When I was sports editor for the college newspaper, I wrote a column that was, I'm sure now a decade removed, far less clever than I thought it was at the time. But since I am 1) pressed for time and 2) devoid of original thought at the moment, I present to you, dear reader, a special reprisal of the Michael Harris Daily Weekly Monthly Occasional Grab Bag of Sports Hydropower Stuff.

As originally published in React News Beijing is determined all outgoing investment will align with China’s strategic goals Stockholm - home of ABBA and fermented herring. A fish so pongy, the Swedes o...

A stray kitten climbed into the engine of a car in Otara, south Auckland, and ended up hitching a ride all the way to West Harbour, in west Auckland, where it was rescued and adopted by a loving family.It was early on Saturday morning...

Diyaaraddii ku buburtey Berdaale ee nooceedu ahaa xamuulka ayaa la xaqiijiyey in ciidamada Itoobiya ee halkaas ku sugan ay ku rideen hubka lidka diyaaradaha kadibna sidaas ku burburtey. War ka soo baxay AMISOM ee la xiriira baaritaanka wada jirka ah ee la sameynaayey ayaa lagu sheegay in diyaaradda aysan soo ridin ciidamada AMISOM ee ay […]

The post Diyaaraddii Berdaale ku dhacdey oo la xaqiijiyey in Ciidamada Itoobiya soo rideen appeared first on Horseed Media • Somali News.

Table tennis star Mima Ito was disappointed by the postponement of the Tokyo Olympics, due to the COVID-19 outbreak, because it took away the chance ...

President Donald Trump laid into some of his close Senate allies for siding with Democrats on an Iran war powers bill even as Congress failed to override his veto.

Would you go on the run with your ex?

Chinese ride-hailing giant Didi Chuxing’s core business has been profitable, president Jean Liu Qing said for the first time, as ride orders in its domestic market recover from the impact of the coronavirus pandemic.In a rare interview, Liu told the CNBC that Didi’s core business has been profitable, without providing specific figures or explaining how or when the company had measured its profitability. The company has no plans for job cuts or raising capital, Liu said in the interview that…

A former Pakistani child bride, who was wrongly accused of killing her husband at 13 and subsequently spent almost two decades in prison, is making history by being the first victim of a miscarriage of justice to seek compensation from the state, say legal human rights experts.   This March, Rani Tanveer, who was released in […]

The post Former Child Bride Holds Pakistan to Account for Wrongful Imprisonment in Historic Legal Challenge appeared first on Inter Press Service.

Sridevi died on February 24, 2018 and Irrfan Khan passed away on April 29, 2020

WASHINGTON: The US Senate on Thursday failed to override President Donald Trump’s veto of a bipartisan measure that would have limited his power to attack Iran. Lawmakers voted 49-44 to support the resolution that passed Congress earlier this year, short of the two-thirds majority necessary...

The ‘app economy’ provides potential risks and benefits for developing countries. The right policies are needed to bring out the best in these emerging economic trends.

There's a home in Telluride that would make Flo from Progressive proud.

A new book from Jim Al-Khalili makes cutting-edge physics easily understandable and makes it clear why he fell in love with the subject as a teenager

The fifth season of the ABB FIA Formula E Championship has kicked off in style in December 2018 with the SAUDIA Ad Diriyah E-Prix. Since then, the Championship’s 22 participating Gen2 electric cars and drivers have been crisscrossing the planet in 13...

Title: Study Makes Strides in Understanding Ovarian Cancer
Category: Health News
Created: 4/26/2010 6:10:00 PM
Last Editorial Review: 4/27/2010 12:00:00 AM

Title: Health Tip: Taking the Kids for a Shopping Cart Ride
Category: Health News
Created: 5/1/2012 8:05:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: More Than 4,000 U.S. Kids Hurt Each Year on Amusement Rides
Category: Health News
Created: 5/1/2013 10:35:00 AM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: U.S. Lowers Recommended Fluoride Levels in Drinking Water
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

Title: Health Tip: Enjoy a Healthier Plane Ride
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Ride-Sharing Services Tied to Rise in Car Crashes
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

ABSTRACT

One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa. Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans. We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides.

IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.

ABSTRACT

Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs.

IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.

ABSTRACT

The Candida albicans high-affinity phosphate transporter Pho84 is required for normal Target of Rapamycin (TOR) signaling, oxidative stress resistance, and virulence of this fungal pathogen. It also contributes to C. albicans’ tolerance of two antifungal drug classes, polyenes and echinocandins. Echinocandins inhibit biosynthesis of a major cell wall component, beta-1,3-glucan. Cells lacking Pho84 were hypersensitive to other forms of cell wall stress beyond echinocandin exposure, while their cell wall integrity signaling response was weak. Metabolomics experiments showed that levels of phosphoric intermediates, including nucleotides like ATP and nucleotide sugars, were low in pho84 mutant compared to wild-type cells recovering from phosphate starvation. Nonphosphoric precursors like nucleobases and nucleosides were elevated. Outer cell wall phosphomannan biosynthesis requires a nucleotide sugar, GDP-mannose. The nucleotide sugar UDP-glucose is the substrate of enzymes that synthesize two major structural cell wall polysaccharides, beta-1,3- and beta-1,6-glucan. Another nucleotide sugar, UDP-N-acetylglucosamine, is the substrate of chitin synthases which produce a stabilizing component of the intercellular septum and of lateral cell walls. Lack of Pho84 activity, and phosphate starvation, potentiated pharmacological or genetic perturbation of these enzymes. We posit that low substrate concentrations of beta-d-glucan- and chitin synthases, together with pharmacologic inhibition of their activity, diminish enzymatic reaction rates as well as the yield of their cell wall-stabilizing products. Phosphate import is not conserved between fungal and human cells, and humans do not synthesize beta-d-glucans or chitin. Hence, inhibiting these processes simultaneously could yield potent antifungal effects with low toxicity to humans.

IMPORTANCE Candida species cause hundreds of thousands of invasive infections with high mortality each year. Developing novel antifungal agents is challenging due to the many similarities between fungal and human cells. Maintaining phosphate balance is essential for all organisms but is achieved completely differently by fungi and humans. A protein that imports phosphate into fungal cells, Pho84, is not present in humans and is required for normal cell wall stress resistance and cell wall integrity signaling in C. albicans. Nucleotide sugars, which are phosphate-containing building block molecules for construction of the cell wall, are diminished in cells lacking Pho84. Cell wall-constructing enzymes may be slowed by lack of these building blocks, in addition to being inhibited by drugs. Combined targeting of Pho84 and cell wall-constructing enzymes may provide a strategy for antifungal therapy by which two sequential steps of cell wall maintenance are blocked for greater potency.

ABSTRACT

Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2'-fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.)

IMPORTANCE Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.

ABSTRACT

Lipopolysaccharide (LPS) is an essential glycolipid present in the outer membrane (OM) of many Gram-negative bacteria. Balanced biosynthesis of LPS is critical for cell viability; too little LPS weakens the OM, while too much LPS is lethal. In Escherichia coli, this balance is maintained by the YciM/FtsH protease complex, which adjusts LPS levels by degrading the LPS biosynthesis enzyme LpxC. Here, we provide evidence that activity of the YciM/FtsH protease complex is inhibited by the essential protein YejM. Using strains in which LpxC activity is reduced, we show that yciM is epistatic to yejM, demonstrating that YejM acts upstream of YciM to prevent toxic overproduction of LPS. Previous studies have shown that this toxicity can be suppressed by deleting lpp, which codes for a highly abundant OM lipoprotein. It was assumed that deletion of lpp restores lipid balance by increasing the number of acyl chains available for glycerophospholipid biosynthesis. We show that this is not the case. Rather, our data suggest that preventing attachment of lpp to the peptidoglycan sacculus allows excess LPS to be shed in vesicles. We propose that this loss of OM material allows continued transport of LPS to the OM, thus preventing lethal accumulation of LPS within the inner membrane. Overall, our data justify the commitment of three essential inner membrane proteins to avoid toxic over- or underproduction of LPS.

IMPORTANCE Gram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli. Here, we show that YejM inhibits activity of the YciM/FtsH protease complex, which regulates synthesis of the essential OM glycolipid lipopolysaccharide (LPS). Our data suggest that disrupting proper communication between LPS synthesis and transport to the OM leads to accumulation of LPS within the inner membrane (IM). The lethality associated with this event can be suppressed by increasing OM vesiculation. Our research has identified a completely novel signaling pathway that we propose coordinates LPS synthesis and transport.

ABSTRACT

All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the "decorations" of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called "EPA decorations" consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor.

IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called "EPA decorations" essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci.

Key Points

Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.

Alex, Kelley, Nathan, and Peter have all descended into the slums of Midgar, so the Final Fantasy VII Remake dominates our Now Playing, but Anna Marie still manages to answer a question left over from last week about Persona 5 Royal. Our listeners recount their memories of the original FF7 and we even manage to squeak in some news of the week too.

Mazda Motor Corp has sought loans totalling about 300 billion yen ($2.8 billion) from Japan's three megabanks and other lenders to ride out the coronavirus epidemic, a source with direct knowledge of the matter said on Saturday.

War veteran Captain Tom Moore, who has raised £28 million for the NHS by walking lengths of his garden, has been given a Pride of Britain award.

A five-year-old boy who was caught behind the wheel of his parents' car "driving to California to buy a Lamborghini" has been given a ride in his dream car by a kind stranger.

The Senate failed to override President Trump's veto of legislation that would have prevented him from taking military action in Iran without congressional approval. On Thursday, the Senate voted 49-44 in favor of the override, falling short of the two-thirds majority needed for it to be approved. Both chambers of Congress passed the bipartisan resolution earlier this year.

The Senate failed to override President Trump's veto of legislation that would have prevented him from taking military action in Iran without congressional approval. On Thursday, the Senate voted 49-44 in favor of the override, falling short of the two-thirds majority needed for it to be approved. Both chambers of Congress passed the bipartisan resolution earlier this year.

Uber on Wednesday said it would lay off 3,700 full-time employees, or roughly 17 per cent of its head count.

By Frank Moher On this dreadful day, I don’t want to write about the shootings in Orlando. I want to write about my friend, Rick. Rick lives just outside of Nanaimo, a city of about 80,000, across the water from the island I live on. He’s been a celebrity there for a long time, first as the city’s […]

Show stars Warren as the eponymous detective solving crime on the streets of Amsterdam

Lyft users must self-certify that they are following CDC guidelines related to COVID-19.

Social distancing rules will ‘kill cities’, experts warn – and the future of mass transit hangs in the balance

This is the second feature in our Life after lockdown series, which looks at how Covid-19 could change Australia for good

Before the pandemic struck, Sara Blazey made the same three-hour commute to work, three days a week, for the better part of 12 years. The 63-year-old family lawyer from the Blue Mountains works for a domestic violence legal advice hotline in Parramatta and it used to be that she would wake at 7am, drive seven minutes to Hazelbrook station and from there catch the 7.17am train to Parramatta before making the same one-and-a-half hour trip home in the evening.

With the pandemic, all that would change. Domestic violence support services such as the one Blazey worked for were declared “essential” services, meaning they could keep operating despite restrictions. To ensure they could do so safely, the organisation did what some commentators long thought impossible and began to transition its employees into working from home.

Sydney beats Montreal and Houston in its bid to host WorldPride in 2023, becoming the first city in the southern hemisphere to host the major international LGBTQI event.

Responding to a new California labor law, Uber making concessions drivers have long sought. But it may change the service in ways that displease drivers and riders alike.

L’UFC s’apprête à reprendre ses combats, à huis clos, samedi à Jacksonville, sept semaines après l’arrêt forcé des compétitions sportives.

Jenny and her mum Jacky have very different ideas about what she should wear on her big day - so they turn to Gok Wan for help

St George Illawarra coach Paul McGregor has turned to two of the Dragons' fiercest competitors to help restore pride and passion to the club.

The new documentary "Spaceship Earth" breaks the mystery of the Biosphere 2 experiment wide open, revealing the facts in a story that feels more like science fiction than reality.

As coronavirus puts the brakes on many public events, equestrian competitions move with the times — and go online.