Tesla CEO Elon Musk threatened Saturday to pull the company's factory and headquarters out of California in an escalating spat with local officials who have stopped the company from reopening its electric vehicle factory.

Brandon Newman's stock rose considerably in the past six months. The 2019 guard from Valparaiso will play at Montverde (Florida) Academy as a senior.

Robert Marve, who quarterbacked Purdue to the 2012 Heart of Dallas Bowl, has been accused of battery and sexual assault in Florida.

Use our tool to check the meaning of key words and phrases associated with the Covid-19 outbreak.

The BBC speaks to unexpected sources who are supplying PPE amid coronavirus shortages.

A polar vortex has blasted into the northeastern US this weekend bringing rare May snowfall and record low temperatures to some areas.

Filed under: Food and Drink, North America, United States

• Regardless of the area's suitability for growing grapes, plop down a vineyard or winery and travelers will come for a taste and buy a sympathy bottle (pro tip: go for the ice wine as it's harder to mess up)
• Ski resorts looking to attract off-season dollars or stale attractions looking to draw media coverage and visitors hook up a zipline

Continue reading Vineyard and Zipline Trends Collide at the Pinot Express

Vineyard and Zipline Trends Collide at the Pinot Express originally appeared on Gadling on Wed, 11 Dec 2013 16:54:00 EST. Please see our terms for use of feeds.

Two-time women's World Cup winner Alex Morgan and husband Servando Carrasco have welcomed a new player to their team.

Williams driver George Russell is enjoying sim racing online while Formula 1 is suspended but admits he doesn't get the same sense of speed or fear.

After six weeks of negotiating, the UN Security Council was close to agreeing on a resolution for a global ceasefire during the Covid-19 pandemic. Seems fair, right? Let's agree to stop killing each other for a while, so we can focus on the virus that's killing us instead?

China proposed that the text explicitly mention a commitment by member nations to support the efforts of the World Health Organization — who Donald Trump has blamed (without evidence) for withholding information on the coronavirus outbreak.

So the US looked at the resolution and said "LOL no," despite last minute efforts to reach a compromise. As The Guardian reports:

On Thursday night, French diplomats thought they had engineered a compromise in which the resolution would mention UN “specialized health agencies” (an indirect, if clear, reference to the WHO).

The Russian mission signaled that it wanted a clause calling for the lifting of sanctions that affected the delivery of medical supplies, a reference to US punitive measures imposed on Iran and Venezuela. However, most security council diplomats believed Moscow would withdraw the objection or abstain in a vote rather than risk isolation as the sole veto on the ceasefire resolution.

While everyone else seemed game to go along with these compromises, the US insisted it was one big Chinese trick. As one diplomat told CNN:  "This discussion has been taken hostage by issues that do not have to do with the real issues at stake. Instead it has been transformed into a fight between the US and China. Read the rest

The DML News App offers the best in news reporting.

The post REPORT: Prominent Task Force member, CDC director to quarantine after COVID-19 exposure appeared first on Dennis Michael Lynch.

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The post REPORT: Airline to suspend service to nearly a dozen US airports starting next week appeared first on Dennis Michael Lynch.

As Quebec begins to reopen schools and businesses, Prime Minister Justin Trudeau said he’s ‘worried’ about the province’s deconfinement plans, particularly in Montreal.

The city says couples can book its Helena Gutteridge Plaza at City Hall for just $85 and bring eight guests to have an outdoor, physically distant wedding ceremony.

The manager of a Vancouver barber shop warns that once many B.C. salons are back open, they may have to implement a price increase for their services.

Many in the region had to dust off their snow shovels for at least one more dig out on Saturday morning after a polar vortex blasted parts of the province, catching many off guard.

The following article, Witness Tampering? Asst. HHS Secretary Releases Threatening Text Messages From Dem Rep. Eric Swalwell: “In clear violation of House Ethics rules “, was first published on 100PercentFedUp.com.

Now that Michael Caputo, who was previously a target of the Mueller investigation, has been cleared, he has released some pretty damning text messages from the virulently anti-Trump lawmaker from California, Rep. Eric Swalwell (D). The text messages appear to prove that Swalwell, who has spent the last 3 1/2 years calling for Trump’s impeachment, […]

Continue reading: Witness Tampering? Asst. HHS Secretary Releases Threatening Text Messages From Dem Rep. Eric Swalwell: “In clear violation of House Ethics rules “ ...

Some Buckeyes are not comfortable being told by a "woman in power" to quarantine, one expert said.

"I think it's always important to think about suicide as individual vulnerabilities and context," Eric Caine said.

(University of Stirling) A new University of Stirling study is seeking to understand how the easing of COVID-19 pandemic restrictions on licensed premises can be effectively managed to protect emergency services.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.

Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980. Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex vivo model of angiogenesis. Exposure of the aortic rings embedded in 3D fibrillar collagen to recombinant endorepellin for 2–4 h activated PERK and induced GADD45α vis à vis vehicle-treated counterparts. Similar effects were obtained with the established cellular stress inducer tunicamycin. Notably, chronic exposure of aortic rings to endorepellin for 7–9 days markedly suppressed vessel sprouting, an angiostatic effect that was rescued by blocking PERK kinase activity. Our findings unravel a mechanism by which an extracellular matrix protein evokes stress signaling in endothelial cells, which leads to angiostasis.

Since 1970, the immigrant populations from Mexico and Central America living in the United States have increased significantly: rising by a factor of 20 even as the total U.S. immigrant population increased four-fold over the period. This demographic report examines the age, educational, and workforce characteristics of these immigrants.

This report analyzes prenatal behaviors and birth outcomes of Black immigrant mothers, and finds that Black immigrant mothers are less likely to give birth to preterm or low-birth-weight infants than U.S.-born Black women, but more likely to experience these birth outcomes than other immigrant and U.S.-born women.

GEORGETOWN, Guyana (CMC): THE CARIBBEAN Community (CARICOM) Council for Human and Social Development (COHSOD) on Education says regional students will sit the Caribbean Examinations Council-administered exams in July. The COHSOD meeting, which was...

This edited volume addresses the impact of the economic crisis in seven major immigrant-receiving countries: the United States, Germany, Ireland, Portugal, Spain, Sweden, and the United Kingdom. 

A webinar showcasing MPI's profiles of unauthorized immigrants in the 94 U.S. counties with the largest populations potentially eligible for DACA or DAPA, and the implications of the data for implementation of the DACA and DAPA programs.

This is the latest in NCIIP’s language access webinar series exploring the policy and program implementation imperatives for government and community agencies serving Limited English Proficient (LEP) populations.

This webinar from the MPI’s National Center on Immigrant Integration Policy and the U.S. Conference of Catholic Bishops’ Bridging Refugee Youth & Children’s Services program explores federal requirements for providing interpretation and translation in schools and how select school districts in Minnesota and Colorado have managed these requirements.

A broad consensus exists that the long-term impact of immigration on Americans' average income is small but positive, improving employment, productivity, and income. In the short term, however, immigration may slightly reduce native employment and average income. This report provides an analysis of short- and long-run impacts of immigration over the business cycle.

The release event for MPI’s book, Migration and the Great Recession: The Transatlantic Experience, which reviews how the financial and economic crisis of the late 2000s marked a sudden and dramatic interruption in international migration trends, and the effects of the economic turmoil on immigrant workers in major immigrant-receiving countries in Europe as well as the United States.

New research demonstrates an extreme form of inattentional blindness in which we fail to see the unexpected

There’s much more to visual perception than meets the eye. What we see is not merely a matter of patterns of light falling on the retina, but rather is heavily influenced by so-called ‘top-down’ brain mechanisms, which can alter the visual information, and other types of sensory information, that enters the brain before it even reaches our conscious awareness.

Related: Memory contaminates perception | Mo Costandi

Related: Language boosts invisible objects into visual awareness | Mo Costandi

Feminism is a lie and useless in modern America, patriarchy is a good thing and natural order of society. Women be like I'm oppressed cause I don't always get my way and choose careers that pay less

I'll try to keep this short: So I have always dated guys. Yet when I am not dating guys, my best friend and I; who's a girl, hook up. We've been doing this for about 5 years, we met at the age of 15, and 5 yrs later I had my first lesbian experience with her, and then 5 years it became a fairly regular thing. 5 years is obviously a long time. But when I'm not dating a guy, I always go back to her. And she's the only woman I have ever been with. That's why I am confused about this. I do not know if I'm straight or a lesbian?

In the absence of new U.S. immigration reform legislation, this report examines the opportunities that exist within the executive branch and the administration to refine and strengthen current U.S. immigration laws and policies. The administration can exercise its authority to field policies, programs, and procedures that are effective and fair in advancing the goals of the U.S. immigration system. 

Testimony of MPI President Demetrios G. Papademetriou before the House Judiciary’s Subcommittee on Immigration, Citizenship, Refugees, Border Security, and International Law.

Testimony of Muzaffar Chishti, Director of MPI's Office at New York University Law School, before the House Homeland Security Committee. 

Testimony of Marc R. Rosenblum, Deputy Director, U.S. Immigration Program, before the House Committee on Homeland Security Subcommittee on Oversight and Management Efficiency.

Testimony of Doris Meissner, Director of MPI's U.S. Immigration Policy Program, before the Senate Judiciary Committee's Subcommittee on Immigration and the National Interest regarding the Central American Minors Refugee/Parole Program that began in December 2014.

Given the rapid spread of COVID-19 and its relatively high mortality, filling the gap for coronavirus-specific drugs is urgent.