"The Farewell" made off with best picture as Zhao Shuzhen upset Jennifer Lopez and "Uncut Gems" claimed three prizes, including a win for Adam Sandler.

Dubai-based airline's policies now more generous than most carriers

Arsene Wenger believes Arsenal's move to the Emirates came at a cost.

PIRATES OF THE CARIBBEAN 6 may go ahead without Johnny Depp's Jack Sparrow and fans are having none of it.

MARTIN LEWIS was on hand to answer questions from the public during The Martin Lewis Money Show - A Coronavirus Special on ITV on Thursday evening. During the instalment, he addressed ISA and regular savings accounts.

LEGIONS of gardeners, wondering what has happened to the goods they have bought from online retailer Primrose, are set to receive refunds "within days", the company has confirmed.

Arsene Wenger believes Arsenal's move to the Emirates came at a cost.

Arsene Wenger believes Arsenal's move to the Emirates came at a cost.

PIRATES OF THE CARIBBEAN 6 is separate to a possible female-led spin-off, according to a Disney insider. We could be looking at two movies with Johnny Depp's Jack Sparrow returning.

PIRATES OF THE CARIBBEAN 6 may go ahead without Johnny Depp's Jack Sparrow and fans are having none of it.

A Nashville mom who gave birth to an 'alarmingly small' child celebrates her first Mother's Day with a healthy daughter and waves of gratitude.

British Crime Survey reveals the chances of being a victim of crime are lowest for 20 years.

Pirates have attacked two fishing vessels near the Gabonese capital Libreville, abducting six crewmen, a source close to the Gabonese government told AFP.

The 30-year fixed-rate average moved slightly higher this week, increasing to 3.26 percent.

Who actually owns and operates the most popular and your favourite cruise lines? Be prepared for some surprises as I take a look at who the biggest cruise lines in the world are based on number of passengers carried, and then who owns and controls the lines. Although there are many cruise lines, they are all pretty much owned by three large cruise corporations. Discover who owns and operates the cruise lines you have heard of, love or considering cruising with.

Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises.

Follow Tips For Travellers on:

Instagram: http://www.instagram.com/garybembridge

Facebook: http://www.facebook.com/tipsfortravellers

Twitter: http://www.twitter.com/garybembridge

Borrowing costs have stayed at or near record lows for five consecutive weeks.

Hear about travel to United Arab Emirates as the Amateur Traveler talks to travel writer Zora O'Neill about her recent trip to these small states on the Persian / Arabian Gulf.

Hear about travel to the United Arab Emirates (UAE) as the Amateur Traveler talks to Keri Hedrick from ourglobetrotters.com and familytravel-middleeast.com about her adopted country.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

Support from the Bill & Melinda Gates Foundation has enabled Chatham House to develop a global health security track at the Munich Security Conference (MSC).

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

K Schoonjans
May 1, 1996; 37:907-925
Reviews

Invitation Only Research Event

Event participants

Jude Webber, Mexico and Central America Correspondent, Financial Times
Michael Stott, Latin America Editor, Financial Times
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

Moacir Aloisio, Silas L. Carvalho and César R. de Oliveira
Proc. Amer. Math. Soc. 148 (2020), 2509-2523.
Abstract, references and article information

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

Children gain a valuable insight into Hong Kong’s waterworks by directing the flow of water at an attraction designed to emulate the water cycle at the Water Supplies Department’s brand new H2OPE Centre.

They learn how rain passes through catchwaters in mountains and is filtered and distributed to people’s homes at the attraction, one of the 54 games or displays at the water education centre.

Kids can also try their hand at a fishing simulator to learn about tips and advice on fishing in reservoirs and discover ways to recycle and save water at other exhibits of the 720-sq m centre, which opened in December.

“It is extremely fun. We do not have this at school. I know how to save water now,” student Kim Lam said.

“Usually, we sit in a classroom and answer questions. But now we can learn about water in Hong Kong by playing games. It is excellent,” fellow student Alan Zeng added.

Children can also watch immersive videos at the centre’s 3D dome theatre.

Deeper understanding

The department hopes the centre will raise public awareness about water conservation.

“Its exhibits, live demonstrations and interactive games help visitors gain more insight into Hong Kong’s water resources,” Water Supplies Department Senior Engineer Irene Tong explained.

People can also visit the city’s important waterworks facilities such as the Waterworks Heritage Trails and the High Island Reservoir in Sai Kung, by joining the department’s Excursion with Water Save Dave. 

Water Save Dave is the department’s mascot to help promote a water conservation culture in the community.

Water Supplies Department Engineer Fion Chan said: “Water Save Dave is blue and shaped like a water drop to encourage us to cherish every single drop of water.

“We hope that guided tours of waterworks facilities will raise the public’s awareness about water resources and conservation.”

(University of Southern Denmark) Investing in the future: Researchers show how cannibalism among the invasive comb jelly enables adults to survive severe conditions at the edge of their ecological range with implications for the use and evolutionary origins of cannibalism.

Teri L. Hernandez
May 1, 2016; 29:82-88
From Research to Practice

Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive. Recently developed mass spectrometry (MS)-based phosphoproteomic approaches have expanded the list of potential STPK substrate identifications, yet further investigation is required to define the most functionally significant phosphosites and their physiological importance. Prior to the application of MS workflows, for instance, GarA was the only known and validated physiological substrate for protein kinase G (PknG) from pathogenic mycobacteria. A subsequent list of at least 28 candidate PknG substrates has since been reported with the use of MS-based analyses. Herein, we integrate and critically review MS-generated datasets available on novel STPK substrates and report new functional and subcellular localization enrichment analyses on novel candidate protein kinase A (PknA), protein kinase B (PknB) and PknG substrates to deduce the possible physiological roles of these kinases. In addition, we assess substrate specificity patterns across different mycobacterial STPKs by analyzing reported sets of phosphopeptides, in order to determine whether novel motifs or consensus regions exist for mycobacterial Ser/Thr phosphorylation sites. This review focuses on MS-based techniques employed for STPK substrate identification in mycobacteria, while highlighting the advantages and challenges of the various applications.

Back once again like the Renegade Master, the UK Tech Weekly Podcast is coming to you from its new, earlier-in-the-week time slot.

Host Scott Carey is joined by Tamlin Magee to talk about pirate-obsessed Nigerian hacking syndicates, and Charlotte Jee is on board to discuss the ethics of facial (and racial) recognition technology.

We wrap things up with an Elon Musk news roundup, from his latest bae to building bricks.

See acast.com/privacy for privacy and opt-out information.

If your business key column is a name literal, like " business key "n, a syntax error occurs when that variable name does not follow standard SAS naming conventions.

Sodium glucose co-transporter-2 inhibitors (SGLT2i) have favorable cardiovascular outcomes in diabetic patients. However, whether SGLT2i can improve obesity-related cardiac dysfunction is unknown. Sestrin2 is a novel stress-inducible protein that regulates AMPK-mTOR and suppresses oxidative damage. The aim of this study was to determine whether empagliflozin (EMPA) improves obesity-related cardiac dysfunction via regulating Sestrin2-mediated pathways in diet-induced obesity. C57BL/6J mice and Sestrin2 knockout mice were fed a high-fat diet (HFD) for 12 weeks and then treated with or without EMPA (10 mg/kg) for 8 weeks. Treating HFD-fed C57BL/6J mice with EMPA reduced body weight, whole-body fat, and improved metabolic disorders. Furthermore, EMPA improved myocardial hypertrophy/fibrosis and cardiac function, and reduced cardiac fat accumulation and mitochondria injury. Additionally, EMPA significantly augmented Sestrin2 levels, increased AMPK and eNOS phosphorylation, but inhibited Akt and mTOR phosphorylation. These beneficial effects were partially attenuated in HFD-fed Sestrin2 knockout mice. Intriguingly, EMPA treatment enhanced the Nrf2/HO-1-mediated oxidative stress response, suggesting antioxidant and anti-inflammatory activity. Thus, EMPA improved obesity-related cardiac dysfunction via regulating Sestrin2-mediated AMPK-mTOR signaling and maintaining redox homeostasis. These findings provide a novel mechanism for the cardiovascular protection of SGLT2i in obesity.

Cardiac glucose uptake and oxidation are reduced in diabetes despite hyperglycemia. Mitochondrial dysfunction contributes to heart failure in diabetes. It is unclear if these changes are adaptive or maladaptive. To directly evaluate the relationship between glucose delivery and mitochondrial dysfunction in diabetic cardiomyopathy we generated transgenic mice with inducible cardiomyocyte-specific expression of the glucose transporter (GLUT4). We examined mice rendered hyperglycemic following low-dose streptozotocin prior to increasing cardiomyocyte glucose uptake by transgene induction. Enhanced myocardial glucose in non-diabetic mice decreased mitochondrial ATP generation and was associated with echocardiographic evidence of diastolic dysfunction. Increasing myocardial glucose delivery after short-term diabetes onset, exacerbated mitochondrial oxidative dysfunction. Transcriptomic analysis revealed that the largest changes, driven by glucose and diabetes, were in genes involved in mitochondrial function. This glucose-dependent transcriptional repression was in part mediated by O-GlcNAcylation of the transcription factor Sp1. Increased glucose uptake induced direct O-GlcNAcylation of many electron transport chain subunits and other mitochondrial proteins. These findings identify mitochondria as a major target of glucotoxicity. They also suggest reduced glucose utilization in diabetic cardiomyopathy might defend against glucotoxicity and caution that restoring glucose delivery to the heart in the context of diabetes could accelerate mitochondrial dysfunction by disrupting protective metabolic adaptations.

A failure in self-tolerance leads to autoimmune destruction of pancreatic β-cells and type 1 diabetes (T1D). Low molecular weight dextran sulfate (DS) is a sulfated semi-synthetic polysaccharide with demonstrated cytoprotective and immunomodulatory properties in vitro. However, whether DS can protect pancreatic β-cells, reduce autoimmunity and ameliorate T1D is unknown. Here we report that DS, but not dextran, protects human β-cells against cytokine-mediated cytotoxicity in vitro. DS also protects mitochondrial function and glucose-stimulated insulin secretion and reduces chemokine expression in human islets in a pro-inflammatory environment. Interestingly, daily treatment with DS significantly reduces diabetes incidence in pre-diabetic non-obese diabetic (NOD) mice, and most importantly, reverses diabetes in early-onset diabetic NOD mice. DS decreases β-cell death, enhances islet heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG) expression and preserves β-cell mass and plasma insulin in these mice. DS administration also increases the expression of the inhibitory co-stimulatory molecule programmed death-1 (PD-1) in T-cells, reduces interferon-+ CD4+ and CD8+ T-cells and enhances the number of FoxP3+ cells. Collectively, these studies demonstrate that the action of one single molecule, DS, on β-cell protection, extracellular matrix preservation and immunomodulation can reverse diabetes in NOD mice highlighting its therapeutic potential for the treatment of T1D.

Meritxell Morró
May 1, 2020; 69:927-939
Islet Studies

Invitation Only Research Event

Event participants

Jude Webber, Mexico and Central America Correspondent, Financial Times
Michael Stott, Latin America Editor, Financial Times
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

Oversimplification and lack of evidence stigmatise people with mental illness and impede prevention efforts, says Simon Wessley, professor of psychiatry at King's College London, in an editorial published on thebmj.com. Read the full editorial: http://www.bmj.com/content/354/bmj.i4869

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article

Jon Miller is having trouble believing that baseball legend Frank Robinson is gone. Robinson, 83, passed away Thursday morning.