Google parent Alphabet has scrapped its plans to develop a futuristic “Smart City” on the Toronto waterfront over privacy concerns and economic uncertainty brought on by the coronavirus pandemic

John Lafia, who co-wrote the 1988 horror movie "Child's Play" and its 1990 sequel, died on April 29. He was 63.

This trio turned commercial, residential and fashion design experience into the Transition State firm. Next up: a line of throw pillows.

An uneven response from schools is disrupting the lives of students who rely on campuses for education and essential services like food and healthcare.

Highland Park resident Olivia Arthur calls it "art for social distancing — a drive-by gallery for neighbors." The goal: Bring some joy to quarantine.

The L.A. Phil deadline arrives for subscribers to renew for next season, but fans — even loyal ones — say there's too much uncertainty about fall.

Laura Howe repurposed fabric from her Matrushka Construction boutique to make masks for the coronavirus outbreak. She's sold 8,000.

Using chopsticks to stir melted butter and eggs results in a delicious hot breakfast.

This buttery, silky scrambled egg recipe comes together in five minutes and uses chopsticks to make cooking easy.

Read "Attack on Titan," "Somali & the Forest Spirit," "Fire Force," "Arte" and more with Mangamo, a new mobile manga subscription service.

Screening a sample of the population to see who has been infected with COVID-19 and who hasn't is a huge step forward in returning to normal life.

Makeup designer Nicki Ledermann took the concept of the Joker's look from Joaquin Phoenix and Todd Phillips and then made it say everything.

The motion picture academy's new museum should include an exhibit of the painful racist images created to maintain a system of dehumanization.

Greta Gerwig won several prizes for her adaptation of "Little Women." The Oscar was not one of them.

'For tourists coming to Cornwall from Germany, Scandinavia and elsewhere, that's the end,' says Tim Jeans, chairman of Newquay airport

"Tammy's Always Dying" is a low-key, insightful comic drama about a striving woman and her albatross-like mother, played by Felicity Huffman.

Sam Lloyd, known for his role as lawyer Ted Buckland in "Scrubs," died April 30 from complications of lung cancer. He was 56.

HALVING the "arbitrary" two metre social distancing rule would make a huge difference to the economy without jeopardising health, a government pandemic advisor said last night.

AS IT seems that old saying "Cometh the hour, cometh the man" has never been more apt, it's also entirely reasonable to say the world has been extremely poorly served by a raft of groups and organisations that should have been there to help - but that have failed lamentably.

Here are quarantine-friendly ways to get mom a perfect gift for Mother's Day.

The world is nearing 4 million cases of the coronavirus. More COVID-19 news Saturday.

Airport temperature screenings mark latest discord between Trump administration and CDC over federal coronavirus response and science of public health

Take this virus seriously and do your part to protect everyone in the community, a letter to the editors says.

The minority party may change but the rhetoric stays the same

Funding for Trump's border wall is met with resistance

Cidade em que pandemia começou, concentrou o maior número de mortes na China e foi a primeira a impor rigoroso lockdown; habitantes, antes acostumados a apertos e aglomerações, agora vivem outra realidade.

Twelve people were injured by the blaze in a 49-storey residential building in Sharjah.

The past 10 years have shown superheroes in entertainment aren't going anywhere.

The black comics audience should be more demanding after seeing what the HBO series accomplished.

Golden State has had one of the best offenses for the past five years and has done so while slowly moving away from the pick-and-roll.

• A hospital in India is using robots to screen possible coronavirus patients.
• The humanoid robot, called Mitra, uses a handheld thermal camera to evaluate patients before sending them on to healthcare workers.
• Thermal imaging is being tested in other countries as a way to check for coronavirus symptoms. 
• Visit Business Insider's homepage for more stories.

India is yet another country using robots to take some of the burden off of HealthCare workers, with a humanoid robot named Mitra that takes patients' temperatures using a thermal camera.

India's 1.3 billion residents have been under lockdown since March 24, and last week the orders were extended for at least another two weeks. "To save India and every Indian, there will be a total ban on venturing out of your homes," Prime Minister Narendra Modi said. In late April, some convenience stores were allowed to reopen, but specific rules vary by state.

The Indian government has also developed a controversial contact tracing app which shares residents' location constantly. More than 90 million people have reportedly already downloaded the app, and in at least one city, not having the app is punishable with six months in jail.

Meanwhile, these robots are being used in a hospital in Bangalore as the first screening for some patients who may have coronavirus. A pharmacy in Italy has implemented similar technology to screen customers for signs of infection. Here's how they work.

SEE ALSO: Stores in Italy are using robots to screen customers for mask wearing and high temperatures before they can go inside as the country reopens

The robots are a safer way for doctors to perform initial screenings of patients.

A tablet on one robot's chest allows doctors to video chat with patient without putting their own health at risk.

A thermal camera-equipped robot takes a patient's temperature without needing to touch them.

Using this information, healthcare providers can send patients to the appropriate specialist, and patients who are unlikely to have coronavirus won't be unnecessarily exposed.

After receiving a temperature reading, the robot gives the patient instructions for their next steps.

Some experts have suggested that temperature guns are not always accurate because they must be held at a specific distance, but the tablet mostly avoids that problem by instructing patients on where to stand.

Even the most accurate thermometers aren't a perfect measure to stop the virus, though. Infected people can go up to 14 days without showing symptoms, and some people never develop symptoms.

Source: Business Insider

Laine Hardy and Maelyn Jarmon may have won different shows, but their experiences are very similar.

The dinner was the second for the Trump administration.

If you have kids with mobile devices, create a central home charging station in a place like your bedroom. Before the kids go to bed at night, have them put their mobile devices there so they are not tempted to play with them when they should be sleeping.

Digital vs paper: ink on paper may still have the advantage In a recent edition of Scientific American, Ferris Jabr took a look at how technology is affecting the way we read and the differences between reading on screens and …

Improve your understanding of Scrum through the proven experience and collected wisdom of experts around the world. Based on real-life experiences, the 97 essays in this unique book provide a wealth of knowledge and expertise from established practitioners who have dealt with specific problems and challenges with Scrum. You’ll find out more about the rules and roles of this framework, as well as tactics, strategies, specific patterns to use with Scrum, and stories from the trenches.

This script alerts advertisers when regional differences related to the coronavirus have an impact on your PPC campaigns.

Please visit Search Engine Land for the full article.

If you’re an entrepreneur nurturing your own company to a full-blown success, you are always looking for insights and ideas to take your business to the next level, right? But you’re probably super busy as well, and don’t always have the time to figure out where you should be looking for those insights.

The following article, ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion, was first published on 100PercentFedUp.com.

Transcripts of House Intelligence Committee interviews have been cleared for release, and Adam Schiff is reportedly in panic mode. Unfortunately for Schiff, top law enforcement and intel officials said they saw no evidence of collusion between the Trump campaign and Russia in the transcripts. Republicans sought and got approval for the release of the transcripts […]

Continue reading: ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion ...

The following article, Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China”, was first published on 100PercentFedUp.com.

During a recent interview on CNN, Obama-Biden ambassador to China (2014-2017) Max Baucus compared standing up to China on the coronavirus to “Hitler in the ’30s.” Baucus has proven himself to be sympathetic to China in recent interviews, where he puts down America and praises the Chinese. The MSNBC video via The Washington Free Beacon […]

Continue reading: Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China” ...

A beverage company in the U.S. is inviting moms to let out a ‘quaranscream’ this Mother’s Day on a designated ‘zero-judgement venting hotline’ for a chance to win its wine spritzers.

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.

Members Event Screening Room

Event participants

Dr Hamza Al Kateab, Director, AlQudes Hospital, Aleppo (2012-16); Operation Manager, Huozhi
Rita Dayoub, Academy Associate, Centre on Global Health Security, Chatham House; Founder, Health Workers at the Frontline Initiative
Dr Husam Taha El-mugamar, Vice President, Sudan Doctors’ Union UK
Chair: Elham Saudi, Director, Lawyers for Justice in Libya

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.

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.

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.