SAN DIEGO – Today, the U.S. Environmental Protection Agency (EPA), in coordination with the North American Development Bank (NADB), released a Request for Proposals (RFP) through the Border 2020 Program.

Environmental News FOR IMMEDIATE RELEASE

Environmental News FOR IMMEDIATE RELEASE

Former Mayo manager Stephen Rochford feels the difference between a Dublin side he calls the "greatest in history" and the Mayo, Kerry and Tyrone teams they have beaten on the way to five in a row is the ability to convert scoring opportunities in finals.

Investigators are using additional video footage to reconstruct the February afternoon that Ahmaud Arbery was fatally shot in a quiet southern Georgia neighborhood.

Investigators are using additional video footage to reconstruct the February afternoon that Ahmaud Arbery was fatally shot in a quiet southern Georgia neighborhood.

There was certainly was stress in the air when health and economic consqeuences of COVID-19 bore down on Brooklyn and the rest of America. But as these pressures grew, constructive hearts and minds prevailed at the BKLYN Commons (BKC) shared workspace operation at 495 Flatbush Ave., in the Prospect-Lefferts Gardens area, which creatively and passionately morphed to adapt to the new normal.

Exclusive: 'As well as staggered working hours we need to stagger holidays,' says AA president Edmund King

Unilever is recalling Wall’s Mini Calippo (Orange and Lemon-Lime) multi-packs because they may contain small pieces of metal. The presence of metal makes this product unsafe to eat.

Nearly a month after the Facebook page for The Official Quarantine Cookbook gained thousands of followers, the book is available to buy.

Republicano perdeu seu principal discurso, os bons números econômicos, seis meses antes da eleição. Agora, luta para ser visto como bom gestor da crise.

Electronic Arts Drops Prices on iOS and Android Games

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

Mercedes' Lewis Hamilton has said that holding races without any fans will feel "even worse than a test day".

Hospitals in British Columbia and Ontario are beginning to address major backlogs in surgeries after the COVID-19 pandemic forced thousands of cancellations that could take well over a year to address.

12 November 2014 , Volume 90, Number 6

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

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.

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.

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.

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.

Using a nationally representative U.S. birth-cohort study, this report examines levels of school readiness among young children by race/ethnicity and nativity. The authors identify the contextual factors — such as family circumstances, parenting practices, and enrollment in center-based child care — that encourage early school success.

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.

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.

Recent calls by the Jamaica Manufacturing and Exporters Association, JMEA, for more targeted concessions on raw materials that are processed for re-export sent Jamaica Agricultural Commodities Regulatory Authority, JACRA, back to the drawing board...

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. 

This interdisciplinary volume examines the health, well-being, school readiness, and academic achievement of children in Black immigrant families (most with parents from Africa and the Caribbean)—a population that has had little academic attention even as it represents an increasing share of the U.S. Black child population.

The enactment of President Clinton’s Limited English Proficiency (LEP) Executive Order, issued in 2000, triggered a proliferation of efforts to provide services to individuals who cannot speak, understand, read, or write English fluently. With increased service provision, state and local government agencies have expressed a strong and growing interest in assuring the quality and cost-effectiveness of language access services. This paper attempts to catalog and describe some of those tools and practices.

This interactive language access webinar, one in a series offered by the Migration Policy Institute's National Center on Immigrant Integration Policy, examines how New York and Illinois have broken down some of these barriers to proactively engage LEP communities to obtain workforce services.

This webinar examines how New York and Illinois have proactively engaged Limited English Proficient (LEP) communities to obtain workforce services.

In this webinar, experts discuss barriers immigrant and LEP individuals face in accessing the WIA system, how a revitalized WIA could address these barriers, and the extent to which the current Senate Health, Education, Labor, and Pensions (HELP) Committee's WIA reauthorization proposal addresses these barriers.

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.

This MPI webinar features U.S. Department of Justice (DOJ) officials discussing the department’s efforts to improve communications with Limited English Proficient (LEP) communities in federal and federally-funded programs and activities.

This MPI webinar features U.S. Department of Justice (DOJ) officials discussing the department’s efforts to improve communications with Limited English Proficient (LEP) communities in federal and federally-funded programs and activities.

A webinar on language access contracting for federal, state, and local officials, agency administrators, and community stakeholders concerned with the oversight and implementation of language access provision.

A webinar on language access contracting for federal, state, and local officials, agency administrators, and community stakeholders concerned with the oversight and implementation of language access provision.

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.