policy and regulatory environment.

This paper explores how oil price windfalls impact labor market regulation across 83 countries from 1970 to 2014.

Fossils in rocks that are 3.8 billion years old have puzzled biologists as they look nothing like modern cells, but now it seems they may be an ancient precursor life form that was unable to control its structure

Today’s market likes products. Platforms aren’t in vogue anymore. Investors, especially in the public markets, only want late stage de-risked assets. Pharma only seems to be buying these kinds of asset. VCs need to focus on clinical stage companies. Or

The post Biotech Risk Cycles: Assets And Platforms appeared first on LifeSciVC.

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New program offers educators techniques and strategies for improving awareness of professional risks and vulnerabilities, and for the application of professional ethics in daily decision making.

In a pre-Budget meeting with Revenue Secretary Sanjay Malhotra, the Confederation of Indian Industry (CII) urged the government to continue tax reforms and boost capital expenditure in the Union Budget for 2025-26....

The UK tax agency has extended various deadlines for responses to consultations and for other work on tax reform, in light of COVID-19.

Singapore's Ministry of Finance has launched a public consultation on proposed corporate tax and income tax breaks.

The Dutch Government has issued a decree to ensure the country's dividend withholding tax rules comply with the European Court of Justice's ruling in the Sofina case.

The Dutch Government has issued a decree to ensure the country's dividend withholding tax rules comply with the European Court of Justice's ruling in the Sofina case.

Highlights: Robotic-assisted surgery has gained traction over the years due to its benefits It requires smaller

Following a consultation exercise, the Inland Revenue Authority of Singapore has said the territory intends to go ahead with various important goods and services tax regime changes without accepting amendments proposed by stakeholders.

Modern farming practice of rainwater storage in ancient tanks lauded as best practice adaptation strategy Bonn, Germany. 14 JUNE 2013 —Whether it’s bracing for drought in Sri Lanka with a return to ancient water storage systems or swapping coffee for cocoa in Central America, findings from a new report from the CGIAR Research Program on Climate […]

The post Sri Lankan water history informs global climate change study first appeared on International Water Management Institute (IWMI).

Intact America Blasts American Academy of Pediatrics' Call To Weaken U.S. Ban on All Forms of Female Genital Cutting as

First and only UK research centre to dedicate empathy to the heart of healthcare has set an urgent yet reforming need for patient care. Prof. Jeremy

Are you a night owl? Well, it's not a crime to be one! Many people enjoy staying up late, whether they're out partying, hanging out with friends, or just scrolling through reels and sending texts after midnight. For them, waking up