A new program supporting young innovators in regional Australia is launched by the ABC and the Department of Infrastructure and Regional Development.

ABC is bringing back "The Wonderful World of Disney" this summer with a quartet of titles from the Disney Plus film catalogue. The network has announced that it will air "Moana," "Thor: The Dark World," "Up" and "Big Hero 6" across four Wednesdays this summer, starting with the world broadcast debut of the Auliʻi Cravalho […]

Accelerated bridge construction (ABC) utilizes rigorous planning, new technologies, and improved methods to expedite construction. Prefabricated columns and their connections to adjoining bridge members (cap beams, footings, pile caps, and pile shafts) are the most critical components of ABC in moderate- and high-seismic regions. The TRB National Cooperative Highway Research Program's NCHRP Research Report 935: Proposed AASHTO Seismic Specifications for ABC Column Connections develops AASHTO specificatio...

"America's Funniest Home Videos" will resume the remainder of season 30 the following week at 7:00/6:00c.

"I think I'm the only candidate who's prepared to take on the billionaire class," Sanders, I-Vt., told ABC's George Stephanopoulos on "This Week." "We need a political revolution in this country involving millions of people who are prepared to stand up and say, enough is enough, and I want to help lead that effort." Continue reading →

Australia's best known diversified entertainment group, Tabcorp, has successfully completed its move to a shared services model for finance, human resources and procurement with the assistance of IBM Global Business Services.

1. ABC’s Four Corners to investigate NRL’s financial woes  Daily Telegraph
2. Report: Rugby league players to be forced to decide between state and Test level footy  Wide World of Sports
3. NRL 2020: Peter V’landys set to cut $50m from League Central  Courier Mail
4. How a farm system could help the NRL expand  The Roar
5. View Full coverage on Google News

Playing to 130,000 online, with a virtual tip jar: Performers adapt to life under coronavirus  ABC News

1. Little Richard, rock pioneer behind hits Long Tall Sally, Tutti Frutti, dies aged 87  ABC News
2. Rock legend Little Richard dead at 87  NEWS.com.au
3. Little Richard, Flamboyant Rock and Roll Pioneer, Dies at 87  9Honey
4. Little Richard, flamboyant rock 'n' roll pioneer, dies at 87  The Times of Israel
5. Musician Little Richard dies aged 87  Sky News Australia
6. View Full coverage on Google News

1. In the midst of the coronavirus pandemic, China forces out foreign reporters  ABC News
2. China relations: ‘National security cowboys’ put nation’s interests at unnecessary risk  The Australian
3. Chinese buyers abandon Australian property, replaced by US investors: FIRB report  Domain News
4. Four Things to Know About China's Foreign-Investor Programs  Caixin Global
5. China to scrap foreign investment quotas in financial markets to lure more capital  The Star Online
6. View Full coverage on Google News

1. Queen Elizabeth's VE Day speech says veterans would be proud of coronavirus effort today  ABC News
2. Queen’s VE Day TV address: Tells Brits to ‘never give up’  NEWS.com.au
3. 'Streets filled with love': The Queen gets personal in VE Day broadcast  Sydney Morning Herald
4. King George VI VE Day speech: Read poignant message 'Our will-power is inexhaustible'  Express
5. A message of hope in difficult times  Telegraph.co.uk
6. View Full coverage on Google News

1. Coronavirus cases continue rise due to meatworks cluster as Victorians wait for restrictions to be eased  ABC News
2. Coronavirus: Victorian restrictions in place, Daniel Andrews waits  NEWS.com.au
3. 'Only ones who can’t celebrate Mother’s Day': Liberal MPs and senators critical of Victoria lockdown  Sydney Morning Herald
4. Government tries to play down 'childish' coronavirus attack on Victorian premier  SBS News
5. Cedar Meats outbreak reaches 75 as authorities investigate animal cruelty  The Age
6. View Full coverage on Google News

1. Coronavirus restrictions to lift in NSW from Friday, but will not be following all National Cabinet measures  ABC News
2. Berejiklian's roadmap to freedom in NSW  Sydney Morning Herald
3. Mother's Day state by state: What can and can't you do?  The Canberra Times
4. Permission to mingle: NSW will ease lockdown laws on Friday  Daily Telegraph
5. NSW to ease lockdown restrictions from Friday  The Age
6. View Full coverage on Google News

I was down to cook lunch on Sunday but there was so much food left over after the Braai I had a very easy job I did help Remi make veggie tempura for supper which we deep fried once in the afternoon then refried after the evenings survey. As it was Re

UCLA coach Mick Cronin has been selected the National Assn. of Basketball Coaches District 19 coach of the year, it was announced Monday.

What's on TV Tuesday, April 28: What's on TV Tuesday: 'Bless the Mess' on ABC; Coronavirus TV specials; talk shows; movies on TV and more

This month’s school closures have forced families to become teachers at home overnight. 

South Africa's broadcasting regulator has approved an application from the SABC for its annual local TV content quotas to be waived because of the Covid-19 coronavirus pandemic.

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.

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.

Taylor Swift announced her City of Lover concert, which took place in Paris, will air on ABC on May 17 at 10 p.m.

Paris : J.-B. Baillière, 1893.

George Karabatsos, Fabrizio Leisen.

Source: Statistics Surveys, Volume 12, 66--104.

Abstract:
We are living in the big data era, as current technologies and networks allow for the easy and routine collection of data sets in different disciplines. Bayesian Statistics offers a flexible modeling approach which is attractive for describing the complexity of these datasets. These models often exhibit a likelihood function which is intractable due to the large sample size, high number of parameters, or functional complexity. Approximate Bayesian Computational (ABC) methods provides likelihood-free methods for performing statistical inferences with Bayesian models defined by intractable likelihood functions. The vastity of the literature on ABC methods created a need to review and relate all ABC approaches so that scientists can more readily understand and apply them for their own work. This article provides a unifying review, general representation, and classification of all ABC methods from the view of approximate likelihood theory. This clarifies how ABC methods can be characterized, related, combined, improved, and applied for future research. Possible future research in ABC is then outlined.

Visions 2020: Nydia Han and 6abc celebrates Asian Pacific American Heritage Month - 6abc  WPVI-TV

When Berlin Brandenburg Airport is put into operation at the end of October 2020, Schönefeld Airport will become Terminal 5 (T5) of BER. In order to avoid duplicate names of terminal sections, gates and car parks at BER, the building and car park infras...

Celtic Connections

Neonatal respiratory distress syndrome is the most common respiratory cause of mortality and morbidity among US infants aged <1 year. Although neonatal respiratory distress syndrome is a heritable disorder, common genetic variants do not fully explain disease heritability.

Single ABCA3 mutations are overrepresented among term and late preterm (≥34 weeks’ gestation) European-descent infants with RDS. Although ABCA3 mutations are individually rare, they are collectively common in the European- and African-descent general population, present in ~4% of individuals. (Read the full article)

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The terminal sections and car parks at Schönefeld Airport will be given new names at the end of March. When Berlin Brandenburg Airport is put into operation at the end of October 2020, Schönefeld Airport will become Terminal 5 (T5) of BER. In order to a...

In 2012, mathematician Shinichi Mochizuki produced a proof claiming to solve the long-standing ABC conjecture, but no one understood it. Most mathematicians still don't, but it will now be published in a journal

ABSTRACT

The wall teichoic acid (WTA) is a major cell wall component of Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common cause of fatal clinical infections in humans. Thus, the indispensable ABC transporter TarGH, which flips WTA from cytoplasm to extracellular space, becomes a promising target of anti-MRSA drugs. Here, we report the 3.9-Å cryo-electron microscopy (cryo-EM) structure of a 50% sequence-identical homolog of TarGH from Alicyclobacillus herbarius at an ATP-free and inward-facing conformation. Structural analysis combined with activity assays enables us to clearly decode the binding site and inhibitory mechanism of the anti-MRSA inhibitor Targocil, which targets TarGH. Moreover, we propose a "crankshaft conrod" mechanism utilized by TarGH, which can be applied to similar ABC transporters that translocate a rather big substrate through relatively subtle conformational changes. These findings provide a structural basis for the rational design and optimization of antibiotics against MRSA.

IMPORTANCE The wall teichoic acid (WTA) is a major component of cell wall and a pathogenic factor in methicillin-resistant Staphylococcus aureus (MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-Å cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a "crankshaft conrod" mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.

ABSTRACT

This research analyzed six Aspergillus fumigatus genes encoding putative efflux proteins for their roles as transporters. The A. fumigatus genes abcA, abcC, abcF, abcG, abcH, and abcI were cloned into plasmids and overexpressed in a Saccharomyces cerevisiae strain in which the highly active endogenous ABC transporter gene PDR5 was deleted. The activity of each transporter was measured by efflux of rhodamine 6G and accumulation of alanine β-naphthylamide. The transporters AbcA, AbcC, and AbcF had the strongest efflux activities of these compounds. All of the strains with plasmid-expressed transporters had more efflux activity than did the PDR5-deleted background strain. We performed broth microdilution drug susceptibility testing and agar spot assays using an array of compounds and antifungal drugs to determine the transporter specificity and drug susceptibility of the strains. The transporters AbcC and AbcF showed the broadest range of substrate specificity, while AbcG and AbcH had the narrowest range of substrates. Strains expressing the AbcA, AbcC, AbcF, or AbcI transporter were more resistant to fluconazole than was the PDR5-deleted background strain. Strains expressing AbcC and AbcF were additionally more resistant to clotrimazole, itraconazole, ketoconazole, and posaconazole than was the background strain. Finally, we analyzed the expression levels of the genes by reverse transcription-quantitative PCR (RT-qPCR) in triazole-susceptible and -resistant A. fumigatus clinical isolates. All of these transporters are expressed at a measurable level, and transporter expression varied significantly between strains, demonstrating the high degree of phenotypic variation, plasticity, and divergence of which this species is capable.

IMPORTANCE One mechanism behind drug resistance is altered export out of the cell. This work is a multifaceted analysis of membrane efflux transporters in the human fungal pathogen A. fumigatus. Bioinformatics evidence infers that there is a relatively large number of genes in A. fumigatus that encode ABC efflux transporters. However, very few of these transporters have been directly characterized and analyzed for their potential role in drug resistance.

Our objective was to determine if these undercharacterized proteins function as efflux transporters and then to better define whether their efflux substrates include antifungal drugs used to treat fungal infections. We chose six A. fumigatus potential plasma membrane ABC transporter genes for analysis and found that all six genes produced functional transporter proteins. We used two fungal systems to look for correlations between transporter function and drug resistance. These transporters have the potential to produce drug-resistant phenotypes in A. fumigatus. Continued characterization of these and other transporters may assist in the development of efflux inhibitor drugs.