How to get a second passport in the Caribbean – Business Insider – Business Insider

At the beginning of 2020, the US passport enjoyed a relatively high ranking on the Henley Passport Index, an annual report that ranks the strength of passports based on how many countries it grants holders visa-free access to. A person with US citizenship could gain visa-free access to 185 countries.

The coronavirus pandemic has changed that. Now, the US passport is rapidly losing some of its status. In July, CNN reported that the US passport is about as powerful as the Mexican one, which is currently ranked 25th in the world and allows visa-free entry to 159 countries.

For US citizens looking to explore secondary passport options, Caribbean countries present an appealing opportunity. Of the 13 Caribbean countries, it's possible to obtain citizenship for the cost of $150,000 or less in five of them: St. Kitts and Nevis, St. Lucia, Dominica, Grenada, and Antigua & Barbuda.

The Dominican Republic offers the next-most-affordable option for people seeking second passports; permanent resident status there can be obtained through an investment of $200,000 in a local business.

For comparison, as of November 2019,obtaining an EB-5 immigration visa to the US could set you back by about $1.8 million.

Jennifer Malin, an attorney and citizenship-by-investment expert based in St. Kitts and Nevis, told Business Insider that since the beginning of the pandemic, she has seen has an increase in interest from US citizens exploring second citizenship options.

"There's recently been an increase in applicants that are applying, particularly because they lowered the price for a family of four, and many of the citizenship programs have made changes to their programs that are more beneficial to applicants," Malin told Business Insider. The amount was reduced to $150,000 from almost $200,000 in July 2020.

Paddy Blewer, Public Relations Director with Henley & Partners, told Business Insider that one of the first steps in obtaining a passport via a citizenship-by-investment program in the Caribbean is proving that you have the capital to make that investment. Applicants will also have to go through a rigorous background check.

The result, Blewer said, is that applicants tend to be wealthy.

"Almost certainly the people that acquire alternative citizenship are quite wealthy because you're talking about having at least just over a hundred thousand us dollars to make this investment, at the very least," Brewer said. "The reality is, is it may well be more because it won't necessarily just be for you. So it very quickly racks up into early six figures."

The whole process takes two to three months.

Citizenship by investment is not the only way to get a second passport, however. You can also become a citizen through descent, marriage, and naturalization.

Here's everything you need to know if you're thinking of getting second citizenship in St. Kitts and Nevis, St. Lucia, Dominica, Grenada, and Antigua & Barbuda. Note that the US and each of these five Caribbean countries allows dual citizenship, which means you do not have to give up the passport of one country in order to become a citizen of the other.

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Havana, the ‘Paris of the Caribbean,’ gets its own Eiffel Tower – Reuters

HAVANA (Reuters) - Havana was once dubbed the Paris of the Caribbean for its beautiful architecture, vibrant arts scene, and flourishing nightlife. Now it even has its own Eiffel Tower.

Jorge Enrique Salgado explains how he built a replica of the Eiffel Tower on the roof of his home in Havana, Cuba, August 6, 2020. Picture taken August 6, 2020. REUTERS/Alexandre Meneghini

The illuminated four-meter (13-ft) high replica by Cuban blacksmith Jorge Enrique Salgado lights up a corner of the otherwise dimly-lit Arroyo Naranjo southern residential district of the capital.

Salgado, 52, an accountant who learnt metalworking from his father, says he has never been to Paris. But he had seen the Eiffel Tower in films and photos and when his son asked him to make an antenna to capture the Wi-Fi signal of a nearby park, he hit on the idea of making a model.

Home internet service is not widely available in the Communist-run island, but Wi-Fi hotspots have been rolled out in parks and plazas nationwide since 2015.

In the end, the project took on a life of its own and they never installed the antenna because they felt it would ruin the aesthetic of the model that took months to build. Cuba has also rolled out mobile internet over the last year and a half.

To make the tower, my son downloaded plans, models, photos and other details via the internet, said Salgado. I realized the original tower was built piece by piece so thats what I did.

Salgado said he bought and salvaged pieces of iron railings to built the tower on the roof of his home, using car halogens to light it up, in a country where it is often difficult to find material.

We based our lighting exactly on the original, said his son, Enrique Salgado, who helped him build the replica.

The enthusiasm in the neighborhood for his Eiffel Tower has kindled hopes he could make a living from the passion project and he is now working on a slightly smaller model to sell.

I never thought of dedicating myself to this, never, said Salgado. (But) it would be an honor to be able to live off this.

Reporting by Reuters TV; Writing by Sarah Marsh; Editing by Rosalba O'Brien

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Latin America & The Caribbean – Monthly Situation Snapshot – As of 6 August 2020 – World – ReliefWeb

LATIN AMERICA & THE CARIBBEAN: COVID-19 CRISIS OVERVIEW

Latin America and the Caribbean now accounts for nearly 30 per cent of global COVID-19 cases, despite having less than a tenth of the global population. The severity of the pandemic is threatening hard-won gains made in the last ten years and creating critical multidimensional humanitarian needs. Middle- and highincome countries that do not traditionally receive multilateral assistance are requesting support, as many of their citizens are now turning to government help to survive. The situation is likely to worsen as countries re-open to mitigate the economic downturn amid strained healthcare systems.

5.1MCONFIRMED CASES OF COVID-19 AS OF 5 AUGUST

8KCASES PER EVERY 1 MILLION INHABITANTS AS OF 5 AUGUST

ECONOMIC PROJECTIONS

Projections from the UN Economic Commission for Latin America and the Caribbean (ECLAC) indicate that the COVID-19 crisis will trigger a 9.1 per cent contraction in regional GDP, the region's worst recession in a century, potentially causing 45 million more people to fall into poverty and 28 million more people to fall into extreme poverty by the end of 2020. This projected impact stands to put millions of people at risk of undernutrition.

FOOD INSECURITY

The COVID-19 crisis is exacerbating existing food insecurity, particularly for people in Central America dealing with recurring climate shocks and in people in Haiti with limited food access due to pre-pandemic mobility restrictions. WFP estimates some 16 million people with acute food insecurity in 2020, up 269 per cent from 4.3 million people in 2019 and the highest relative increase in the world.

VULNERABLE POPULATIONS

Women are suffering exacerbated social and economic gaps that have reduced economic resilience and increased care demands at home, where they are more exposed to violence during confinement.

113WOMEN IN POVERTY FOR EVERY 100 MEN

50%+MORE GBV REPORTED IN SOME COUNTRIES

Many indigenous peoples live in remote areas with poor access to quality healthcare and information, prompting growing calls to address health response gaps, especially in the Amazon region.

49K+CASES REPORTED IN INDIGENOUS GROUPS IN THE REGION (6 JULY)

170KINDIGENOUS PEOPLE IN BRAZIL-COLOMBIAPERU AMAZON AREA

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Latin America & The Caribbean - Monthly Situation Snapshot - As of 6 August 2020 - World - ReliefWeb

June, A Month of Many Celebrations: Caribbean Heritage and LGBTQIA+ Pride (Opinion) – Skidmore News

*Trigger warning: Some mention of violence towards gay men.

June has become a celebratory month for both LGBTQIA+ Pride and Caribbean-American Heritage. This year, the annual NYC Pride Parade and several Caribbean awareness organizations had to cancel their events due to the impacts of the Coronavirus. Despite the cancellation of many major parades, both communities have found ways to celebrate themselves during the month of June. As many people across the nation continue to march for Black Lives, recently, a spectrum of identities within the LGBT+ Caribbean community have come into view, and it is important to acknowledge how these communities clash.

One of the many taboos in the Caribbean is having open discussions about the LGBT+ community. West Indian families are very much silent about the topic and express their homophobia, transphobia, and heteronormative feelings about different sexualities in ways that can be marginalizing. Often, West Indian communities condemn their own family members, calling them derogatory names, and these individuals are usually unable to feel truly welcomed in public spaces. West Indian people are also in denial of their stigmatizing of the LGBT+ community, where verbal and physical abuse, as well as discrimination of one's sexuality is pertinent in the culture. Many are pressured to conform to the subjective representations of "masculinity" or "femininity" because of religious and cultural expectations. This creates a complete dismissal of transgender, transsexual, bisexual, queer and intersex persons, whose different gender and sexuality identities are confronted by heteronormative beliefs of West Indians.

One of the many reasons Caribbeans celebrate their heritage is because of the wide range of music across cultures. Caribbean music is fundamental to how people survive, work, and feel liberated on the day-to-day. West Indian culture is highly appreciated for its Dancehall music. For many Caribbean countries, Dancehall has become economically central, with people using the genre to create new fashion styles, events, and dance forms. However, it is also a genre that promotes extremely homophobic lyrics. Our most beloved Dancehall artists, such as Beenie Man, Elephant Man, Sizzla and Vybz Kartel have all been lyricists for the burning, drowning, and violence against gay men. The notorious 1988 song by Buju Banton, "Boom Bye Bye" advocates for the brutal shooting of a gay man in the head in its lyrics.

Many Eastern Caribbean countries continue to enact discriminatory laws against LGBT+ people. Countries such as Antigua & Barbuda, Barbados, Dominica, Grenada, St. Kitts & St. Nevis, St. Vincent, the Grenadines, and St. Lucia have had several reports of discriminatory legislation called "buggery laws,'' that negatively impact the LGBT+ population. Laws implemented were originally fostered by British colonialists, prohibiting consensual same-sex marriages and public relationships. Even so, West Indian culture has traditionally always been ingrained with heteronormativity. Law enforcement tends to dismiss harassment and sexual violent cases, often asking people if they are "straight" first before helping them.

The clash between Caribbean cultures and LGBT+ communities have created a segway for Caribbean organizations to step forth and diminish the stigma and violence against people. Non-profit organizations such as The Caribbean Equality Project (CEP), located in Queens, NY have empowered the voices of LGBT+ people of Caribbean origin. CEP was founded by Mohamed Q. Amin, who is an Indo-Caribbean Guyana native and gay rights activist. After a troubling violent hate crime shook the queer community in Richmond Hill, Queens, he created CEP to bring hope and to advocate for the inclusion and equality for all West Indian gay, lesbian, bisexual, transgender, and queer+ people in NYC. CEP has worked to equalize spaces for queer people to receive medical, food, immigration, and mental health resources through several GoFundMe pages and services. Also, their organization has expanded, receiving recognition from Dominique Jackson of the popular Netflix show POSE, who spoke in their storytelling campaign series, "My Truth, My Story" that documents stories of LGBT+ people from the Caribbean. The storytelling series goals are to liberate and unshackle survivors from living in silence and fear, while providing a space for them to speak their own truths and educate others within the Caribbean diaspora.

The first Pride Parade occurred in 1970 in New York City, and was often recognized as the initial stage of the LGBT+ rights movement. This year, we celebrated the 50th anniversary of Pride and despite the political climate of our nation, a united community of people walked together with their masks on, safely advocating for Black lives and Queer liberation. CEP partnered with API Rainbow Parents, GAPIMNY, Barkada NYC, Sige!, and Q-Wave and joined hands with them to celebrate LGBT+ people and give recognition to people of Caribbean heritage and other cultural backgrounds.

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June, A Month of Many Celebrations: Caribbean Heritage and LGBTQIA+ Pride (Opinion) - Skidmore News

Pirates Of The Caribbean 6: 5 Things We’d Want In A New Movie (& 5 That We Don’t) – Screen Rant

Pirates of the Caribbeanhas truly stood the test of time. With five movies under its belt and two more on the way, there are plenty of stories to be told. One of those movies will be a continuation of the current series while another will star Margot Robbie in a female-fronted reboot.

RELATED:Pirates Of The Caribbean: 5 Things The Reboot Can Improve (& 5 Ways It Can Fail)

Fans have high expectations when it comes to these movies sincePirates of the Caribbeanis still one of the most beloved movie franchises out there today. However, it hasn't necessarily gotten better through its run. Viewers are definitely looking for some particulars in the next sequel and spin-off.

Fans asked and they shall receive: Margot Robbie is going to star in the reboot, which will not be connected to the main storyline. It's about time that a female pirate lead steps into the spotlight in a franchise that hasn't had too many women characters before.

There's also no reason that the sequel movie can't focus on a female character, pirate or otherwise, especially with some options available. Carina, Barbossa's daughter, or perhaps even Elizabeth (the Pirate King herself!) couldreturn after her brief cameo in the fifth movie.

Many fans are not clamoring for the return of Captain Jack. He has certainly run his course, having starred in all five movies. The character has really gone downhill over time. While he started the series as a smart man who was ten steps ahead of everyone around him, he descended into a drunken pirate who was barely along for the ride.

RELATED:Pirates Of The Caribbean: 5 Ways To Reboot The Franchise (& 5 Reasons It Should Be Left Alone)

There are plenty of other leads that can take his place, the most obvious being Will, who is poised to command the sixth movie with a resurrected conflict against Davy Jones. When it comes to Jack,audiencesmay have simply had their fill of the captain.

Pirates of the Caribbeanis iconic for a reason, as it knew how to write memorable characters. With Jack (the captain and the monkey), Pintel, Ragetti, Barbossa, Will, Elizabeth, Tia Dalma, and many more leading the way,lovable characters abound, even when they'retechnically bad news.

Both new movies have the opportunity to create new characters, whether they're comedic relief or serious members of the crew. It would be refreshing after all these years to fall in love with a new crew of pirates or even some fresh bad guys.

Technically,Pirates of the Caribbeanbegan asa dark story. It had cursed skeletons, wayward pirates, and plenty of gray skies on the sea. But the movies only got darker and darker. A lighthearted take (with a visually pleasing aesthetic) would serve to revive the tired franchise.

When Margot Robbie's crew sets sail, that would be the best chance to see a totally fresh take on the pirate world. Here's hoping that she can do for pirates what she did for Harley Quinn and have some fun on screen. Hopefully, the sixth film willalso be a bit lighter.

Many longtime viewers are already fan-casting who would be the best additions to the series, with names ranging from Karen Gillan to Florence Pugh. If there's one thingPirates of the Caribbeanhas always been good at, it's all-star celeb cameos for the best roles.

Whether it's Javier Bardem as a villainous captain or Bill Nighy as the legendary Davy Jones,the franchise didn't pull punches when it came to casting. The new movies have the potential to add more exciting names to a long list of hits.

Viewers have gotten attached to the central characters who make upPirates of the Caribbean,especially the original trifecta of Jack, Will, and Elizabeth. It would simply be painful to watch them get unhappy endings after all these years.

RELATED:Pirates of the Caribbean: 5 Characters Who Got Fitting Endings (& 5 Who Deserved More)

Since Will is poised to star in the next sequel now that Davy Jones has possibly returned, it would be terrible to watch the former meet an untimely demise or get cursed again. He already got a happy ending, being reunited with Elizabeth and Henry, so the next movie should not resort to forced drama.

Many talented actors and fantastic characters have contributed to the series over the years, but the cast has not always been the most inclusive. Zoe Saldana made a splash in the first movie as Anamaria and no one could forget Naomie Harris's turn as Tia Dalma, but the franchise needs to create moreopportunities for diversity.

There are so many phenomenal actors of color who could seamlessly join the sixth film's cast, and the same can be said for the spin-off. Fans can't wait to see who gets cast next.

It's not exactly a secret thatPirates of the Caribbeanmovies became long, convoluted, and way too wacky. With so many supernatural and fantastical elements, it was easy for the series to go overboard.The next movies need to rein it in and bring back the excitement ofThe Curse of the Black Pearl's action-adventure status.

The spin-off has the potential to put together a straightforward and acclaimed movie about female pirates on the open sea, while the mainline sequel should stick to what the series does best: Character-driven adventures. Although Davy Jones was supernatural, it was really when they began adding too many villains andplot threads that the franchise crossed a line.

Pirates of the Caribbeanhas never taken itself too seriously and the actors seemed to have plenty of fun on set. While they cast many popular actors in major roles, they also brought on some fan favorites in cameos. Namely, Keith Richards and Paul McCartney stood out as Jack's family members.

RELATED:Pirates Of The Caribbean: 5 Best Rivalries (& 5 That Make No Sense)

It was a fun nod to Jack's rock-star roots and inspiration, and the new movies should keep the gag going. These cameos never got in the way of the movie, so it would be a nice touch to see who stopped by the set for a day of dress-up.

The Curse of the Black Pearlfeltlike it could have been made in the Golden Age of Hollywood. The swashbuckling spectacle had the perfect mix of practical and special effects.

The movie magic was just that magical. But the movies went on to feature more and more CGI, until they transformed into indistinguishable blockbusters. The next movies should go back to the roots of the first one, taking care to portray the setting as realistically as possible while toning down the over-the-top effects or story beats.

NEXT:Pirates Of The Caribbean Reboot: 5 Actresses We Want To Join Margot Robbie (& 5 We Don't)

Next 10 Movie Flops That Shouldve Been Hits

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Pirates Of The Caribbean 6: 5 Things We'd Want In A New Movie (& 5 That We Don't) - Screen Rant

Pirates of the Caribbean: News, reviews, and how to watch the movies – Polygon

Avast ye, landlubbers here be pirates.

Disneys Pirates of the Caribbean movies were a gamble (a movie based on a theme park ride?) on top of a gamble (a pirate movie in the year 2003, really?) on top of a gamble (Johnny Depp doing a Keith Richards impression?) that became a worldwide sensation and defined the mid-2000s. The Curse of the Black Pearl was soon followed by back-to-back entries with Dead Mans Chest and At Worlds End. The iconic characters, the rich mythos, the sweeping score, and the swashbuckling sword fights grabbed audiences by the rigging back then and never quite let go.

I guess you could say weve chosen the pirates life.

While the fourth and fifth films, 2011s On Stranger Tides and 2017s Dead Men Tell No Tales, sizzled out stateside, they still brought in that box office booty around the world, meaning that the Pirates of the Caribbean franchise is far from the depths of Davy Jones Locker. Based on reports from this year, a direct Pirates 6 sequel is in the works, and newly revealed side-quel starring Margot Robbie on the horizon. WIth all the good movies now on Disney Plus now (and without much else in theaters), this was the perfect time to, take the helm and set sail to plunder the rich expanse of this franchise.

What treasures shall we find in these pirate-infested waters? Grab your cutlass, hoist the colors, and lets find out.

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Pirates of the Caribbean: News, reviews, and how to watch the movies - Polygon

What a Year Without Caribbean Carnival Means for the Region – Cond Nast Traveler

With no end to the COVID-19 pandemic in sight, the current climate is impacting revenue well into the future. Haitian American Carl Napoleon, CEO and founder of Carnival Jumpers, says that even though governments have not announced final decisions on 2021 events, many of his clients have decided not to risk it. People have already begun canceling bookings for 2021. Theyre sad about not celebrating with their friends, but COVID has them leery about going anywhere, let alone a large event like Carnival.

Out of necessity, the industry has already begun rethinking what Carnival will look like down to roadand how to keep the spirit alive. Despite the obvious losses, many see the Caribbeans tenacity shining through. Kelvin Jacob, CEO of the Grenada Spicemas Corporation (which runs a festival of the same name), sees virtual experiences as an opportunity.

Grenada has become innovative in its quest to keep the excitement about Carnival sustained into 2021, with virtual events throughout the festival period," says Jacob. The events have already begun with live virtual Carnival City shows held every Thursday via YouTube and Facebook, showcasing local artists and their music, to culminate in a virtual Grand Concert on August 9.

For others, COVID-19 has been a reason to turn inwardand reconsider who Carnival is really for. Jules Sobion, CEO of Caesars Army and creative director of Rogue Mas, is thinking about a Carnival thats solely about the people of Trinidad and Tobago.

Our Carnival is a very sensory product, so I think its difficult to apply social distancing measures, especially on the road or in the ftes," says Sobion. "My vision for Trinidad and Tobago Carnival in 2021 would be totally localwith the borders closed, unless a vaccine is foundwhich will give the country the opportunity to rethink, re-strategize, and repackage our holistic cultural product.

Missing Carnival has ultimately left many, like Trinidadian blogger Marissa Charles, founder of Global Carnivalist, reminiscing on how much of the experience they once took for granted. I feel like there are certain aspects of Caribbean culture that I took for granted and appreciate much more now," she says. "I genuinely miss the freedom of a Carnival parade, being in a crowd without feeling paranoid about COVID, and the sense of community that Caribbean culture provides. Being unable to celebrate ourselves month after month has been devastating.

Even without a physical presence, the message of Carnival is still clear: The Caribbeans greatest strength is in its unity. It is this togetherness, and commitment to tradition, that Sobion feels will get islands through this challenge. This is a time for metamorphosis for the entire industry and all of its stakeholders. Lets all come together and use this pandemic as the proverbial cocoon, in which we will transform from our old way of life and emerge into something new and beautiful for the entire world to see.

We're reporting on how COVID-19 impacts travel on a daily basis. Find all of our coronavirus coverage and travel resources here.

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What a Year Without Caribbean Carnival Means for the Region - Cond Nast Traveler

Pirates Of The Caribbean: 10 Things Everyone Missed About Jack Sparrow – Screen Rant

When it comes to characters in films, the list can go on and on for whose the best and who's everyone's favorite. Out of every list and every possibility however, there's one thing most people can agree on: No one is quite like Captain Jack Sparrow.

RELATED: Which Pirates Of The Caribbean Character Are You Based On Your Zodiac?

Ever since Johnny Depp graced the world with Sparrow inCurse Of The Black Pearl, he's become a household name, with many fans loving his character. Yet, despite loving Sparrow, there are many facts and details about him that people tend to forget happened. Here are 10 things everyone missed about Captain Jack Sparrow.

Although it's somewhat of a well-known fact, many audience members do tend to miss or forget that Jack Sparrow was marooned. Given Barbosa's mutiny, it's not surprising Jack was strandedand yet it's there'ssomething else people overlook.

When they see Jack Sparrow, they think of a cool, collected hero who can almost always overcome any obstacle thrown his way. Yet, when Jack was stranded, he relied on rum runners instead of himself for rescue, perhaps showcasing his true nature. Not as a legendary pirate but a lucky man.

Throughout many films, there are little bits that are seen as running jokes, where either the main character or someone close to them keeps running into trouble that's seen as a bit. For Jack Sparrow, one of his running bits is a key detail that many overlook.

During the series, Jack always has a compass with him that never points north, making many assume that it's broken. Thecompass is in fact magic to some extent and instead points towards what Jack desires the most, making for a handy tool.

Many words jump into people's heads when thinking of Jack Sparrow. They range from the world's greatest pirate to a drunken buffoon and yet one word that's never included ishero. In some cases, Jack is the unlikeliest of heroes despite being a pirate.

RELATED: 10 Best Quotes From The Pirates Of The Caribbean Movies

In a deleted scene fromAtWorlds End, it's revealed that Jack was hired by Beckett, one of the film's villains, to deliver a shipment of slaves. However, Jack chose to free the slaves, leaving him branded with the mark of a pirate despite his heroics.

The notion of Jack Sparrow, a drunken yet likable and clever buffoon, could be a great captain is a ridiculous idea that would make any fan chuckle... despite it being true. Before Jack lost the Black Pearl to Barbosa and became seen as an outcast, he was a great captain.

Truth be told, audiencesnever hear of his legendary tales, and yet, throughout the films, movie-goers watch him navigate his way around even the leakiest of ships with ease as if he knows it like the back of his hand.

Everyone remembers the first time they saw Captain Jack Sparrow make his grand entrance on the big screen and recall his tale of how he lost the Black Pearl to his mutinous first mate, Barbosa. However, some fans tend to forget that Jack didn't just lose the Black Pearl once. He lost it twice.

At the end of the original Pirates trilogy, Jack returns to port, hoping to set sail on his newly reclaimed ship... only to watch it sail off into the distance with Barbosa at the helm.

There are many reasons why fans don't remember details and informationabout the fourth Pirates film,On Stranger Tides.For manyfans, it wasn't the strongest, especially after the original trilogy, and the ideaof Jack and the daughter being a couplewas a minor note.

RELATED: Pirates Of The Caribbean: The Worst Thing About Each Main Character, Ranked

That being said, it's an odd noteandfeelsstrange to hear that Jack and Blackbeard's daughter were in love. Yet, when you look at her and then back at Jack, it makes a little sense as to why they were attracted.

In just about every movie no matter the genre, there's always a deal to be made with some kind of devil. Whether the devil comes in human form or that of a humanoid squid pirate, the results are still the same as Jack Sparrow discovered.

Even though it's a key plot point for most ofDead Man's Chest, Jack making a deal with Davey Jones for the Black Pearl is something many fans and audience members either miss or fail to remember.

As the old saying goes, "opposites tend to attract" and there's nothing more opposite than Jack Sparrow and Joshamee Gibbs. A pirate and a British sailor should and do have nothing in common or at least in most cases, they shouldn't.

Over the course of five films, however, the friendship between Jack and Gibbs goes largely unexplained, with the pair either having each other back while also trying to stab it as most friends do. It almost makes one wish for a spinoff centered around the duo's unlikely friendship.

It goes without saying that the universe ofPirates Of The Caribbean is one of the more bizarre andfascinating ones, full of historical tidbits mixed in with loads of myths, legends, and supernatural occurrences that plagued the seven seas.

RELATED: 10 Things That Make No Sense About Pirates Of The Caribbean

As it stands, Jack has gone up against numerous supernatural creatures and survived. From the goddess Calypso to a curse that makes the bearers skeletons to Davey Jones himself to mermaids and even ghosts, Jack has seen more than enough of both the real and supernatural sides of Pirates.

The true backstory of Captain Jack Sparrow will remain a mystery for a great number of fans and movie-goers and yet there's one fact that can be proven, the fact that Jack Sparrow has and always will be a pirate.

Since he was a sailor and took command following the dreaded Captain Salazar's attack, Jack has always been the pirate that fans love. While over the years his luck and lifemay have fallen on hard times, Jack willforever be the greatest pirate anyone's ever seen.

NEXT: 5 Reasons The New Pirates Of The Caribbean Reboot Will Work (& 5 Why It Won't)

Next 5 Most Underrated Animated Movies (& 5 Most Overrated)

Drew Atchison is a writer, reader, and avid movie goer based in Phoenix, Arizona. He's gone from being a line cook to a trading post employee to an actual zip line attendant and now a list writer for screen rant. Currently enrolled as a film production major at Azusa Pacific University.

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Pirates Of The Caribbean: 10 Things Everyone Missed About Jack Sparrow - Screen Rant

The Pirates of the Caribbean cast: who was the best love interest? – Polygon

With the Pirates of the Caribbean movies more accessible than ever, and a summer season void of blockbusters, this month were diving deep into Disneys swashbuckling series. Grab your cutlass and hoist the colors: here be Polygons take on all things PotC.

The Pirates of the Caribbean franchise juggles a lot of balls, but perhaps one of the most gripping threads is romance. Throughout the original trilogy, Elizabeth Swann is the central point of a triangle formed by Will Turner, Jack Sparrow, and James Norrington. The films end with Elizabeth choosing Will but was he the right choice?

To discuss the pivotal romance in the original Pirates trilogy, three Polygon staffers Karen Han, Emily Heller, and Petrana Radulovic convened to talk over Elizabeths three potential beaus, as well as all of the other high-seas heartthrobs introduced throughout the series.

Karen: Id like to start with the Big Three: Will, Jack, and Norrington. You guys have told me before that you both love Will why is that?

Emily: I do love Will Turner. I love a boy who pines.

Karen: So there was never any competition?

Emily: No, and in fact, I was annoyed whenever Jack Sparrow would get flirty with Elizabeth, and whenever anyone I talked to was into Jack Sparrow. I was anti-Jack Sparrow.

Petrana: I did not like Jack in the way a lot of people I know did. I do love a charming rogue, and as an audience surrogate crush, I get it, but I never wanted him for Elizabeth.

Karen: Please expand on why you love Will so much.

Petrana: I think Orlando Bloom is very cute. I think that was 85% of it, especially when I watched those movies. I also like a good childhood best friend love story, and I liked that it was mutual. They were both into each other, and society didnt like it, but they decided, hey, fuck society.

Emily: For me, I love a loyal character who has a moral code that they stick to even when theyre teaming up with someone who is not necessarily sticking to that. Whats interesting is that I was not an Orlando Bloom gal, I was not into Legolas. I was into Sam, that was my guy. Its that sort of loyalty that I really dig.

Petrana: I do like that Will has these principles. Norrington is the other character who has a strict moral code, in contrast to Jack, but his is a code of honor, which is hot in its own right. Whereas Wills devotion is to the people he loves.

Karen: The next logical talking point is Norrington, because he is the third love interest, but I feel like hes someone no one really considered until his arc in the second and third movies.

Petrana: I actually saw the movies in reverse order. I wasnt allowed to watch them because they were scary, so I saw the third one with my friends when I was old enough, then I saw the second one with my cousin. I finally saw the first one because I told my parents I was really into those movies. I think seeing them in reverse really elevates Norringtons story. He sacrifices himself for Elizabeth, and he was really hot in the second one. But then you watch the first one and its weird that she knew him when she was 11 and he was, like, 25.

Emily: I did not think of Norrington as anything other than an obstacle between Elizabeth and Will in the first movie. I agree that he was hot in the second and third movies. Removing that powdered wig really helped him out there.

Karen: So in the second and third movies, were you no longer like, Get him out of here, Will and Elizabeth need to kiss, because it was clear that Will and Elizabeth would get together?

Emily: I think because it was clear that Norrington did not have a chance with Elizabeth, that she was in love with Will and it was great, I did not see him as a threat then, and he was allowed to be cute without being a hindrance. The second movie is actually where I got really mad about the Jack Sparrow stuff, because thats where Elizabeth kisses him, and the look on Wills face when he sees it happen is devastating, because he doesnt know why shes doing it!

Petrana: The kiss is for the greater good! She kisses him for Will! Its the only way to save all of their asses. But he doesnt know that, so its dramatique.

Karen: So both of you, from the beginning, were like, She should be with Will Turner, there is no alternative, this is who she should choose. I will say I havent found Orlando Bloom attractive until very recently starting from when he was a villain in the Three Musketeers movie. I wasnt in love with Will while watching these movies. But I wasnt in love with Jack Sparrow, either. I was more interested in Norrington because of his redemptive arc; thats the story trope that really works for me. I find it interesting that both of you were with Will Turner from the beginning, because I feel like so much of the fandom thinks she shouldve gotten with Jack Sparrow.

Petrana: The fact that her choice is very clear from the beginning makes the other men good for the audience to project upon. Jack doesnt have a love interest until Penlope Cruz in the fourth movie (which doesnt count).

Emily: I never really went for the bad boy thing, I remember I got really mad at my sister for being really into the Phantom of the Opera. Thats part of why I wasnt into Jack Sparrow. If I was going to go for a bad boy, I would be into a bad man, i.e. Captain Barbossa.

Petrana: I have to wonder what it is specifically about Jack that I didnt get, because I usually do go for the rogue. I think the key thing missing is the heart of gold. Jack doesnt really have it. Hes an interesting character, but lacks the ride-or-die appeal of Will.

Karen: Yeah, the interesting thing about the end of the second movie is that hes trying to make an ultimately selfish and very villainous choice. So, of the three main love interests, the consensus is, two out of three, that Elizabeth made the right choice. But who would you pick?

Petrana: Will, but if Norrington kept his look from the second movie, that might sway me a little. I am very shallow and I love a man with dirty blonde hair.

Emily: I would also choose Will, but I do, as a 27-year-old woman versus a 10-year-old girl, understand the appeal of Norrington being much more established, and a more stable life is appealing to me, personally, as a tired adult.

Petrana: Will as a blacksmith has a stable income, but Will as captain of the Flying Dutchman doesnt.

Karen: He doesnt have a stable income, and the only thing thats stable is he can only come see you once every 10 years or whatever. What do you guys think of the way Will and Elizabeths story ends?

Petrana: I was looking into this because I was curious. In the directors commentary, they say that, because Elizabeth was faithful to him, the curse was broken, which I clung to as a little girl. Of course, they retcon that in the fifth movie, but I loved that tragic trope. There is the big question of why she doesnt just go with him. Her dad is dead, so why not?

Karen: Yeah, there is nothing preventing her from going with him. But I guess if you want to live in a nice house you wouldnt go because the Flying Dutchman is not very nice. Now, I want to dig into Emilys comment about Captain Barbossa. Personally, I wouldnt not choose Barbossa.

Emily: I love Barbossa, especially as hes juxtaposed with Jack Sparrow, because where Jack is morally ambiguous and kind of loosey-goosey and his whole thing is this stumbling rockstar thing, Barbossa is not loosey-goosey. He is controlled, he is tight, he knows exactly what his code is, which is none. I love that he absolutely does not care about anything besides his very specific goals. When he bites into the apple and the juice runs down his face? Its hot. Im sorry. Also he has a monkey, and thats cool.

Karen: Did you find him attractive during the first movie or is this something that has cropped up as youve grown up?

Emily: In the first movie, I was terrified of him. By the third movie, I was into him. I was 15, and I was like, Yeah, I like this guy. I was still all-in for Will, but I had some tinglings of, What about him, though?

Karen: Petrana, Im curious if there are any other characters that you looked at and were like, Hm, I do like them.

Petrana: Im not even sure if its romantic but I think Tia Dalma deserves so much more. I want to know more about her and Calypso. Her whole thing is kind of handwaved. Also Naomie Harris is just a beautiful woman.

Karen: I like when she turns big and then turns into a bunch of crabs. I do like that thats her ending: I am a sea goddess, goodbye. My huge crush was Davy Jones. I was so obsessed with him when these movies came out, and for a long time afterwards. I dont know if my crush on Bill Nighy came first or if liked Davy Jones first, but hes just so mysterious and cool. When I was 13, I was so into him that my friends made me a poster that was just a collage of pictures of Bill Nighy on a bunch of printer paper. They also got me a little piece of official movie merch which was a pen with a Davy Jones head-topper on it, which I treasured. I think its still in my childhood bedroom. That one moment where he turns into a man in the moonlight was hot. Not that Davy Jones with a squid face wasnt hot ... I dont look at Davy Jones with a squid face and think, I want to kiss him, but I dont look at him and think I dont not want to kiss him.

Emily: I mean, if we want to talk crushes that the room will not relate to: Jonathan Pryce, man.

Karen: Hes a devoted dad and has a nice house!

Emily: I like the wig, but also when he takes off the wig. Hes got that messy wig hair. Its good. Also, those Turner genes are strong because Id absolutely smooch Bootstrap Bill. Stellan Skarsgrd ... hes daddy, I dont know what to tell you.

Karen: Big, big same. Hes a hunk! More of a hunk than Will, in my opinion. Those barnacles aint nothing to me! I do have to bring up that when we were discussing this roundtable, Emily, you brought up the pirate Ragetti.

Emily: Yes! Specifically because of the scene where theyre doing the ritual to return Tia Dalma to her true form as Calypso, and the ritual says they have to speak to her like theyre talking to a lover. I love Barbossa, but he does this big, performative voice, and then Ragetti just walks up to her and whispers into her ear. She does this little shiver. I would, too. Also, Mackenzie Crook is a cutie.

Karen: I do love Pintel and Ragetti a lot. They are extremely cute together. OK, so what if Pirates of the Caribbean was a dating sim? If you were playing it right now, who would romance?

Emily: I think Governor Swann, just to see if the game would let me.

Petrana: I will say that I would not pick Will because he and Elizabeth were a first OTP for me, and I wouldnt want to mess with it. I want go with Norrington because I think that would be a challenging route. Whenever Im playing a game with romance options I have to choose the one that would be an uphill battle. (Disclaimer: this is not how I approach real-life romantic relationships.)

Karen: You have to fix him. It reminds me of Cullens route in Dragon Age: Inquisition, where you have to get him over his drug addiction.

Petrana: I picked that route.

Karen: I know you did. Obviously, I would romance Davy Jones. He was always my number one in Pirates of Caribbean. I was never into Will, Jack, or Norrington. I am fully aware he was not in the first movie, but I dont care. I love him. I love his little claw. Hes like a big octopus! Also, I feel like a new relationship would be good for him.

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The Pirates of the Caribbean cast: who was the best love interest? - Polygon

Department of Genetic Medicine | Johns Hopkins Medicine

The McKusick-Nathans Institute of Genetic Medicine | Department of Genetic Medicineseeks to further the understanding of human heredity and genetic medicine and use that knowledge to treat and prevent disease.

The Department of Genetic Medicineis working to consolidate all relevant teaching, patient care and research in human and medical genetics at Johns Hopkins to provide national and international leadership in genetic medicine. The Department of Genetic Medicineserves as a focal point for interactions between diverse investigators to promote the application of genetic discoveries to human disease and genetics education to the public. It builds upon past strengths and further develops expertise in the areas of genomics, developmental genetics and complex disease genetics. The Department of Genetic Medicineworks to catalyze the spread of human genetic perspectives to other related disciplines by collaboration with other departments within Johns Hopkins.

There are more than 300 dedicated employees in the Department of Genetic Medicine, fulfilling the Johns Hopkins tripartite mission of research, teaching and patient care. They include 45 full-time faculty, 15 residents, more than 70 graduate students and 200 staff.

All too often, when we see injustices, both great and small, we think, that's terrible, but we do nothing. We say nothing. We let other people fight their own battles. We remain silent because silence is easier. Qui tacet consentire videtur is Latin for 'Silence gives consent.' When we say nothing, when we do nothing, we are consenting to these trespasses against us.Roxane Gay

The indifferent and arrogant murder of George Floyd is but one of many searing examples of racism, oppression and sheer wickedness imposed on members of the African-American community over the last 400 years. Repeatedly, over these many years, periods of apparent progress have been undercut by horrific acts of racially-based evil that expose an underlying hard core of racial bias and systematic racism. The sadness, anger and frustration we all feel are compounded by the failure of our society to respond to these events with real and sustained justice. We cannot, however, let these events undermine our quest for meaningful and sustained progress towards correcting the systemic problems and beliefs leading to these events. To quote Martin Luther King Jr., Change does not roll in on the wheels of inevitability, but comes through continuous struggle.

How can we break out of this cycle of modest progress punctuated by horrific failures? The answers to this question are neither simple nor obvious. Success will require a sustained and multi-faceted effort from all of us. Some reactions seem obvious and personally attainable; we must treat all members of our society equally and fairly. In these difficult times, we much reach out to those directly affected with understanding, respect, and support. All of us must commit to and participate in these positive interactions. Beyond these responses of the moment, we must search for ways that we can change the social, economic and personal environment to minimize the likelihood of recurrence and maximize progress towards real equality for all. As geneticists, we treasure diversity and understand many of the biological factors underlying it. Perhaps, one special responsibility for us is to help others in society understand and value diversity and individuality.

As members of the Human Genetics program and Department of Genetic Medicine community, we recognize there are some among us who are more vulnerable to the biases illuminated by the death of George Floyd and many, many others; whose fear of an encounter with the police is amplified by personal and community experience; and whose experience of pain and suffering far exceeds what most of us can fully understand. To those most vulnerable in our Department of Genetic Medicinefamily, we stand with you and raise our voices to support you. We are ready to listen and act in pursuit of a learning environment of which you can be proud and a world into which you will move and feel free to change.

Finally, as we search for appropriate responses, we are grateful to have your voices, your guidance to help illuminate a path forward. We recognize and are encouraged by the outpouring of activism, passion, rage and love from our students, our department, our community and even our own families. We also recognize that this journey, which began centuries ago, will be long, sometimes uncomfortable and inelegant and studded with setbacks. We are, however, committed to do everything in our power to speed its progress.

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Department of Genetic Medicine | Johns Hopkins Medicine

Genetic Medicine | Internal Medicine | Michigan Medicine …

As use of genomic technologies continue to increase in research and clinical settings, the Division of Genetic Medicine serves a key role in bringing together basic, clinical, and translational expertise in genomic medicine, with multidisciplinary faculty comprised of MDs, PhD scientists, and genetic counselors. Demand for expertise in genetics continues to increase, and the Division of Genetic Medicine is committed to advancing scientific discovery and clinical care of patients.

In addition to our Medical Genetics Clinic, genetics services are available through several other Michigan Medicine clinics and programs, including the Breast and Ovarian Cancer Risk Evaluation Program, Cancer GeneticsClinic,Inherited Cardiomyopathies and Arrhythmias Program,Neurogenetics Clinic, Pediatric Genetics Clinic, and Prenatal Evaluation Clinic.

Our faculty are focused on various research areas including cancer genetics, inherited hematologic disorders, neural stem cells,the mechanisms and regulation of DNA repair processes in mammalian cells, predictive genetic testing,understanding the mechanisms controlled by Hox genes, birth defects, bleeding and thrombotic disorders, and human limb malformations.

Division of Genetic Medicinefaculty are actively engaged in the education, teaching, and mentorship of clinicians, and clinical and basic scientists, including undergraduate and graduate students, medical students, residents, and fellows from various subspecialties.

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Genetic Medicine | Internal Medicine | Michigan Medicine ...

Genetic Medicine | Department of Medicine

Advances in molecular biology and human genetics, coupled with the completion of the Human Genome Project and the increasing power of quantitative genetics to identify disease susceptibility genes, are contributing to a revolution in the practice of medicine. In the 21st century, practicing physicians will focus more on defining genetically determined disease susceptibility in individual patients. This strategy will be used to prevent, modify, and treat a wide array of common disorders that have unique heritable risk factors such as hypertension, obesity, diabetes, arthrosclerosis, and cancer.

The Division of Genetic Medicine provides an academic environment enabling researchers to explore new relationships between disease susceptibility and human genetics. The Division of Genetic Medicine was established to host both research and clinical research programs focused on the genetic basis of health and disease. Equipped with state-of-the-art research tools and facilities, our faculty members are advancing knowledge of the common genetic determinants of cancer, congenital neuropathies, and heart disease. The Division faculty work jointly with the Vanderbilt-Ingram Cancer Center to support the Hereditary Cancer Clinic for treating patients and families who have an inherited predisposition to various malignancies.

Genetic differences in humans at the molecular level not only contribute to the disease process but also significantly impact an individuals ability to respond optimally to drug therapy. Vanderbilt is a pioneer in precisely identifying genetic differences between patients and making rational treatment decisions at the bedside.

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Genetic Medicine | Department of Medicine

Genomics and Medicine – Genome.gov

It has often been estimated that it takes, on average, 17years to translate a novel research finding into routine clinical practice. This time lag is due to a combination of factors, including the need to validate research findings, the fact that clinical trials are complex and take time to conduct and then analyze, and because disseminating information and educating healthcare workers about a new advance is not an overnight process.

Once sufficient evidence has been generated to demonstrate a benefit to patients, or "clinical utility," professional societies and clinical standards groups will use that evidence to determine whether to incorporate the new test into clinical practice guidelines. This determination will also factor in any potential ethical and legal issues, as well economic factors such as cost-benefit ratios.

The NHGRIGenomic Medicine Working Group(GMWG) has been gathering expert stakeholders in a series of genomic medicine meetingsto discuss issues surrounding the adoption of genomic medicine. Particularly, the GMWG draws expertise from researchers at the cutting edge of this new medical toolset, with the aim of better informing future translational research at NHGRI. Additionally the working group provides guidance to theNational Advisory Council on Human Genome Research (NACHGR)and NHGRI in other areas of genomic medicine implementation, such as outlining infrastructural needs for adoption of genomic medicine, identifying related efforts for future collaborations, and reviewing progress overall in genomic medicine implementation.

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Genomics and Medicine - Genome.gov

New Approach to Treating Osteoarthritis Advances | NYU Langone News – NYU Langone Health

Injections of a natural energy molecule prompted regrowth of almost half of the cartilage lost with aging in knees, a new study in rodents shows.

The study results revolve around the long-established idea that machines within animal and human cells turn the sugars, fats, and proteins we eat into energy used by the bodys millions of cells. The molecule most used to store that energy is called adenosine triphosphate, or ATP. Along with this central role in metabolism, adenosine also helps signal other cells and serves as a building block of genetic material, and so is central to the growth of human tissue.

Previous research had shown that maintaining supplies of adenosine, known to nourish the chondrocyte cells that make cartilage, also prevented osteoarthritis in similar animal models of the disease.

In the new NYU Grossman School of Medicineled study, researchers injected adenosine into the joints of rodents whose limbs had been damaged by inflammation resulting from either traumatic injury, such as a torn ligament, or from massive weight gain placing pressure on joints. The biological damage in these cases is similar, researchers say, to that sustained in human osteoarthritis.

Published online in the journal Scientific Reports on August 10, the study rodents received 8 weekly injections of adenosine, which prompted regrowth rates of cartilage tissue between 50 percent and 35 percent as measured by standard laboratory scores.

Our latest study shows that replenishing adenosine stores by injection works well as a treatment for osteoarthritis in animal models of the disease, and with no apparent side effects, says lead study author Carmen Corciulo, PhD, a postdoctoral fellow at NYU Langone.

Dr. Corciulo says it is too soon to use this experimental model as a therapy in people. Clinical trials must await a test drug that can be safely stored for days if not weeks, and experiments in larger mammals.

Study senior investigator Bruce N. Cronstein, MD, the Dr. Paul R. Esserman Professor of Medicine at NYU Langone Health, says the teams research is important because the few existing drug therapies for osteoarthritis such as acetaminophen and COX-2 inhibitor drugs, including naproxen and ibuprofen, only numb joint pain, or like hyaluronic acid just lubricate its tissues. None stall disease progression or reverse the damage. Painkillers, such as opioids, are often prescribed, but are also highly addictive, he cautions.

People with osteoarthritis desperately need more treatment options with fewer side effects, and our research advances that effort, says Dr. Cronstein, who also serves as the director of NYU Langones Clinical and Translational Science Institute. He notes that other experimental medications are being developed elsewhere, including parathyroid hormone to stimulate bone growth, WNT inhibitor drugs to block the bone and cartilage degradation, and growth factor chemicals to promote cartilage growth.

Dr. Cronstein, Dr. Corciulo, and NYU Grossman School of Medicine have a patent application pending for the use of adenosine and other agents that help with its binding to chondrocytes, called A2A receptor agonists, for the treatment of osteoarthritis.

Among the studys other key findings was that a cell-signaling pathway, known as transforming growth factor beta (TGF-beta) and involved in many forms of tissue growth, death, and differentiation, was highly active in cartilage tissue damaged by osteoarthritis, as well as in cartilage tissue undergoing repair after being treated with adenosine. Additional testing in lab-grown chondrocytes from people with osteoarthritis showed different chemical profiles of TGF-beta signaling during breakdown than during growth, providing the first evidence that the pathway switched function in the presence of adenosine (from assisting in cartilage breakdown to encouraging its repair.)

Developing treatments to halt or slow the disease is important, Dr. Cronstein says, because well over 100 million people worldwide are estimated to have osteoarthritis, which is tied to aging, especially in women. This figure, he says, is only expected to grow as more people live longer and obesity rates climb.

Right now, the only way to stop osteoarthritis is to have affected joints surgically replaced, which not only comes with pain and risk of infection, but is also quite costly, says Dr. Cronstein. If new therapies can delay or prevent disease onset and progression, then fewer joint replacements will save people from a lot of pain and expense.

The study was funded by National Institutes of Health grants R01 AR056672 and R01 AR068593, NYU-HHC Clinical and Translational Science Institute grant UL1 TR000038, and the Arthritis Foundation.

Dr. Corciulo and Dr. Cronstein have a patent for the methods and compositions for treating osteoarthritis and promoting cartilage formation (U.S. Patent 10,441,541), which has been assigned to NYU Grossman School of Medicine. They are cofounders of Regenosine Inc., a company that is developing new treatments for osteoarthritis, and in which they hold a financial interest. Dr. Cronstein has consulted for Eli Lilly, Horizon Pharmaceuticals, Bristol Myers Squibb, and Astrazeneca. He also has grants from Arcus Biopharma. All relationships are being managed in accordance with the policies and practices of NYU Langone.

Besides Dr. Cronstein and Dr. Corciulo, other NYU Langone investigators involved in this study are Cristina Castro, MD; Thomas Coughlin, PhD; Samson Jacob, MS; David Fenyo, PhD; Daniel B. Rifkin, PhD; and Oran Kennedy, PhD.

David MarchPhone: 212-404-3528david.march@nyulangone.org

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New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health

Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates – Business Wire

BEDFORD, Mass.--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of genetic diseases by precisely upregulating protein expression, today reported financial results for the second quarter of 2020 and provided business updates.

Today we are announcing that the first patient has been dosed with STK-001, which we believe has the potential to be the first-disease modifying medicine for Dravet syndrome, a severe and progressive genetic epilepsy that is characterized by developmental delays and cognitive impairment, in addition to seizure activity, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. The start of MONARCH also marks Stokes official transition to a clinical-stage biotech company. We enter this new stage in a strong financial position to execute on our plans for STK-001 in Dravet syndrome and continue to advance the potential of our TANGO platform for additional genetic diseases.

Second Quarter 2020 Business Highlights and Recent Developments

Upcoming Anticipated Milestones

Second Quarter and Year-to-Date Results

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the FDA as a potential new treatment for Dravet syndrome.

About Phase 1/2a Clinical Study (MONARCH)

The MONARCH study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a pathogenic genetic mutation in the SCN1A gene. The primary objectives for the study will be to assess the safety and tolerability of STK-001, as well as to characterize human pharmacokinetics. A secondary objective will be to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 12-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life as secondary endpoints. Stoke plans to enroll approximately 40 patients across 20 sites in the United States.

About Dravet Syndrome

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include severe intellectual disabilities, severe developmental disabilities, motor impairment, speech impairment, autism, behavioral difficulties and sleep abnormalities. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK) is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: future operating results, financial position and liquidity, the direct and indirect impact of COVID-19 on our business, financial condition and operations, including on our expenses, supply chain, strategic partners, research and development costs, clinical trials and employees; our expectation about timing and execution of anticipated milestones, responses to regulatory authorities, expected nomination of a second product candidate and timing thereof, and our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize STK-001 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; environmental risks; risks relating to the use of social media for our business; and the other risks and uncertainties that are described in the Risk Factors section of our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking statements.

Financial Tables Follow

2020

2019

$

201,930

$

222,471

3,528

3,281

77

9

281

$

205,544

$

226,033

205

205

1,642

2,823

2,512

$

210,214

$

228,750

$

904

$

751

4,901

3,350

$

5,805

$

4,101

1,009

221

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Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire

Here’s Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today – Motley Fool

What happened

Shares of Editas Medicine (NASDAQ:EDIT) and Beam Therapeutics (NASDAQ:BEAM) rose as much as 23% and 29%, respectively, today after the pair were rumored to be considering a merger. Although investors shouldn't invest based on speculation, a merger would make sense on multiple fronts.

The duo already have an agreement in place to collaborate on genetic medicines, but the struggling pipeline of Editas Medicine could receive a significant boost from Beam Therapeutics. It would also allow Editas shareholders to avoid many of the technical pitfalls of first-generation CRISPR gene-editing tools, which have yet to be adequately reflected in stock prices. Of course, the flip side is that the merger doesn't make as much sense for Beam Therapeutics.

As of 12:50 p.m. EDT, both small-cap stocks had settled to gains of about 14%.

Image source: Getty Images.

There are multiple reasons a merger makes sense. Consider that:

There's not much to the report that Editas Medicine and Beam Therapeutics are considering a merger. Only one digital publication mentions "chatter" without providing any follow-up details. The rumors are at least plausible given the ties to the Broad Institute and overlap of the scientific founders, but investors simply don't have much to go on. That said, a merger would make more sense for Editas Medicine than Beam Therapeutics, as the latter has a much stronger technical foundation to lean on for the long haul.

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Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool

Grant will fund study into COVID outcome disparities in NYC – Cornell Chronicle

Weill Cornell Medicines Clinical and Translational Science Center (CTSC) has been awarded a grant from the National Institutes of Health to investigate the role of social and biological factors in determining COVID-19 severity and outcomes in New York City patients.

The two-year, $1.5 million grant will fund projects led by Dr. Julianne Imperato-McGinley, director of the CTSC and The Abby Rockefeller Mauz Distinguished Professor of Endocrinology in Medicine at Weill Cornell Medicine.

The projects co-leaders are Dr. Olivier Elemento, director of the Englander Institute for Precision Medicine and professor of computational genomics in pathology and laboratory medicine at Weill Cornell; and Dr. Said Ibrahim, professor of health care policy and research and senior associate dean for diversity and inclusion at Weill Cornell.

Black and Latino populations have suffered a significantly higher proportion of infection and death from COVID-19 in New York City and across the country. Social determinants of health including lack of access to adequate medical care, crowded housing and exposure from ones occupation can influence the likelihood of acquiring COVID-19.

Co-morbidities such as obesity, diabetes and lung and heart disease that put people at risk for severe illness are also more common in Black and Latino populations.

To assess how socioeconomic factors have contributed to the racial and ethnic disparities, the investigators will compare rates of hospitalization, intensive care unit admissions and deaths from COVID-19 in affluent versus lower income communities within New York City. They will also use data from patients across the NewYork-Presbyterian Hospital system to study patterns in demographics, laboratory results and biospecimens to determine if theres a link between genetic variability, race and ethnicity and severity of COVID-19.

The project builds on Weill Cornell Medicines vision of a clinical research program that combines clinical care, investigation into social determinants of health and basic science research. Leveraging CTSC infrastructure, this approach brings together sources like census and other government data, electronic health records and the institutions newly created biobank of COVID-19 patient specimens.

The team plans to use its findings to build a model to predict who is most susceptible to the disease, which can help shape prevention and treatment strategies and bring precision medicine to COVID-19 patients. The team also aims to expand its work to regional and national analyses, tapping into a database of clinical data from COVID-19 patients that is being assembled by the Clinical and Translational Science Award program national network.

Bridget Kuehn is a freelance writer for Weill Cornell Medicine.

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Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle

A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate – Science Advances

Dynamically adjustable gene- and cell-based therapies are recognized as next-generation medicine. However, the translation of precision therapies into clinics is limited by lack of specific switches controlled by inducers that are safe and ready for clinical use. Ferulic acid (FA) is a phytochemical with a wide range of therapeutic effects, and its salt sodium ferulate (SF) is used as an antithrombotic drug in clinics. Here, we describe an FA/SF-adjustable transcriptional switch controlled by the clinically licensed drug SF. We demonstrated that SF-responsive switches can be engineered to control CRISPR-Cas9 systems for on-command genome/epigenome engineering. In addition, we integrated FA-controlled switches into programmable biocomputers to process logic operations. We further demonstrated the dose-dependent SF-inducible transgene expression in mice by oral administration of SF tablets. Engineered switches responsive to small-molecule clinically licensed drugs to achieve adjustable transgene expression profiles provide new opportunities for dynamic interventions in gene- and cell-based precision medicine.

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A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances

Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical…

PHILADELPHIA, Aug. 10, 2020 (GLOBE NEWSWIRE) -- Spark Therapeutics, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced the appointment of Gallia Levy, M.D., Ph.D., as chief medical officer. Dr. Levy will be responsible for strategic and operational leadership across all functions in the product development lifecycle, including setting the global development strategy for current and future pipeline programs.

We are thrilled to welcome Dr. Gallia Levy to our growing gene therapy company striving to create a world where no life is limited by genetic disease, said Jeffrey D. Marrazzo, chief executive officer, Spark Therapeutics. Dr. Levys passion for hematology and gene therapy research is immediately evident and exactly the perspective needed to achieve our goal of unlocking the full potential of gene therapy. Especially during this pivotal time in hemophilia research, Dr. Levys deep understanding of rare blood disorders and the community will help accelerate our ability to deliver potentially transformative gene therapies for hemophilia, while progressing potential gene therapies for other genetic disease across our pipeline.

Dr. Levy joins Spark Therapeutics from Genentech, also a member of the Roche Group, where she served as the Vice President and Global Head of the Rare Blood Disorders franchise in Product Development. In this role, she was responsible for the clinical development of HEMLIBRA for hemophilia A as well as treatments for other rare blood disorders such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). She played a key role in the evolution of gene therapy as a new modality within the Roche Group.

Ive spent my career working to find new, innovative treatment approaches for patients affected by rare, life-altering disorders, and it is with great pride that I join the Spark team to help advance novel gene therapy programs and create next-generation solutions for patients, said Dr. Levy. Spark Therapeutics shares the same affinity for breaking barriers and putting the patient first, and I look forward to what we will achieve together.

Dr. Levy first joined Genentech in 2009, where she worked in both early and late-stage clinical development. She later moved to Portola Pharmaceuticals, where she led the clinical development program for hematology and oncology indications and returned to Genentech in 2014 to lead the hemophilia program.

Dr. Levy is board-certified in hematology and holds an M.D. and Ph.D. in Molecular and Cellular Biology from the University of Michigan. She completed her residency in internal medicine at Stanford University and a fellowship in hematology and oncology at the University of California, San Francisco. She also holds an M.S. in of Molecular and Cellular Biology from the University of Paris, VI and a B.A. from the University of California, Berkeley.

About Spark Therapeutics AtSpark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challengethe inevitability of genetic diseases,includingblindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases.We currently have four programs in clinical trials.At Spark, a member of the Roche Group, we see the path to a world where no life is limited by genetic disease. For more information, visit http://www.sparktx.com, and follow us on Twitter and LinkedIn.

Media Contact:Kevin Giordanokevin.giordano@sparktx.com(215) 294-9942

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Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical...

Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP – JD Supra

Chemotherapeutic drug resistance is one reason cancer remains an unsolved clinical problem despite the efforts ever since President Nixon declared his "War on Cancer" in 1971. Cancer cells, due in part to the genetic destabilization characteristic of the disease, are capable of expressing genes (normal or aberrant) that permit the cell to avoid the cytotoxic effect of such drugs with the patient providing the situs of selection for and growth of resistant cells. The phenomenon is certain tumor types can have more deleterious consequences than in others, and this is particularly true for glioblastomas (and their non-malignant counterparts, gliomas), cancer of the cells that protect neurons in brain. That organ, confined to the skull, cannot accommodate tumor growth without damaging the brain with which it is confined.

The chemotherapeutic drug of choice for treating glioblastomas is temezolomide (TMZ), an oral alkylating agent that had its chemotherapeutic effect by introducing alkyl groups onto nucleotide bases (preferably at the N-7 and O-6 positions of guanine and N-3 position of adenine) in tumor cell DNA preferentially (due to the greater amount of DNA synthesis occurring in these cells) and disrupting the process leading to cell death (the O-6 methylation having the greatest capacity to induce apoptosis or programmed cell death).O-6-methylguanosnine DNA methyltransferase (MGMT) is the cellular enzyme responsible for repairing alkylated bases in DNA and reduced expression of this gene (e.g., by hypermethylation of the MGMT promoter) is a biomarker for TMZ sensitivity in gliomas and glioblastomas. Recently, a multinational team of researchers* reported genetic rearrangements associated with TMZ resistance, in a paper entitled "MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas" published in Nature Communications. This paper shows a subset of gliomas with rearrangements in the MGMT gene that produce overexpression of the gene and resistance as a result. These authors screened 252 TMZ-treated recurrent gliomas by RNA sequencing and found eight different MGMT genetic fusions (designated BTRC-MGMT,CAPZB-MGMT,GLRX3-MGMT,NFYC-MGMT,RPH3A-MGMT, andSAR1A-MGMTin high-grade gliomas, HGG, andCTBP2-MGMTandFAM175B-MGMT in low-grade gliomas, LGG, in the paper) in seven patients (6 females) with recurrent disease, created by chromosomal rearrangement (see Figure 1c from paper; shown below). These individuals' tumors showed "significantly higher" expression of the rearranged MGMT gene product.

Upon further study, the authors report that five of the eight rearranged genes were located on Chromosome 10 in the vicinity of the MGMT gene itself. The breakpoint in the MGMT was uniformly found at the boundary of exon 2 of the MGMT gene, at a point 12 basepairs upstream of the ATG translation "start" codon. In three of the rearrangements, the breakpoint in the partner gene in the genetic fusion was found in the 5' untranslated region (UTR). All fusions were found to be in-frame (i.e., the reading frame of the MGMT transcript was not disrupted) and the functional regions of the MGMT protein (the methyltransferase domain and DNA-binding domain) were intact. A more fine-structure mapping experiment in the genetic rearrangement resulting in FAM175B-MGMTfound that the fusion was the consequence of a deletion of 4.8 Mb.

The effect of these rearrangements on MGMT expression was elucidated using CRIPSR-Cas9 to produce the BTRC-MGMT, NFYC-MGMT, SAR1A-MGMT, and CTBP2-MGMT rearrangements in cells of two glioblastoma cell lines, U251 and U87. When these cells and their untreated counterparts were challenged by growth in vitro with TMZ, only cells bearing the rearrangements (as confirmed by PCR analysis) were shown to be TMZ resistant. Unlike genetic rearrangements in other cancers that produce fusion proteins (such as the abl-bcr gene produced in chronic myelogenous leukemia bearing the diagnostic Philadelphia chromosome), because most of the rearrangements found involving the MGMT gene were located upstream of the initiation codon of the MGMT gene these authors reasoned that these rearrangements produce increased expression of MGMT leading to TMZ resistance because the cells were better able to repair the methylation injury and replicate functionally. This hypothesis was supported by real-time quantitative PCR analysis of MGMT transcripts in cells bearing the rearrangements, that showed a "striking" increase in expression of MGMT-encoding transcripts (an observation also found in tumors from patients whose gliomas or glioblastomas showed these rearrangements), and Western blot analysis confirmed higher expression levels of the MGMT protein. In two of the rearrangements (BTRC-MGMT and NFYC-MGMT), higher molecular weight fusion proteins were detected as predicted from the genetic data. These results were also replicated in patient tumor-derived stem cells for the BTRC-MGMTandSAR1A-MGMT rearrangements.

These results, and the researchers' conclusion that these rearrangements caused TMZ resistance by overexpression of MGMT, were confirmed by re-establishing TMZ sensitivity in these cells in the presence of O6-benzylguanine (O6-BG), an MGMT inhibitor. These results were further confirmed by detection of double-strand breaks in DNA in these cells in the presence of TMZ and O6-BG.

The relevance of these results to TMZ resistance in vivo was demonstrated using nude mouse xenograft models bearing tumors produced using BTRC-MGMT U251 cells and U251 cells without the rearrangement as control; these cells also contained a recombinant luciferase gene. Mice containing the rearrangement showed no significant prolongation of lifespan in the presence or absence of TMZ, indicating tumor cell resistance, whereas TMZ treatment of nave U251 cells showed improved survival.

While hypomethylation of the native MGMT promoter is the most frequently change associated with TMZ resistance, the results presented in this paper illustrate an alternative mechanism for glioblastomas and gliomas to acquire resistance to TMZ, the only current chemotherapeutic drugs for these maladies. Because these rearrangements were found in patients with recurrent tumors, these authors hypothesize that the rearrangements were selected or by TMZ treatment. A similar rearrangement has also been found in another cancer, medulloblastoma, after TMZ relapse. These authors also suggest that detection of these rearrangements can be used clinically to determine appropriate treatment modalities, particularly for recurrent disease.

* Seve Ballesteros Foundation Brain Tumor Group, Molecular Oncology Programme, Spanish National Cancer Research Center; Division of Life Science, Department of Chemical and Biological Engineering, Center of Systems Biology and Human Health and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology; Beijing Neurosurgical Institute, Capital Medical University; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Systems Biology, Columbia University; The Jackson Laboratory for Genomic Medicine; and Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Center, CNIO, 28029, Madrid, Spain

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Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra