23 February 2015

"Passing along a message from Mother Nature," the National Weather Service in Binghamton, New York, tweeted alongside a photo of a car covered in light snow. "Happy Mother's Day Weekend."

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.

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.

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.

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.

BRIDGETOWN, Barbados (CMC): Former top West Indies cricket administrator, 76-year-old Deryck Murray, has warned against a forced restart of cricket amid the current challenges posed by the deadly coronavirus pandemic, and says any premature actions...

Lady Allen – wife of Jamaica’s Governor General Sir Patrick Allen – says Jamaican women are among the strongest and most resilient in the world, and despite many bearing the full brunt of the coronavirus pandemic as breadwinners for their families...

This edited volume develops a pragmatic approach to the engagement of highly skilled members of the diaspora for the benefit of their countries of origin. The book, edited by a World Bank senior economist, is based on empirical work in middle-income and high-income economies.

He catches the fish, breathes on them, then throws them back. These infected fish will infect all bodies of water with Covid-19. He goes saltwater and fresh water fishing 

I’ve liked him for a year and I told him, but he told me to date someone else. I started to forget about him, but then he told me that he liked me too. We’re dating now but I don’t think that I feel the same was as when I first started liking him. What should I do?

I have a fwb trade with this guy who doesnt respect me at all and hurts my feelings because I'm not as attractive as he is and gets annoyed if I dont meet his demands,how do I stop this fwb? I'm scared if he does he'll tell people or get mad at me.

I'll try to keep this short: So I have always dated guys. Yet when I am not dating guys, my best friend and I; who's a girl, hook up. We've been doing this for about 5 years, we met at the age of 15, and 5 yrs later I had my first lesbian experience with her, and then 5 years it became a fairly regular thing. 5 years is obviously a long time. But when I'm not dating a guy, I always go back to her. And she's the only woman I have ever been with. That's why I am confused about this. I do not know if I'm straight or a lesbian?

Chronic rejection of transplanted organs is the leading cause of transplant failure, and one that the field of organ transplantation has not overcome in almost six decades since the advent of immunosuppressive drugs enabled the field to flourish.

(May 7, 2020) On February 18, 2020, Paraguayan President Mario Abdo Benítez signed Law No. 6501/2020, amending Law No. 4743/2012 Regulating Political Financing. Law No. 6501 creates a unit within the Superior Court of Electoral Justice (Tribunal Superior de Justicia Electoral, TSJE) to be in charge of arranging, coordinating, and supervising policies and procedures to prevent […]

(May 7, 2020) On April 30, 2020, Singapore’s minister for health made an amendment to the COVID‑19 (Temporary Measures) (Control Order) Regulations 2020 to extend the expiration date of the COVID-19 control orders under the regulations to June 1, 2020. The Control Order Regulations, which had been originally issued on April 7, 2020, under the authorization […]

Filmfare recommends: Bollywood films revolving around journalism  Filmfare

Amid lockdown crisis, Guwahati NGO lends helping hand to musicians  Northeast Now

Personal Agenda with Ricky Kej: “Best thing about lockdown? My dog is really happy!”  Hindustan Times

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

For the past few weeks, Windsor's new pandemic response therapist Dana St. Jean has been spending her time fielding phone calls and speaking with people over video chat to find ways to help them cope with the stresses of COVID-19.

OM Turkey helps the local church to minister to the 2.6 million refugees in their country.

Over 50 pastors and family members from Tacloban enjoy a weekend getaway organised by OM Philippines from 7-9 March.

Michel Di Feliciantonio and three other Italian Christians spent a week in Šid, Serbia, helping refugees on their way into Europe.

God uses football and English lessons to build friendships between OM Serbia and refugees.

OM Serbia, with the help of volunteers from several nations, are providing sweet tea, and friendship, to the refugees at a camp in Sid, Serbia.

Catherine, from the UK, joined an OM team in July to host a dental clinic and outreach for the residents of Pădureni.

“Every movie, book or song tells a story. They all have a beginning and an end. When a song ends, the story seems over. When the killer is found at the end of that thriller, the movie ends. When the couple is finally together and they kiss on the last page of that romance novel, the book ends,” says OMer Anja. “But in life, the end of a story is never the end of it. It always goes on. When that book or movie is over, time seems to freeze and life as we know it seems to stay exactly the same.”

Seventeen participants from nine churches gather for OM Malaysia and OM Singapore's Life Direction Weekend in Port Dickson, Malaysia, from 21-23 March.

When an OM Lifehope team, partnering with On the Move International, held their annual community barbeque, they did something a little different.

Community encounter teams seek to serve their local communities and bring Jesus to their neighbourhoods.

With a cultural theme on Latin America, 231 participants from 40 countries have come together for the September GO conference in the Netherlands.

REACTION poured in following the death of rock 'n' roll pioneer Little Richard, who died yesterday at age 87.

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.

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.

Source: www.reuters.com - Saturday, May 09, 2020
Malaysia's government extended the time frame for movement and business curbs by another four weeks to June 9, amid a gradual reopening of economic activity stunted by the coronavirus pandemic.

OM Finland extends love and fellowship to immigrant mothers through friendship groups, open conversation and learning together.

“As I watched the ending scene (that lasted about three minutes) I thought about the “happy ending” notion,” says Ava. “Is it real or is it a fairy tale? A utopia created by Hollywood to give their viewers a false sense of hope in the reality of a broken world? And so, I said to myself: I believe in happy endings.”

Twenty-three people from Czech Republic attend an OM missions weekend held at the team base in České Budějovice in April.

“As I watched the ending scene (that lasted about three minutes) I thought about the “happy ending” notion,” says Ava. “Is it real or is it a fairy tale? A utopia created by Hollywood to give their viewers a false sense of hope in the reality of a broken world? And so, I said to myself: I believe in happy endings.”

Something unintentionally funny keeps happening on the politically feverish fringes of Scottish social media.

Source: www.inquisitr.com - Saturday, May 09, 2020
Little Richard, real name Richard Wayne Penniman, has died at the age of 87, per Rolling Stone . The performer’s cause of death is unknown. Little Richard Dead, Legendary Musician Dies At 87 is an article from: The Inquisitr Click here to continue and read more...

“As I watched the ending scene (that lasted about three minutes) I thought about the “happy ending” notion,” says Ava. “Is it real or is it a fairy tale? A utopia created by Hollywood to give their viewers a false sense of hope in the reality of a broken world? And so, I said to myself: I believe in happy endings.”

Penn State Altoona's Alumni Society is mailing "graduation goodie" packages to each of the college's 200 graduating seniors.

As part of Penn State’s 2020 spring commencement activities, Clara Miller will represent the Department of Women’s, Gender, and Sexuality Studies in the College of the Liberal Arts as its student marshal.

“As I watched the ending scene (that lasted about three minutes) I thought about the “happy ending” notion,” says Ava. “Is it real or is it a fairy tale? A utopia created by Hollywood to give their viewers a false sense of hope in the reality of a broken world? And so, I said to myself: I believe in happy endings.”