It follows criticism that a move away from the "stay at home" slogan could confuse the public.

V družstevních bytech žije přibližně 10 procent českých domácností. Vzhledem k rostoucím cenám nemovitostí je tento typ bydlení oproti osobnímu vlastnictví dostupnější, a zažívá tak další vlnu rozvoje. Družstevní vlastnictví má ale svá specifika. Pokud o koupi družstevního bytu uvažujete, ověřte si své znalosti v dnešním kvízu.

"Shhh, You'll wake Ginny up, James," Teddy Lupin whispered to the three-year-old James, who was looking at Teddy with a sheepish look... R&R!

Thanks, Tupperware!

cloud-sailing:

Santiago, Chile by So Cal Metro on Flickr.

Check out travel recommendations at Wanderfly!

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modernmoon:

france,etretat by ZulfiyaG on Flickr.

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Theories developed at Princeton University led to the creation of time crystals reported in the journal Nature March 9 by two groups of researchers based at Harvard University and the University of Maryland. Time crystals feature atoms and molecules arranged across space and time and are opening up entirely new ways to think about the nature of matter. They also eventually may help protect information in futuristic devices known as quantum computers.

Environmental News FOR IMMEDIATE RELEASE

VICTORY for the Lions yesterday morning courtesy of a stirring late comeback against the All Blacks was magnificent sporting theatre and the perfect result to set up a series decider next weekend.

Tight end who scored 16 touchdowns for the Boilermakers is picked by the Los Angeles Rams in the fourth round.

Prior to joining the Boilermakers, Elliott Cribby served as pitching coach and recruiting coordinator at Seattle University.

Markus Bailey missed most of his senior season with a knee injury but he started 40 games for the Boilermakers.

COVID-19 has been more prevalant in Quebec's women than men, unlike many other of the world's regions according to data published by the Quebec Institute of Public Health on Saturday.

Laurie Few knew their time with her father Allan was short when he tested positive for COVID-19 last Sunday.

Social distancing could mean prayer books cannot be shared and people cannot sing, religious leaders say.

Messages to mothers and words of support were front and centre as Edmontonians cruised by MacTaggart Place retirement residence on Saturday afternoon.

Former New Zealand head coach and current England defence chief John Mitchell believes some good may come for rugby union from the coronavirus.

The DML News App offers the best in news reporting.

The post REPORT: Rock vocalist’s daughter rescued from Peru by US Embassy amid coronavirus ban appeared first on Dennis Michael Lynch.

The following article, OUCH! Michelle Obama’s Netflix Documentary “Becoming” Gets Panned By Critics, was first published on 100PercentFedUp.com.

Unlike Melania Trump, who’s yet to appear on the cover of a major fashion magazine since becoming America’s First Lady, Michelle Obama has always been given special treatment by the far-left media, who couldn’t put her face on enough magazine covers. When her “Becoming” documentary aired on Wednesday, it was probably expected that the media […]

Continue reading: OUCH! Michelle Obama’s Netflix Documentary “Becoming” Gets Panned By Critics ...

31 July 2014 , Volume 70, Number 4

Branding the country a failed state is unhelpful

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.

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.

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.

Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.

Declaring it has been “pained” by the Jodian Fearon situation, the embattled Andrews Memorial Hospital (AMH) is speaking out, saying it has never been approached for or rejected efforts at registration or certification since it began operating 76...

New research provides evidence for the idea that sleep restores cellular homeostasis in the brain and helps us to forget irrelevant information

We spend one third of our lives sleeping, but we still do not know exactly why we sleep. Recent research shows that that the brain does its housekeeping while we sleep, and clears away its waste. According to another hypothesis, sleep plays the vital role of restoring the right balance of brain synapses to enhance learning, and two studies published in today’s issue of Science now provide the most direct evidence yet for this idea.

We do know that sleep is important for consolidating newly formed memories. During waking hours, we learn all kinds of new information, both consciously and unconsciously. To store it, the brain modifies large numbers of synaptic connections, making some of them stronger and larger, and it’s now thought that as we sleep other synapses are weakened or destroyed, so that the important new information is stored for later use, while irrelevant material, which could interfere with learning, is not.

Related: The Homer Simpson effect: forgetting to remember

Related: How to optimise your brain's waste disposal system

Joe Haggerty revisits the Boston Bruins' 2017 NHL Draft and hands out a grade for each of their picks.

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

On Mother’s Day, be inspired by these mother-daughter duos who are going places  YourStory

A Calgary coffee shop must close public access to its patio and dine-in services, Alberta Health Services says.

Typically, at least two discarded babies are found in the Mamelodi City Dump every week. AIDS Hope seeks to eliminate this horrible reality.

Opening a ‘baby safe’ in a township near Pretoria, South Africa, helps desperate mothers find a solution and give their babies a future.

For the past two years OM South Africa SportsLink has attended a prestigious rugby tournament to spread the good news to players, coaches and staff.

A girl named Anastasia, growing up between alcoholics and drug addicts, is reunited with her father who years before became a Christian.

Students of OM Russia's Discipleship Centre learn not only through theory but by hands-on practical experience.

Antonio Nipueda (Mozambique) recollects his journey to ministry with OM in Mozambique and the ways their prayers have impacted one village there.

Used by God beyond her skills as a dentist, an outreach participant shares the gospel with a disabled woman, whose life is forever changed.

As a grandmother with some serious health issues and limited knowledge of Spanish and English, Francine wondered whether God could use her in Spain.

God uses bracelets to weave together a group of children from different cultures and backgrounds so they can experience His love.

A Zambian worker reaches out with love to the people of Somalia living in his country.

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.

African women who never went to school were unable to read the Bible upon becoming Christ followers. A new opportunity is giving them access to God's Word firsthand.

African women who never went to school were unable to read the Bible upon becoming Christ followers. A new opportunity is giving them access to God's Word firsthand.

African women who never went to school were unable to read the Bible upon becoming Christ followers. A new opportunity is giving them access to God's Word firsthand.