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

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

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

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.

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.

Illegal immigration is possible in large part because of illegal employment. This report shows the underlying drivers of illegal hiring vary based on the type of employer, the nature of the industry, state of the economy, and a country’s labor market institutions, employment legislation, immigration systems, and even culture.

This book takes stock of the impact of the crisis on immigrant integration in Europe and the United States. It assesses where immigrants have lost ground, using evidence such as levels of funding for educational programs, employment rates, trends toward protectionism, public opinion, and levels of discrimination.

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

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.

Public Policy Institute of California researchers Magnus Lofstrom and Laura Hill discuss their research examining the potential labor market outcomes and other possible economic effects of a legalization program.

Public Policy Institute of California researchers Magnus Lofstrom and Laura Hill discuss their research examining the potential labor market outcomes and other possible economic effects of a legalization program. The discussion was moderated by Doris Meissner, MPI Senior Fellow and Director of the U.S. Immigration Policy Program, with comments from MPI Senior Policy Analyst Randy Capps and Sherrie A. Kossoudji, Associate Professor, School of Social Work, and Adjunct Professor, Department of Economics, University of Michigan.

New research provides the first direct evidence that Zika virus causes severe birth defects, and explains exactly how it does so

“I lifted up my T-shirt to check on what I thought had just been a small heat rash,” writes BuzzFeed correspondent Ali Watkins. “It had shown up along the right of my back, extending out from a handful of mosquito bites I had picked up… it had seemed relatively tame [but] now, it was inching across the front of my stomach and down my legs... Meanwhile, my right eye was inflamed and bright red, almost akin to a busted blood vessel.”

Watkins is describing the symptoms of a Zika virus infection that she contracted on a recent trip to Mexico. For many people, infection with this mosquito-borne virus causes an illness with symptoms just like those experienced by Watkins: fever, skin rash, joint pain and conjunctivitis. For others, these symptoms are so mild that they go completely unnoticed.

Related: Zika virus spreads across Americas - in pictures

Related: Zika forest: birthplace of virus that has spread fear across the world

New research shows that a genetic mutation associated with schizophrenia alters the process of cellular differentiation, disturbing the balance of neurons and glia in the brain

Stem cells obtained from patients with schizophrenia carry a genetic mutation that alters the ratio of the different type of nerve cells they produce, according to a new study by researchers in Japan. The findings, published today in the journal Translational Psychiatry, suggest that abnormal neural differentiation may contribute to the disease, such that fewer neurons and more non-neuronal cells are generated during the earliest stages of brain development.

Schizophrenia is a debilitating mental illness that affects about 1 in 100 people. It is known to be highly heritable, but is genetically complex: so far, researchers have identified over 100 rare genetic variations and dozens of mutations associated with increased risk of developing the disease.

Related: Brain’s immune cells hyperactive in schizophrenia

Related: Turning urine into brain cells | Mo Costandi

New research shows that we can train our brains to become memory champions

To many of us, having to memorize a long list of items feels like a chore. But for others, it is more like a sport. Every year, hundreds of these ‘memory athletes’ compete with one another in the World Memory Championships, memorising hundreds of words, numbers, or other pieces of information within minutes. The current world champion is Alex Mullen, who beat his competitors by memorizing a string of more than 550 digits in under 5 minutes.

You may think that such prodigious mental feats are linked to having an unusual brain, or to being extraordinarily clever. But they are not. New research published in the journal Neuron shows that you, too, can be a super memorizer with just six weeks of intensive mnemonic training, and also reveals the long-lasting changes to brain structure and function that occur as a result of such training.

Related: The Homer Simpson effect: forgetting to remember

Related: A neural pathway that erases memories

....GOING TO DO WHEN THEY BELIEVE THEY APPLY TO THEM BUT THEY HAVEN'T BEEN HOLY SPIRIT BAPTIZED? TODAY'S CHRISTIANS HAVEN'T BEEN "QUICKENED BACK TO LIFE" (EPHESIANS 2:1)  BY HIS "POWER THAT CAME UPON THEM" (ACTS 1:8) WITH HOLY SPIRIT BAPTISM (ACTS 1:5) AS THEY WERE "BORN AGAIN OF THE SPIRIT" (JOHN 3:5-7) FROM THEIR "DEAD SPIRITS" (ROMANS 5:12-14) AND WERE "RESURRECTED" (I COR 15) FROM THEIR GRAVES" (EZEKIEL 37:12-14). WHAT ARE THESE "DEAD SPIRITS" GOING TO DO? 

The U.S. Food and Drug Administration issued the first emergency use authorization for a new kind of coronavirus test this week.

This report assesses the labor market outcomes of new immigrants in the Czech Republic, focusing on trends according to year of arrival, country of origin, gender, level of education, and sector of employment. The analysis suggests that the challenge of reducing obstacles to immigrant workers’ progression into more skilled employment are worth significant policy attention.

This report presents an overview of Czech integration policies, with a special focus on economic integration. It focuses on policies designed to support migrants’ incorporation in the Czech labor market, and assesses the extent to which these policies facilitate migrants’ upward mobility into more skilled work.

Ahead of National Citizenship Day, this commentary examines how regulations for the implementation of the federal Workforce Innovation and Opportunity Act (WIOA) at state and local levels could jeopardize citizenship preparation services for millions of immigrants across the United States.

Letter submitted by Marc R. Rosenblum, Deputy Director, U.S. Immigration Program, at the request of the Minority Staff of the House Oversight and Government Reform Committee for the February 25, 2015 joint subcommittee hearing reviewing apprehension, detention, and release policies regarding unauthorized immigrants.

Testimony of Andrew Selee, President of MPI, before the Senate Judiciary Committee's Subcommittee on Border Security and Immigration on December 12, 2018 regarding the intersections of transnational crime, immigration, and border security.

(May 1, 2020) On April 24, 2020, the Russian government portal for legal information published the text of the newly adopted Law on Amending the Law on Citizenship. (Federal Law No. 134-FZ of April 24, 2020, Concerning the Simplification of the Procedure for Acquisition of Russian Citizenship.) The new law, which will enter into force […]

(May 1, 2020) On April 24, 2020, Singapore’s chief justice announced an extension to June 1, 2020, of the period during which the courts of Singapore would hear only essential and urgent matters in order to slow local transmission of COVID-19. On the same day, the Supreme Court, state courts, and family justice courts each […]

(May 5, 2020) On April 14, 2020, the Tribunal Judiciaire (Trial Court) of Nanterre ordered the French subsidiary of Amazon to limit the activities of its warehouses to processing only orders for items that were essential in coping with the COVID-19 pandemic. Essential items were defined as food, hygiene, and medical products. The court gave […]

Ravi Zacharias (date: 5/10/2020 - Rank: 6)

Producer Karim Morani's daughter Zoa Morani donated her blood for plasmatherapy trials for COVID-19 treatment at Mumbai's Nair hospital today.

This Indian life by Shoba Narayan: Learning life lessons at the local bazaar  Hindustan Times

Joya Kazi’s work on Mindy Kaling’s ‘Never Have I Ever’ helps blend Indian and American cultures  indica News

MercyOne babies receive handmade 'Star Wars' hats to celebrate May 4  Globe Gazette

After Vizag gas leak, Centre issues guidelines for restarting industries post-coronavirus lockdown  khabrisalaGovt issues new guidelines for restarting industries after lockdown  LivemintConsider Week 1 As Trial: Government On Indus...

Realme Narzo 10 confirmed to feature MediaTek Helio G80 gaming processor  Hindustan TimesRealme Narzo 10 officially confirmed to pack Helio G80 SoC - GSMArena.com news  GSMArena.comRealme Narzo 10, Realme Narzo 10A Launch on May 11:...

1. Ajit Doval showers praise on Kashmir forces for Riyaz Naikoo Op, then stern advice  Hindustan Times
2. Fearing retaliatory strike by India after Handwara terror attack, Pakistan increases aerial exercise  Times Now
3. Why Pakistan’s proxy war will now intensify  The Tribune India
4. Ajit Doval dissects Imran Khan’s terror moves in Kashmir, preps India’s counter  Hindustan Times
5. Indian Army retaliates to Pakistan`s ceasefire violation along LoC in Jammu and Kashmir`s Poonch  Zee News
6. View Full coverage on Google News

Two OMer's plan a trip out to eastern Turkey to share the gospel with the lost, as their plans keep changing along the way.

An OM worker in Russia finds opportunities to share Christ's love with members of the Romani ethnic group.

Forty new students registered for OM Philippines-Cebu’s Alternative Learning System (ALS) programme in June, and by faith, their financial needs have been met.

Marie Reyes from Australia led the Out of the Comfort Zone Cebu team, and shares lessons she learnt during the two-week outreach.

OM Greece's involvement with refugees is always evolving. This summer the team is able to work in more camps and connect with more people.

God is working to transform lives in Mozambique through the efforts of the local OM team.

Limardes Domingo, an OM worker in Mecula, Mozambique, has seen church growth over two years through God's faithful answers to prayer.

During their visits in Serbia, Moldova and Montenegro the two MDT Love Europe teams had many experiences, as well as opportunities to share God’s love.

The OM short-term team seek God’s will for their ministry after their move to the outskirts of Zurich. Recent encounters have encouraged and surprised them.

Träff International, OM Switzerland’s newest project, offers hospitality to people in the community every Wednesday morning.

some testimonies from Aussies who attended the 2010 OCZ and outreaches

Penang, Malaysia :: A team from Logos Hope connect with children at a drop-in centre.

Currently 100 people from 15 nations are expected at OM Malaysia’s annual missions conference at Golden Sands in Port Dickson, Malaysia, from 14-18 July 2012.

Board members from OM Malaysia joined 110 participants from 18 nations in the 10-year celebration of the Out of the Comfort Zone conference this year.

In June, 162 people from 28 countries participate in Out of the Comfort Zone Asia 2014, followed by outreaches to 12 countries.

A recap of OM's OCZ conference, why it's worth attending and what participants learned this year.