eco

Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR [Protein Structure and Folding]

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.




eco

Three distinct glycosylation pathways are involved in the decoration of Lactococcus lactis cell wall glycopolymers [Microbiology]

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.




eco

Development of a novel {beta}-1,6-glucan-specific detection system using functionally-modified recombinant endo-{beta}-1,6-glucanase [Methods and Resources]

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.




eco

Structural basis of substrate recognition and catalysis by fucosyltransferase 8 [Protein Structure and Folding]

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.




eco

Re: Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis




eco

Eight Policies to Boost the Economic Contribution of Employment-Based Immigration

Drawing on experiences from Asia, Europe, North America, and the Pacific region, this report presents eight strategies that represent best practices developed by immigrant-receiving countries to increase the economic contributions of immigration.




eco

The Economic Integration of Immigrants in the United States: Long- and Short-Term Perspectives

The United States has historically offered unparalleled economic opportunity to successive generations of immigrants and their children, poised to play an increasing role in the U.S. economy. But the lasting impact of job loss and slower growth over the next decade will translate into fewer opportunities for workers—and immigrants may prove the most vulnerable.




eco

Big blow for former Sunshine Girl - Registered Nurse Nichala Gibson recovered from COVID-19 but her father was not so lucky

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




eco

Five-year INDECOM Act inertia - Williams, Golding still want prosecutorial powers for commission; DPP, Chuck, cops not sold on idea

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




eco

Yaneek Page | It will be years, not months, for COVID-19 business recovery

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




eco

Migration of Health Workers: The WHO Code of Practice and the Global Economic Crisis

This edited volume from the World Health Organization (WHO), which includes chapters written by MPI researchers, examines country-level responses to the international movement of health-care workers, both before and after adoption of the WHO’s Global Code of Practice on the International Recruitment of Health Personnel.




eco

The Impact of Immigrants in Recession and Economic Expansion

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.




eco

Immigrants: Contributors to the Economy or Competitors for American Jobs?

Briefing and discussion of the release of the latest paper by MPI's Labor Markets Initiative: The Impact of Immigrants in Recession and Economic Expansion.




eco

Immigrants: Contributors to the Economy or Competitors for American Jobs?

Briefing and discussion of the release of the latest paper by MPI's Labor Markets Initiative. Speakers are report author Giovanni Peri, UC Davis Professor of Economics; Ross Eisenbrey, Vice President, Economic Policy Institute; and Demetrios G. Papademetriou, MPI President.




eco

Does Low-Skilled Immigration Hurt the U.S. Economy? Assessing the Evidence

In a report by MPI's Labor Markets Initiative, noted economist and Georgetown University Public Policy Institute Professor Harry J. Holzer examines the economic reasoning and research on these questions and looks at the policy options that shape the impact of less-skilled immigration on the economy. The discussion is on what policy reform would best serve native-born American workers, consumers, and employers, as well as the overall U.S. economy.




eco

Immigrants in a Changing Labor Market: Responding to Economic Needs

This volume, which brings together research by leading economists and labor market specialists, examines the role immigrants play in the U.S. workforce, how they fare in good and bad economic times, and the effects they have on native-born workers and the labor sectors in which they are engaged. The book traces the powerful economic forces at play in today’s globalized world and includes policy prescriptions for making the American immigration system more responsive to labor market needs.




eco

Immigration and U.S. Economic Competitiveness: A View from the Midwest

At this release event in Washington, DC, co-sponsored by MPI, the Chicago Council on Global Affairs, and ImmigrationWorks USA, the Chicago Council's independent task force on immigration released its report, U.S. Economic Competitiveness at Risk: A Midwest Call to Action on Immigration Reform.




eco

How to become a super memorizer – and what it does to your brain

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

Continue reading...




eco

Integration Challenges and Opportunities in the Economic Development and Refugee Resettlement Arenas

Part of a series exploring recommendations likely to be addressed by the new National Integration Plan, this webinar, with perspectives from MPI, the WE Global Network, and Lutheran Immigrant and Refugee Services, examines the role of economic development initiatives and refugee resettlement programs/infrastructure in immigrant integration. 




eco

Integration Challenges and Opportunities in the Economic Development and Refugee Resettlement Arenas

This webinar, with perspectives from MPI, the WE Global Network, and Lutheran Immigrant and Refugee Service, examines the role of economic development initiatives and refugee resettlement programs/infrastructure in immigrant integration.




eco

As New Brunswick enters new recovery phase, here's what you need to know

New Brunswick has entered the next COVID-19 recovery phase, triggering a new round of loosened restrictions and reopening a large swathe of the economy, Premier Blaine Higgs announced Friday.



  • News/Canada/New Brunswick

eco

Filmfare recommends: Bollywood films revolving around journalism – Filmfare

Filmfare recommends: Bollywood films revolving around journalism  Filmfare



  • IMC News Feed

eco

China reports first coronavirus case in Wuhan since April 3 – Economic Times

  1. China reports first coronavirus case in Wuhan since April 3  Economic Times
  2. China admits coronavirus exposed ‘shortcomings’ in healthcare system  Hindustan Times
  3. "Outbreak Big Test That Revealed China's Shortcomings": Top Officer  NDTV
  4. China reports 14 new coronavirus cases, high-risk area resurfaces  Zee News
  5. 34 new Covid-19 cases reported in China, first in Wuhan in more than a month  The Newsopedia
  6. View Full coverage on Google News



  • IMC News Feed

eco

Record low temperatures for Windsor and much of Ontario as Arctic front moves through

An Arctic cold air mass brought record low temperatures in Windsor and other cities around the province last night



  • News/Canada/Windsor

eco

Four baptisms becomes five

After watching others be baptised, an Uzbek lady who had recently repented in the church expressed her desire to follow the others’ example.




eco

Holiday Bible class becomes community event

The OM Philippines-Cebu team, in partnership with the local church, touches the lives of young and old through a five-day Bible class.




eco

OM starts reconstruction in three locations

As local markets begin to re-establish themselves, the OM Philippines crisis response team takes steps towards reconstruction in Tacloban, Bohol and Northern Cebu.




eco

Journey towards recovery

OM Philippines-Cebu conducts critical incident stress debriefing training with partner organisations and churches in Cebu City, Northern Cebu and Bohol Island.




eco

Recognising refugees as people

A long-term worker overseeing refugee relief work on Lesbos describes the people he’s met on the island, the chances he’s had to share his faith and how God has shown up during the crisis.






eco

Fin24.com | OPINION | Transport SOEs: A crucial link in SA's economic recovery

Ofentse Mokwena discusses what's needed for opening transport markets and unbundling transport SOEs.




eco

Why the SNP's pro-EU allies are becoming increasingly frustrated by the party's friendly fire attacks

THE Treasury has bombarded us all week with facts, figures and forecasts making the case for the UK to remain in the European Union. Its big report, on Monday, warned Brexit would tip the country into a year-long recession, resulting in up to 820,000 job losses within two years.




eco

Would Brexit, against the wishes of most Scots, trigger a second independence referendum?

THE warning is becoming louder. It was raised by the Leave team during Thursday's TV debate and, on the same day, by the Chancellor, George Osborne, and two former prime minsters, Sir John Major and Tony Blair. Brexit, they said, posed a serious threat to the Union.




eco

Building a bridge to reconciliation

Teens attending TeenStreet Europe in July will raise money for a project to bring reconciliation to the ethnically divided youth of Mostar, Bosnia and Herzegovina.




eco

Hearts owner Ann Budge hits out at "shameful" decision to scrap reconstruction plans

Hearts owner Ann Budge has described the decision by Ladbrokes Premiership clubs to scrap league reconstruction as "shameful" and vowed the Tynecastle club will "formally challenge" any decision to end the top flight prematurely if they are relegated.




eco

Altoona student recognized at Penn State Undergraduate Exhibition

Andrea Regalbuto was awarded second place in the oral presentation category for Arts and Humanities at the Penn State Undergraduate Exhibition, held virtually April 15-17.




eco

Honda Dio beats Suzuki Access 125 to become India’s second highest-selling scooter, Activa remains the king!

The BS6 Honda Dio is priced at Rs 59,990 for the standard model and Rs 63,340 for the deluxe variant (both prices mentioned, ex-showroom). 




eco

Now buy a second-hand bike, scooter and get it delivered to your doorstep amid lockdown, here’s how!

Once the two-wheeler arrives at the doorstep of the customer, the customer can take a test ride, verify its documents and can also make the final payment through a contactless medium.




eco

TVS iQube First Ride Review: TVS’ second innings in electric scooter territory looks a promising one!

During its second innings in the EV space, TVS is quite confident with the iQube and why not! In this review, we tell you is TVS' latest offering has got what it takes to be a worthy all-rounder.




eco

Warren Buffett recites history to prove ‘nothing can stop America’: Coronavirus can’t kill economy

Warren Buffett on Saturday took a dive into the 231-year history of the United States of America to predict the future of the country’s economy struggling to stay on its feet amid the struggle against coronavirus and lockdown: “Nothing can basically stop America.”




eco

Gold prices hit fresh record highs twice in April; IMF cautions recession worse than 1930

Despite gold’s stellar performance, the precious metal is still very likely in the early stages of this remarkable bull market cycle.




eco

Asian stocks, oil higher as economies emerge from coronavirus lockdown

In reduced trade, with China, Japan and South Korea on holiday, Australia's ASX 200 rose 1.26% and Hong Kong's Hang Seng climbed 0.66%.




eco

Gold prices fall today after gaining Rs 1,000 in last two sessions on hopes of economic revival

The expectation of revival of economies after the lockdown and selling of gold by the central bank created pressure on the yellow metal




eco

Cotton Corporation purchases record 7.5L bales from Gujarat growers

According to an official source, CCI had purchased more than 13 lakh bales in 2008 as that year too, cotton prices had nosedived due to the global recession.




eco

Connected future: Digital to spearhead India’s $5 trillion economy ambition

Digital technologies have the potential to create $1 trillion economic value, says EY




eco

Cyberattacks get a new dimension: Political and economic intentions of cybercriminals

Threat trends show political and economic intentions of cybercriminals.




eco

How Edge computing is fast becoming a base for most IoT devices

Edge computing is the way forward, but are we ready to surrender control to corporations.




eco

Covid-19 and highway sector: Take the highway to recovery

Easing financial burden, preventing project failures and protecting jobs are a must if sector’s to preserve its health.




eco

Pink bollworm attack on cotton crosses economic threshold limit in Maharashtra

Last year’s cotton sowing was estimated at 126.44 lakh hectare. Scientists say that early cotton sowing may be responsible for pink bollworm attack.