Two more businesses operating in Calgary have been shut down by health officials for violating the province's rules regarding COVID-19.

A man is dead after a single-vehicle motorcycle crash in southeast Calgary.

Frank Soo, the first and only player of Asian heritage to represent England's national football team, has been honoured by Google.

Manchester United and Everton have been put on alert by the news that Juventus midfielder Adrien Rabiot is willing to move to the Premier League.

My friend Steve Davee posted this fun project to Instructables. It's a perfect project for shut-in parents and kids to do together.

The main body parts of the bots are keyboard keycaps and Q-tips/cotton swabs. An eccentric weight (pager) motor provides the bouncy movement that makes your vibrobots go.

Dip the swabs in watercolor paints, place the little critter on some paper, and watch your little tabletop Jackson Pollockbot go to town.

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The DML News App offers the best in news reporting.

The post VIDEO: Lindsey Graham puts Obama on notice after Justice Department swipe appeared first on Dennis Michael Lynch.

The following article, California Sheriff Refuses to Arrest People Defying Stay-at-Home Order: “There cannot be a new normal”, was first published on 100PercentFedUp.com.

Riverside, California Sheriff Chad Bianco spoke to the Riverside Board of Supervisors on May 5th to say that he will not enforce the stay-at-home order in California. He tells people who are afraid of contracting the coronavirus that they should stay home if they want to. Bianco continues with the suggestion that any business owner […]

Continue reading: California Sheriff Refuses to Arrest People Defying Stay-at-Home Order: “There cannot be a new normal” ...

The following article, Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going”, was first published on 100PercentFedUp.com.

Ilhan Omar is a lot of things. First, and foremost, she’s deceitful. David Steinberg of PJ Media was one of the first investigative journalists to break the story about the anti-Semitic, freshman lawmaker’s marriage to her immigrant brother while she was still married to her first husband, who she has since divorced after having an […]

Continue reading: Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going” ...

A crowd descended on the Manitoba Legislature Building Saturday afternoon, demanding an end to the COVID-19 quarantine.

8 November 2013

Members Event

Event participants

Professor Shaun Breslin, Associate Fellow, Asia Programme, Chatham House
Professor Jane Duckett, Edward Caird Chair of Politics; Director, Confucius Institute; Director, The Scottish Centre for China Research, University of Glasgow
Professor Christopher Hughes, Head, International Relations Department, LSE
Chair: Rob Gifford, China Editor, The Economist

23 February 2015

Webtraverser posted a photo:

Tyrannosaurus silhouette

ridureyu1 posted a photo:

A thematic interpretation of Scream: Curse of Carnage, using the new NECA Rhino Alien as a stand-in for Grendel's Mother. Like I said, thematic.

Elizabeth Spiers wrote about an incident where Jared Kushner used the memorial of an employee to congratulate himself for success.

South Dakota Governor Kristi Noem sent letters to two Sioux tribes demanding they remove COVID-19 checkpoints because they interfere with traffic.

Nepal protested India's inauguration of a new road to China that passes through territory claimed by Kathmandu on Saturday, with police arresting dozens demonstrating close to India's embassy. Indian defence minister Rajnath Singh on Friday inaugurated via video link the 80-kilometre (50 miles) long road from Ghatiabagarh in northern Uttarakhand state to the Lipu Lekh pass high in the Himalaya. The pass is claimed by Nepal based on an 1816 treaty that defines its western border with India.

The White House has halted talks with Congress over any further coronavirus stimulus package as it waits for more information about how U.S. state reopenings affect the economy, White House top economic adviser Larry Kudlow told reporters on Friday. The Senate and House of Representatives have already passed four major bills to address the novel coronavirus outbreak, including three aimed at stabilizing the economy as most Americans have sheltered in place and unemployment has soared.

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

"Passing along a message from Mother Nature," the National Weather Service in Binghamton, New York, tweeted alongside a photo of a car covered in light snow. "Happy Mother's Day Weekend."

President Trump said Friday he had watched the video of Ahmaud Arbery being shot and found it “very disturbing” and “heartbreaking,” but said he was confident that the Georgia legal system would come down on the side of justice.

Travel blogger and photographer Andy Luten drove 4,200 miles across six states to see the grounded jets, detailing the shocking state of aviation.

Attorney General Bill Barr explained that the FBI did not conduct “a bonafide counterintelligence investigation” in the case that led former Trump national security adviser Michael Flynn to plead guilty to federal investigators in 2017.Barr, speaking in an exclusive interview with CBS News after the Justice Department dropped its case against Flynn on Thursday, said that his review of the case found Bureau investigators laid “a perjury trap” for Flynn in a January 2017 White House interview.“They didn’t warn him, the way that would usually be required by the Department, they bypassed the Justice Department, they bypassed the protocols at the White House, and so forth,” Barr stated. “These were things that persuaded me that there was not a legitimate counterintelligence investigation.”Former FBI director James Comey admitted in a December 2018 interview that he “sent” the agents to interview Flynn, adding that it was “something I probably wouldn’t have done or maybe gotten away with in a more organized administration.”In its Thursday court filing, the Justice Department explained that it was “not persuaded” that Flynn’s interview, which led to his guilty plea for lying to FBI agents Peter Strzok and Joe Pientka, had proper predication and was materially relevant.Comey tweeted his disappointment, following the decision, saying "the DOJ has lost its way."> The DOJ has lost its way. But, career people: please stay because America needs you. The country is hungry for honest, competent leadership.> > -- James Comey (@Comey) May 7, 2020Barr pointed to recently-released information that showed the FBI moved to close its surveillance of Flynn after finding “no derogatory information” about the retired general’s contacts with Russians, only for Strzok to keep the case open, leading to the eventual interview.“They were closing the investigation, in December [2016], they started that process and on January 4, they were closing it. When they heard about the phone call, which the FBI had the transcripts to — there was no question as to what was discussed, the FBI knew exactly what was discussed — and General Flynn, being the former director of the DIA, said to them, ‘you listen to everything, you know what was said,’” Barr explained.“So there’s no mystery about the call, but they initially tried some theories of how could open another investigation, which didn’t fly, and then they found out that they had not technically closed the earlier investigation, and they kept it open for the expressed purpose of trying to catch — lay a perjury trap — for General Flynn,” he added. A different filing released last week showed handwritten notes from an FBI official that questioned if the goal of Flynn’s White House interview was “to get him to lie, so we can prosecute him or get him fired.”Barr also did not comment on whether those that sought to entrap Flynn would face criminal charges, pointing to U.S. Attorney John Durham’s probe into the origins of the Trump-Russia investigation and saying his team was “in the middle” of “looking at the whole pattern of conduct.”“I’m going to wait until all the evidence is [in], and I get their recommendations as to what they found and how serious it is. But, if we were to find wrongdoing, in the sense of any criminal act, obviously we would follow through on that,” Barr said. “But again, just because something may even stink to high heaven, and appear to everyone to be bad, we still have to apply the right standard and be convinced that there is a violation of a criminal statute and that we can prove it beyond a reasonable doubt. The same standard applies to everybody.”

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8–2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168–170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs.

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.

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.

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.

Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80–2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.

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.

Noncoercive, pay-to-go, voluntary, assisted voluntary, and nonforced returns generally can offer paid travel and/or other financial incentive to encourage unauthorized immigrants to cooperate with immigration officials and leave host countries. A look at three key rationales for governments to choose pay-to-go and other returns.

The U.S. refugee protection system, while generous in many respects, has become less robust over the last two decades. The unique and often diverse needs of emerging refugee populations have exposed severe limitations in the standard resettlement approach.This report examines U.S. legal and policy responses to those seeking protection and addresses the barriers, gaps, and opportunities that exist.

Written from, different angles and spaces, the poems below testify to the great force of motherhood, which nurtures, strengthens, and manifests love. Happy Mother’s Day – Ann-Margaret Lim Words My mother loved words. Not necessarily in...

THE LAST two months have been two of the worst in the life of former national netball star Nichala Gibson. She lives in New York City, the epicentre for the COVID-19 virus in the United States. Gibson and her sister suffered, then recovered from...

For drummer Conroy Gordon, the hardest part of being locked away day after day in the narrow confines of a stranded cruise ship is his inability to tell his two daughters when Daddy will be home. For the past month, he has been battling this...

Almost five years ago, lawmakers on a bipartisan committee of Parliament agreed unanimously to amend the law to give the Independent Commission of Investigations (INDECOM) the power to arrest and prosecute cops. That proposed amendment, which was...

This report draws on a six-year longitudinal study of Palm Beach County, FL, examining parenting, child care enrollment, and other factors that encourage early school success. The authors find kindergarten-age children of Black immigrants have significantly higher odds of being ready for school than children of Latina immigrant or Black U.S.-born mothers.

ADVISORY COLUMN: SMALL BUSINESS On Thursday, May 7, the RJR/GLEANER Communications group staged a virtual town hall meeting on Television Jamaica titled “COVID-19...

Uber lost US$2.9 billion in the first quarter as its overseas investments were hammered by the coronavirus pandemic, but the company is looking to its growing food delivery business and aggressive cost-cutting to ease the pain. The ride-hailing...

Mother’s Day is usually a much-anticipated, celebratory day for Trinette Lilly and her siblings. However, this year, they were not looking forward to today because it marks the first anniversary of the brutal slaying of their mother, Antonette...

Monday, May 11, marks 39 years since Robert Nesta Marley OM, died at the University of Miami Hospital in Florida. I was a youngster living on Sunflower Way in Mona Heights, Kingston, on December 3, 1976, when the reggae legend was shot at 56 Hope...

Millie Small, the first Jamaican vocalist in popular music to make the world stop and look at Jamaica as an emerging musical powerhouse, passed away in London on May 5. She was 72 years old. Speaking to Small by telephone from her home in Shepherd’...