France is eyeing a lifting of strict coronavirus measures on Monday but for many the damage is done.

The United Nations wants the money to help people in 63 countries, mainly in Africa and Latin America.

The dinner was the second for the Trump administration.

Strong Customer Authentication (SCA) came into effect on September the 14th 2019 as part of the latest General Data Protection Regulation. This new regulation affects many online merchants who sell to those within Europe and other businesses that operate within the region. This regulation was devised to limit the amount of online fraudulent activity and […]

The post Check if Your Stripe Checkout is SCA Compliant appeared first on Tips and Tricks HQ.

We’ve previously taken a look at the notable differences between PayPal and Stripe, although in this tutorial we’ll be focusing on the up and coming Square Payment Gateway and how it compares with Stripe. While both Square and Stripe share some similarities such as their branding and names, they each offer features which suit two […]

The post Stripe vs Square appeared first on Tips and Tricks HQ.

If you run a WordPress website where you intend on adding eCommerce functionality at one stage or another, you cannot go past the free Stripe Payment Plugin. This plugin is designed to allow admin to sell either digital or tangible goods from their website through simple Stripe ‘Buy Now’ buttons. Just like PayPal, Stripe is […]

The post How to Make a Stripe Text Link Payment Button appeared first on Tips and Tricks HQ.

Discover the 10 biggest cruise rip offs that you need to watch out for, and tips on how to avoid or overcome them. There are a number of things that, if you are not careful, you could find you are being ripped off and spending too much on. These are the 10 main rip offs that I have seen and watch out for when I go cruising.

SUPPORT THE CHANNEL BY:
Buying my Cruise T-shirts: http://bit.ly/TFTStore
Booking your next cruise with CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise

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 74 cruises to date.

Follow Tips For Travellers on:
- Instagram: http://www.instagram.com/garybembridge
- Facebook: http://www.facebook.com/tipsfortravellers
- Twitter: http://www.twitter.com/garybembridge

strataconf: Moving to the open healthcare graph http:// http://t.co/YYTUDN3Vzn Achieving the triple aim in healthcare: better, cheaper, safer #stratarx

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.

This week has been a tough one.  It has just become more and more clear that the global travel situation isn’t going to clear up until at least early in the fall.  So while we’re still very hopeful that our Namibia trips starting in September will still happen, we’ve sadly had to cancel or postpone […]

The post Cancelling/Postponing Photography Trips appeared first on Brendan van Son Photography.

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 Amateur Traveler talks to Lee from Atlanta about side trips that you can take when you travel to Shanghai this year for Expo 2010. Lee is currently living in China and talks about 3 different weekend trips to destinations that are located near Shanghai. Lee starts us the in history-rich city of Nanjing the site of “China’s Holocaust” in WW 2. Nanjing has been the capital for 6 different Chinese governments and still retains its ancient walls in addition to modern shopping and the tomb of Sun Yat-sen. It was also the location of the world’s worst civil war, the Taiping Rebellion. After Nanjing we explore the many gardens and the canals of Suzhou. Finally Lee takes us to Hangzhou with its beautiful West Lake which the Chinese compare to heaven.

News

Spirit Air to experiment with carry-on bag fees
Airlines losing 3000 bags – every hour of every day
Women try to smuggle dead relative onto flight
Paying to use the plane potty?
Ky. Judge Rules in Favor of Online Travel Sites

Show Notes

Expo 2010 Shanghai China
Travel to Shanghai, China – Episode 26

Nanjing
Nanjing, China
Nanking Massacre
John Rabe – a German businessman and Nazi party member who is best known for his efforts to stop the atrocities of the Japanese army during the Nanking Occupation
Sun Yat-sen – “Father of the Chinese Nation”
Ming Dynasty
Cheongsam or Qipao – traditional Chinese dress
Taiping Rebellion – largest civil war in history started by Hong Xiuquan who declared himself the brother of Jesus.

Restaurants
Skyway Bakery and Deli
Les 5 Sens
Tairyo Teppanyaki

Suzhou
Gardens – Master of the Nets, Lion’s Forest, Humble Administrator
Mingtown Suzhou International Youth Hostel

Hangzhou
Tea Museum
A History of Chinese in California
Braised Pork Belly – Hangzhou Dongpo Pork
Sweet and Sour Pork Recipe
Wushanyi International Youth Hostel

Shanghai
Captain Youth Hostel

elong.com, ctrip.com – for accompodations

Community

Egypt Photo Tour
Amateur Traveler Newsletter
Does Amateur Traveler work for you at work?

The Amateur Traveler talks to Italophile Ira Bernstein who returns to the show to talk about day trips in Tuscany that you can take from Florence. We talk about visiting the walled city of Siena and its famous bareback horse race the palio, viewing the many towers of San Gimignano, climbing the leaning tower of Pisa (after you take the obligatory picture of someone holding it up), and walking on the walls of Lucca. Each town has its own character and attractions. Arezzo has a jewelry museum and the home of the “Father of Humanism” Petrarch. Fiesole is a rich enclave, a suburb of Florence with views of the city and a roman theatre. Montepulciano and Montalcino are both known for their wines. Ira talks about some of the events that the locals enjoy like the palios, flea markets and flag throwing competitions. So even if you just get as far out of Florence as Piazzale Michelangelo there are many places to explore in Tuscany.

The Amateur Traveler talks to Kirk Horsted in a two part episode on the Twin Cities of Minneapolis and Saint Paul, Minnesota. In this second half Kirk looks at the state capital of Saint Paul, Minnesota.

Hear about a road trip around Ontario as the Amateur Traveler talks to guidebook author Carolyn Heller, author of the Moon guide to Ontario. 

In preparation for the 2017 500th anniversary of the Reformation, Chris (the Amateur Traveler) took a road trip through "Luther Land" and the heart of Germany.

Hear about travel to 4 national parks in British Columbia as the Amateur Traveler talks to Carolyn B. Heller author of "Moon Vancouver & Canadian Rockies Road Trip".

Hear about a road trip in Central Mexico as the Amateur Traveler talks to Amie from thetravelingtogetherjournal.com about a trip they took near Mexico City.

Hear about travel to Southern New Brunswick as the Amateur Traveler talks to Kirsten Maxwell from kidsareatrip.com about her recent travel to the Province with her family.

Hear about a Route 66 road trip as the Amateur Traveler talks to Austin Coop from 2laneamerica.com and guidedroute66tours.com about the Mother Road.

Hear about a road trip in Kansas as the Amateur Traveler talks to John McKenzie of johnthetraveler.com about the state of his birth. 

Hear about an Oregon Coast road trip as the Amateur Traveler talks to Jessica Baker from BoundlessBakers.com about a portion of their year and a half long road trip.

After spending two months living in Mérida and years of trips traveling through the Yucatán Peninsula, I’ve finally put together the best itinerary for two weeks in Mexico. Most travelers go to Mexico to lie on the beach for a week, maybe go on an excursion to a ruin or a cenote, and head straight …

Two Weeks in Mexico: The BEST Yucatán Road Trip Itinerary Read More »

The post Two Weeks in Mexico: The BEST Yucatán Road Trip Itinerary appeared first on Adventurous Kate.

With a bright, 8.2-inch HD display and the flexibility to work in almost any vehicle, the Lanmodo Automotive Vast Night Vision System is a near-perfect alternative to factory-installed systems.

The post Brighten Up Your After-Dark Road-Tripping with Lanmodo’s Vast Automotive Night Vision System appeared first on Vagabondish.

The DML News App offers the best in news reporting.

The post REPORT: Obama rips Trump over coronavirus in private call appeared first on Dennis Michael Lynch.

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 ...

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.

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.

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.

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.

5 June 2014 , Volume 70, Number 3

The Golan Heights is home to thousands of Druze who cling on tenaciously while looking over their shoulder at the chaos in their homeland

HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions.

Site-specific arrest of RNA polymerases (RNAPs) is fundamental to several technologies that assess RNA structure and function. Current in vitro transcription “roadblocking” approaches inhibit transcription elongation by blocking RNAP with a protein bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires inclusion of a protein factor extrinsic to the minimal in vitro transcription reaction. In this work, we developed a chemical approach for halting transcription by Escherichia coli RNAP. We first established a sequence-independent method for site-specific incorporation of chemical lesions into dsDNA templates by sequential PCR and translesion synthesis. We then show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification or 1,N6-etheno-2'-deoxyadenosine base efficiently and stably halts Escherichia coli RNAP transcription. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables display of nascent RNA molecules from RNAP in a minimal in vitro transcription reaction.

Invisibility is no longer confined to fiction. In a recent experiment, microwaves were bent around a cylinder and returned to their original trajectories, rendering the cylinder almost invisible at those wavelengths. This doesn't mean that we're ready for invisible humans (or spaceships), but by using Maxwell's equations, which are partial differential equations fundamental to electromagnetics, mathematicians have demonstrated that in some simple cases not seeing is believing, too. Part of this successful demonstration of invisibility is due to metamaterials electromagnetic materials that can be made to have highly unusual properties. Another ingredient is a mathematical transformation that stretches a point into a ball, "cloaking" whatever is inside. This transformation was discovered while researchers were pondering how a tumor could escape detection. Their attempts to improve visibility eventually led to the development of equations for invisibility. A more recent transformation creates an optical "wormhole," which tricks electromagnetic waves into behaving as if the topology of space has changed. We'll finish with this: For More Information: Metamaterial Electromagnetic Cloak at Microwave Frequencies, D. Schurig et al, Science, November 10, 2006.

Researcher: Sidney Redner, Santa Fe Institute
Moment: Moment Title: Holding the Lead Description: Sidney Redner talks about how random walks relate to leads in basketball.

Researcher: Norbert Stoop, MIT
Title: Adding a New Wrinkle
Description: Norbert Stoop talks about new research on the formation of wrinkles.