ca Shopping Cart Abandonment Rates - What are yours? By forums.digitalpoint.com Published On :: Sun, 10 May 2020 00:51:05 +0000 Full Article
ca What's the best wording for "In Stock" using a shopping cart? By forums.digitalpoint.com Published On :: Sun, 10 May 2020 00:51:23 +0000 Full Article
ca Where can I transfer .com domains at a good price? By forums.digitalpoint.com Published On :: Sun, 10 May 2020 08:39:32 +0000 Full Article
ca Meet the Ohio health expert who has a fan club — and Republicans trying to stop her By news.yahoo.com Published On :: Sat, 09 May 2020 05:04:00 -0400 Some Buckeyes are not comfortable being told by a "woman in power" to quarantine, one expert said. Full Article
ca Ahmaud Arbery is dead because Americans think black men are criminals By news.yahoo.com Published On :: Fri, 08 May 2020 10:07:46 -0400 Whenever Americans see videos of police brutality against black men and women, the first thing they do is assume they deserved their executionWhat skin color are the bad guys in America’s fantasies of vigilantism? When the proverbial “fellas” get together to drink beers and talk about their newest guns and who they’d take down, what race are the “criminals” in the theater of their minds?When Greg McMichael and his son, Travis, got the call from their neighbor that a “burglar” was running through their Brunswick, Georgia neighborhood that chilly February day, what color man do you think they imagined as they locked, loaded, and embarked on their “mission”?Ahmaud Arbery is dead today because when Americans dream of vigilante justice, black men are the villains of their imaginations.We as a nation are so comfortable with this baseline bigotry that our first assumption whenever we see videos of police brutality against or shootings of black men and women, the first thing we do is assume that the victims must have done something wrong to earn their own public execution.This assumption is both a function of white America having a completely different experience with police officers than black America as well as the hundreds of years of vilifying blackness in media and American culture.I will never forget the biggest and most uproarious applause during the theater debut of the lackluster 2007 vigilante film, Brave One, came when the protagonist Jodi Foster got her first vigilante kills of the movie – two threatening and scary black men. That theater filled with men the same age range as Greg and Travis McMichael erupted as if at that moment, all that they had ever imagined had been fulfilled on the big screen. Needless to say, I left that theater before the credits rolled.Across the country, our political leaders hold these same bigoted beliefs which inevitably lead to policies that directly assume criminality based on skin color.During his tenure as mayor of New York City, billionaire Michael Bloomberg made it explicitly clear why it was that he sent police officers into black and brown communities to “throw them” up against the wall. In his 2015 Aspen Institute speech he stated:“People say, ‘Oh my God, you are arresting kids for marijuana who are all minorities.’ Yes, that’s true. Why? Because we put all the cops in the minority neighborhoods. Yes, that’s true. Why’d we do it? Because that’s where all the crime is. And the way you should get the guns out of the kids’ hands is throw them against the wall and frisk them.”And it is for this reason that I do not distinguish between the violence committed by American citizens acting as vigilantes and the violence committed by so-called officers of the law when, in both cases, the working assumption and driving force behind that violence is the deeply bigoted and firmly American association between blackness and criminality.For Ahmaud, that association not only led to his brutal killing, but it also initially meant his killer not being arrested. It took more than two months for the father and son duo to be arrested. When explaining why they were not charged immediately the district attorney, George Barnhill, immediately stated that the victim, Ahmaud Arbery, was, in fact, the “criminal suspect”.“It appears that [Greg and Travis McMichael’s] intent was to stop and hold this criminal suspect until law enforcement arrived. Under Georgia Law [sic] this is perfectly legal.”Even after viewing the video and with no evidence beyond Ahmaud’s skin color, the top cop in the institution designed to bring equal justice under the law concluded that Ahmaud was a criminal suspect when he was simply a black man taking a jog.What are black Americans to do when justice is delayed or outright denied because of the assignment of innocence to vigilantes and police officers?What are black Americans to do when the assumption of guilt because of our skin color is as American as the guns they use to kill us?What are we to do when in our neighbors’ dreams and fantasies of cop-and-robber, the skin color of the bad guy matches our own?The very first thing we are going to do is defend ourselves as if our lives depend on it because when Americans fantasize about killing, those fantasies become our living nightmares. * Benjamin Dixon is the host of the Benjamin Dixon show. Full Article
ca Top Republican Lawmaker Disclosed Stock in Chinese Company He Labeled a Nat Sec Threat By news.yahoo.com Published On :: Fri, 08 May 2020 10:25:45 -0400 Representative Michael McCaul, who has harshly criticized China in his position as the ranking member on the House Foreign Affairs Committee, disclosed that his family owns stock in a Chinese tech company he described as a threat to national security.An April 20 periodic transaction report showed that McCaul disclosed a February purchase of between $50,000 and $100,000 in shares of the Chinese firm Tencent Holdings, Politico reported.In November, several months before the shares were purchased, the Texas congressman said that Tencent Holdings is among the "Chinese companies that threaten America’s economic and national security."The tech conglomerate is "heavily involved" in the "social credit system, a dystopian system China has implemented to score its citizens’ behavior," McCaul said at the time, as well as an "integral part" of the Chinese Communist Party’s industrial policies and "one of four national champions for artificial intelligence."McCaul's lawyer, Elliot Berke, said that the shares are not owned personally by McCaul but by his wife, and the decision to invest in Tencent was made by a third party.“Congressman McCaul did not purchase any shares in China’s Tencent Holdings or any other Chinese company,” the attorney said. “Congressman McCaul’s wife has assets she solely owns and a third party manager made the purchase without her direction.”Rachel Walker, a spokeswoman for McCaul, emphasized that the revelation of the Tencent shares “highlights that many Americans unwittingly invest their money in Chinese owned companies."Federal employees are often unaware they own such investments because the federal government’s thrift savings plan program creates portfolios that include Tencent and other Chinese companies, Walker said. McCaul has argued that such retirement investment plans should not invest American dollars in such "shady" Chinese companies, often without the knowledge of the investor."Congressman McCaul has been a fierce critic of the brutal behavior of the Chinese Communist Party and will continue to fight to hold them accountable as the Chair of the China Task Force," Walker said. "This should be a wake-up call to us all that the CCP’s involvement in the U.S. economy is far more reaching than many Americans realize and that we need to change the way we do business with China, including our investments."Tencent owns the Chinese social media platform WeChat, which has more than one billion users and is suspected of monitoring the activities of users both inside and outside of China. Tencent is also associated with Chinese tech firm Huawei, which U.S. officials said can secretly access American cellular phone networks, giving it access to sensitive information.McCaul has taken a leading role in criticizing China's handling of the coronavirus pandemic as well, accusing Beijing of launching perhaps the "worst cover-up in human history."He was tapped on Thursday by House Minority Leader Kevin McCarthy as chairman of the China Task Force, the aim of which is to develop "legislative solutions to address the Chinese Communist Party’s malign global agenda."The task force will "develop new and enduring policy solutions that, among others, enhance our economic strength and create jobs, protect our national security, rethink our supply chains and grow our competitive edge in technology," McCaul said in a statement on his appointment. Full Article
ca South Dakota Governor demands Sioux tribes 'immediately' remove COVID-19 checkpoints because they interfere with traffic By news.yahoo.com Published On :: Sat, 09 May 2020 17:44:40 -0400 South Dakota Governor Kristi Noem sent letters to two Sioux tribes demanding they remove COVID-19 checkpoints because they interfere with traffic. Full Article
ca China reports first coronavirus case in Wuhan since April 3 among 14 new infections By news.yahoo.com Published On :: Sat, 09 May 2020 21:46:27 -0400 China's National Health Commission reported 14 new confirmed coronavirus cases on May 9, the highest number since April 28, including the first for more than a month in the city of Wuhan where the outbreak was first detected late last year. While China had officially designated all areas of the country as low-risk last Thursday, the new cases according to data published on Sunday represent a jump from the single case reported for the day before. The new Wuhan case, the first reported in the epicentre of China's outbreak since April 3, was previously asymptomatic, according to the health commission. Full Article
ca Canada PM 'worried' about situation in Montreal By news.yahoo.com Published On :: Sat, 09 May 2020 16:59:11 -0400 Prime Minister Justin Trudeau called Saturday for caution and expressed concern about loosening lockdown measures in Montreal, the epicenter of Canada's coronavirus outbreak. While several Canadian provinces, including Quebec, are preparing reopening measures and a gradual revival of their economies, Trudeau stressed prudence and said that the country is not yet out of danger. Quebec is the worst-hit province in Canada, with more than half of both the country's 67,000 cases of coronavirus and 4,700 deaths. Full Article
ca A photographer spent two weeks flying around in helicopters to capture the parked planes at US airports during the pandemic — see his eerie and beautiful work By news.yahoo.com Published On :: Fri, 08 May 2020 15:01:07 -0400 Travel blogger and photographer Andy Luten drove 4,200 miles across six states to see the grounded jets, detailing the shocking state of aviation. Full Article
ca Lockdown Mutiny Brews in California After Guv Blames Nail Salon for Spreading COVID-19 By news.yahoo.com Published On :: Sat, 09 May 2020 15:00:07 -0400 On Thursday, the Professional Beauty Federation of California published a press release to the “Hot Topics” section of their website. It was titled: “Time to Sue Governor Newsom.” The release came in response to Gov. Gavin Newsom’s announcement that the following morning, California would officially enter “Phase Two” of the “Safer at Home” order. Select businesses, from florists to clothing retailers to toy stores, would be able to resume operations in a limited capacity. But absent from the list of acceptable businesses: beauty salons. Newsom placed businesses like nail salons and barbershops in “Phase Three”—a stage he believes to be “months, not weeks” away. “This whole thing spread in the state of California—the first community spread—was in a nail salon,” Newsom said in a press conference last week, without providing details about the date or location of the case. “Many of the practices that you would otherwise expect of a modification were already in play in many of these salons, with people that had procedure masks on, were using gloves, and were advancing higher levels of sanitation.”The news has thrust nail salons onto the frontline of a growing coronavirus revolt in California, a battle being waged in many more American cities, like Dallas, where hairdresser Shelley Luther became a star of the anti-lockdown movement when she opted to go to jail rather than comply with an order to close her hair salon. Anti-Lockdown Protesters Are Now Facing Down Cops Outside of BarsOn Monday morning, the Professional Beauty Federation of California will file a lawsuit in federal court demanding a regulated reopening process of their salons. “We were 100 percent behind the lockdown, so that we would not overwhelm our hospitals,” the group’s legal counsel Fred Jones said in an interview with The Daily Beast. “However, after two months of the lockdown, in which, by Gov. Newsom’s own admission, we have succeeded—we have checked the mark, we have flattened the curve—we were anticipating that the governor would allow for gradual reopenings of our beauty salons under strict new guidelines.”Their argument, Jones said, hinges on the fact that, without regulated reopening, stylists will be forced underground to meet financial ends, resulting in a potentially more dangerous risk.“A lot of our stylists are on the brink of starvation in order to make their leases and make ends meet,” Jones said. “So you have a volatile combination of desperate clients and desperate stylists. We know that will lead to thousands of our stylists going underground and moving kitchen to kitchen and house to house. That’s reality. Nobody can argue that. So the real question is: how do you stop that from happening if you’re the governor? You can’t.”He suggested a gradual and controlled reopening would be safer than “stylists going house to house and spreading more than beauty.”Unmasked Protesters Storm Huntington Beach After California Governor’s ClosureSome salons statewide have already opened, defying the statewide order, like an Orange County nail spa owner who has vowed to stay open despite being handed a citation by local police, who ordered her to appear in court in July. “I have to do what I have to do. I’m fighting to provide for my children and myself and my family,” another salon owner, Breann Curtis, of The Clip Cage barbershop in Auburn, California, told Fox40 about her decision to reopen. “It’s very hard. I’m pregnant. I have children.”“Just going into debt every single day,” added Tisha Fernhoff, who owns The Beauty Bar Salon in the same Auburn shopping center. “How much longer am I supposed to just go down the rabbit hole before I just throw in the towel and go back to work?”According to Jones, the California State Board of Barbering and Cosmetology—which issues all 623,442 beauty licenses in the state—has already drafted a protocol for how salons could reopen under the current conditions. He claimed Newsom had blocked the plan from distribution, to avoid mixed messaging. (Newsom’s office didn’t respond to a request for comment and a spokesperson for the Board of Barbering and Cosmetology said their draft protocols “haven't been published because they are not finished.”)“We want him to release the plan so that our professionals can start stocking up,” Jones said. “We know we’ll need masks. Will shields be required for these services? They probably will.”If such a plan was to go into effect, Jones said, salons would use personal protective equipment widely. They would stagger appointments to avoid crowded waiting rooms, spread out work stations and shift schedules, implement a touchless pay system, and remove anything in the waiting rooms that could carry contagion. “So, sorry no more magazines and newspapers for our clientele,” Jones said. But the Centers for Disease Control and Prevention (CDC) recommends maintaining a distance of six feet from other people—a practice that would be all but impossible in salon settings. Dr. Birx Says What Trump Would Not About ProtestersThere are 53,694 licensed beauty salons in California, representing 313,734 stylists or cosmetologists, 34,093 barbers, 90,392 estheticians, 1,679 electrologists, and 129,802 manicurists, according to the State Board of Barbering and Cosmetology. All of these workers, Jones said, have to complete between 350 and 1600 hours of formal education before acquiring their license, including training in sanitization. Jones emphasized that the lawsuit stemmed from financial desperation, a sentiment shared across the country. The Labor Department announced Friday that the economy lost over 20.5 million jobs in April alone, putting the national unemployment rate at its highest since the Great Depression: 14.7 percent. But the devastation has hit the beauty sector differently than many industries. Over 80 percent of salon workers are independent contractors, meaning each stylist represents their own business. By extension, many salon owners are basically landlords, “whose income relies on those booth owners,” Jones said. As a result, most salon workers qualify for unemployment benefits under the Coronavirus Aid, Relief and Economic Security Act, signed by Trump in March—although the program is riddled with loopholes, has frequently run out of money, and may not cover their entire income, which heavily relies on tips. It is salon owners who stand to gain the most from the lawsuit. “Freelance workers do benefit on unemployment benefits,” Jones said. “But most of those Paycheck Protection Program reimbursements are based on your payments. If you’re a salon owner, you don’t have a payroll. Those stylists are their own proprietors.”On Friday, Senators Bernie Sanders (I-VT), Ed Markey (D-MA), and Kamala Harris (D-CA) introduced legislation to give a majority of Americans $2,000 a month throughout the pandemic. Asked whether the bill could provide financial relief to salon workers, while allowing them to maintain social distancing, Jones seemed doubtful that it would pass. “It’s the proverbial ‘check is in the mail’ promise,” he said. “When you’re dealing with true economic devastation, let me tell you, most of our licensees will not be banking on a divided Congress and a White House that is also divided. While Washington fiddles, our stylists are burning.” Read more at The Daily Beast.Get our top stories in your inbox every day. Sign up now!Daily Beast Membership: Beast Inside goes deeper on the stories that matter to you. Learn more. Full Article
ca Elon Musk says Tesla will 'immediately' leave California after coronavirus shutdowns forced the company to close its main car factory By news.yahoo.com Published On :: Sat, 09 May 2020 13:34:00 -0400 In a tweet Saturday morning, Tesla's chief executive said it would file a lawsuit against county officials over not being able to run its factory. Full Article
ca Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 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. Full Article
ca Affinity maturation, humanization, and co-crystallization of a rabbit anti-human ROR2 monoclonal antibody for therapeutic applications [Immunology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms. Full Article
ca Development of a novel {beta}-1,6-glucan-specific detection system using functionally-modified recombinant endo-{beta}-1,6-glucanase [Methods and Resources] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections. Full Article
ca Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 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. Full Article
ca An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1 [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 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. Full Article
ca Glycation-mediated inter-protein cross-linking is promoted by chaperone-client complexes of {alpha}-crystallin: Implications for lens aging and presbyopia [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 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. Full Article
ca Catabolic degradation of endothelial VEGFA via autophagy [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
ca Structural basis of substrate recognition and catalysis by fucosyltransferase 8 [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
ca Endorepellin evokes an angiostatic stress signaling cascade in endothelial cells [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
ca Re: Clinical features of covid-19 By feeds.bmj.com Published On :: Saturday, May 9, 2020 - 09:36 Full Article
ca Re: Covid-19: how to use your time when clinical placements are postponed - Wellbeing perspective By feeds.bmj.com Published On :: Saturday, May 9, 2020 - 13:41 Full Article
ca Re: Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis By feeds.bmj.com Published On :: Saturday, May 9, 2020 - 18:01 Full Article
ca Call for a review of services for people with neurological disorders By feeds.bmj.com Published On :: Tuesday, August 11, 2015 - 15:35 Full Article
ca Doctors can withdraw feeding from patient in minimally conscious state, judge rules By feeds.bmj.com Published On :: Friday, November 20, 2015 - 13:16 Full Article
ca Environment may play significant role in multiple sclerosis By feeds.bmj.com Published On :: Monday, March 21, 2016 - 06:30 Full Article
ca Cancer Drugs Fund requires further reform By feeds.bmj.com Published On :: Tuesday, September 27, 2016 - 11:26 Full Article
ca Pay-to-Go Schemes and Other Noncoercive Return Programs: Is Scale Possible? By www.migrationpolicy.org Published On :: Fri, 01 Apr 2011 00:00:00 -0400 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. Full Article
ca New Streams: Black African Migration to the United States By www.migrationpolicy.org Published On :: Wed, 01 Jun 2011 00:00:00 -0400 This report explores the migration patterns and demographics of Black African immigrants in the United States, examining their admission channels, human-capital characteristics, and labor market performance. The authors also provide an analysis of these immigrants' integration prospects. Full Article
ca Mexican and Central American Immigrants in the United States By www.migrationpolicy.org Published On :: Wed, 01 Jun 2011 00:00:00 -0400 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. Full Article
ca A shell in the cap By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:22:10 -0500 Cowrie shells are a group of sea snails that range in size from small to large. These shells are famous the world over, with the most popular species of this shell known as the money cowrie or Monetaria moneta. The money cowrie are double-sided,... Full Article
ca Cavalier get top rating in Concacaf - Players under-21 accounting for 58.1 per cent of the team’s minutes over the course of the season By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:24:49 -0500 Cavalier’s technical director, Rudolph Speid, says the recent positive ranking by CIES (International Centre for Sports Studies) Football Observatory, a research group based in Switzerland, is a reflection of the work the club is doing in trying to... Full Article
ca #JamaicaTogether | Portia Simpson Miller By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:16:51 -0500 As daunting as this COVID-19 pandemic has proven to be, and as devastating as its impact is on people both here at home and around the world, we must stand together, united. We must all act with purpose, resolve, love and compassion because when we... Full Article
ca Daddy, when are you coming home? - Stranded Jamaican cruise ship worker dreads Mother’s Day away from family By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:26:51 -0500 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... Full Article
ca Queen of foster care - Supermom Mama Sweetie opens big heart to more than 40 children By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:05:40 -0500 To say Judith-Miranda Townsend has a special love for children would not even begin to capture the essence of the Westmoreland supermom. Affectionately called ‘Mama Sweetie’ by foster children and members of the Holly Hill community in Darliston,... Full Article
ca Costly no-shows - Cancellation of major entertainment events could have $10b impact By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:27:12 -0500 Losses within the entertainment industry are already estimated to be in the billions as the sector continues to reel from the impacts of COVID-19. Major events like Reggae Sumfest, which has already been cancelled this year, had an estimated... Full Article
ca CRIPPLED - Several St Catherine businesses hobbling as lockdown jitters linger By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:28:03 -0500 At least 10 stores inside the Portmore Mall have fallen casualty to the economic chokehold brought on by the COVID-19 pandemic, with several others struggling to stay afloat as St Catherine businesses grapple with revenue losses. And with a 14-day... Full Article
ca Changing Demography and Circumstances for Young Black Children in African and Caribbean Immigrant Families By www.migrationpolicy.org Published On :: Sun, 01 Apr 2012 00:00:00 -0400 This report finds that the 813,000 U.S. children under the age of 10 who have Black immigrant parents from Africa or the Caribbean generally fall in the middle of multiple well-being indicators, faring less well than Asian and white children but better than their native-born Black and Hispanic peers. Citizenship status, English proficiency, parental characteristics, poverty, housing, and access to social supports are examined. Full Article
ca A Demographic Profile of Black Caribbean Immigrants in the United States By www.migrationpolicy.org Published On :: Sun, 01 Apr 2012 00:00:00 -0400 Immigration from the Caribbean to the United States is a relatively recent phenomenon, beginning largely after 1965. This report provides a demographic profile of the 1.7 million Caribbean immigrants in the United States: their geographic settlement, education and workforce characteristics, earnings, modes of entry, and more. Full Article
ca Diverse Streams: African Migration to the United States By www.migrationpolicy.org Published On :: Sun, 01 Apr 2012 00:00:00 -0400 African immigrants generally fare well on integration indicators, with college completion rates that greatly exceed those for most other immigrant groups and U.S. natives, this report finds. The United States, Canada, and Australia disproportionally attract better-educated African migrants then do the United Kingdom, France, and other European countries. Full Article
ca Young Children of Black Immigrants in America: Changing Flows, Changing Faces By www.migrationpolicy.org Published On :: Fri, 14 Dec 2012 00:00:00 -0500 The event discussion, which touched on the intersection of race and immigration, focused on the demographics of Black immigrants (both African and Caribbean) in the United States and their children, their educational success, and the implications of the recently released volume’s findings for research and public policy. Full Article
ca Young Children of Black Immigrants in America: Changing Flows, Changing Faces By www.migrationpolicy.org Published On :: Fri, 14 Dec 2012 15:30:00 -0500 Book release event for MPI's volume on the Children of Black Immigrants, covering topics of education, health, and demographics, with U.S. Department of Health and Human Services Deputy Assistant Secretary for Human Services Policy Ajay Chaudry; Gerald D. Jaynes, Yale University Departments of Economics and African-American Studies; chapter authors Dylan Patricia Conger and Kevin Thomas; and volume editors MPI's Randy Capps and Michael Fix. Full Article
ca Critical Immigration, Health, and Education Policies Affecting Young Children of Immigrants By www.migrationpolicy.org Published On :: Thu, 17 Jan 2013 00:00:00 -0500 MPI’s National Center on Immigrant Integration Policy convened a major public policy research symposium focused on young children of immigrants in the U.S. Full Article
ca Sub-Saharan African Immigrants in the United States By www.migrationpolicy.org Published On :: Wed, 29 Oct 2014 17:53:03 -0400 From 1980 to 2013, the sub-Saharan African immigrant population in the United States increased from 130,000 to 1.5 million, roughly doubling each decade between 1980 and 2010. This profile provides up-to-date demographic information for sub-Saharan immigrants including location, educational attainment, workforce participation, and much more. Full Article
ca GAP wants to delay capital projects at local airports By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:22:48 -0500 The operator Jamaica’s two largest airports wants to scrap or delay non-essential capital projects. It forms part of a wider halt of capital projects by the Grupo Aeroportuario del Pacífico – which translate to Pacific Airport Group, or GAP –... Full Article
ca Virus crushes car rentals By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:25:17 -0500 Car-rental companies in Jamaica are facing a serious crush, with at least one medium player looking to shut down operations, and others, big and small, saying that they are barely holding on. The collapse in the vacation market and travel... Full Article
ca Reopenings result in new COVID cases in S. Korea, virus fears in Italy By jamaica-gleaner.com Published On :: Sat, 09 May 2020 15:32:26 -0500 (AP): South Korea’s capital, Seoul, has closed down more than 2,000 bars and other nightspots because of a new cluster of COVID-19 infections; Germany scrambled to contain fresh outbreaks at slaughterhouses; and... Full Article
ca Jamaica two cases away from 500 COVID infections By jamaica-gleaner.com Published On :: Sat, 09 May 2020 22:12:56 -0500 Jamaica is now two cases shy of 500 confirmed COVID-19 infections with the confirmation of eight new cases in the past 24 hours. The new infections bring the total number to 498 confirmed COVID-19 cases. In a release a short while... Full Article
ca COVID-19 from a Biblical perspective By jamaica-gleaner.com Published On :: Sun, 10 May 2020 00:20:19 -0500 The common questions that many are asking today in relation to the COVID-19 pandemic are: Why has this befallen us? Why is there so much death and dying from this disease? Where is God in all of this? If God exists, why doesn’t He intervene and... Full Article