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The Cult Sports Movie That Tackled the Underbelly of Fandom – The Ringer
Posted: January 29, 2021 at 11:46 am
This week on The Ringer, we celebrate those movies that from humble or overlooked beginnings rose to prominence through the support of their obsessive fan bases. The movies that were too heady for mainstream audiences; the comedies that were before their time; the small indies that changed the direction of Hollywood. Welcome to Cult Movie Week.
As a Long Island kid in the late 1970s and 80s, Robert Siegel would lay under his covers at night and listen to sports-talk radio. He still remembers the callers thick accents. Always guys from Queens, always guys from Brooklyn, the filmmaker says. I was living my sheltered, suburban Jewish experience. Those people in other parts of New York were so exotic.
They were the kinds of memorably downtrodden minor figures that populated Siegels favorite movies: Midnight Cowboy, Taxi Driver, Saturday Night Fever. But hed never seen a film about the type of aging schlub whod phone WFAN and patiently stay on hold for hours just for a chance to air his grievances with pro athletes who werent even listening. So in the early 2000s, while serving as the editor in chief of satirical publication The Onion, he decided to write one himself. Those voices I heard were ingrained in my head, burned into my brain from my teenage years, says Siegel, who as a child shunned the mediocre Jets and Giants for the Steelers. It very easily translated into a 70s-style, gritty character study.
Initially titled Paul Aufiero, the script centered on a 35-year-old Staten Island man who lives for the New York Giants and with his mother. He sleeps on a bed covered in NFL team sheets; a poster of his favorite player, Quantrell Bishop, hangs on the wall of his bedroom; he spends too much of his time both listening and calling in to a radio show hosted by the Sports Dogg. He bleeds blue, but doesnt have anything else in his life. His allegianceand entire existenceis tested, however, when Bishop nearly beats him to death in a strip club.
There are plenty of movies about the underbelly of sports, but only a few about the underbelly of sports fandom. Siegels screenplay explored what can happen when obsession overtakes identity. Uncoincidentally, Pauls very first line of dialogue, part of a rant to the Sports Dogg, is: I cant tell you how sick I am
Ive never read anything like what Rob writes, says Capone, Fantastic Four, and Chronicle director Josh Trank, who collaborated with Siegel on the project. Its not super colorful. If anything, its ridiculously economical, to a point where its almost as if the author of the words that youre reading doesnt want to get in between you and the basic experience of just being there with these characters.
By the time Siegels script landed in the hands of Patton Oswalt, it had been floating around Hollywood for the better part of a decade. The story reminded the comedian of intimate 70s classics like Five Easy Pieces and Wanda. Instead of going into some convoluted plot or big concept, were going to hang out with this character, warts and all, he says. You go deep into one person, and that opens up the world in a weird way.
But like many other original ideas before it, what eventually became Big Fan took a circuitous route to the big screen. And when the dramatic comedy did get made, it was a flop. But since its release in 2009, Siegels self-financed directorial debut has gained a cult following for the way it predicted the dangers of toxic fanboyism, just as social media had begun to supercharge its ugliness.
Prior to Big Fan, pragmatism fueled Siegels screenwriting career. Hed written what he knew: comedies. Then, during his faux news organizations annual three-week publishing break in the summer of 2002, he stopped worrying about churning out a script that could sell and instead worked on one that actually interested him.
Like countless New Yorkers, Siegel loved sports and Martin Scorsese. The Long Islander knew that he wanted his homage to his idol to revolve around a laughably small-minded fan who lived in a laughably small world. Hes a far more gentle but just as obsessive version of Travis Bickle or Rupert Pupkin.
Before calling into the Sports Dogg, Paul has to write out his diatribes. His mother laments that the only woman hes dating is his hand and scolds him for the doo-doo stains that she sees while washing his underpants. He snarfs the edible photo of 50 Cent on his nephews birthday cake and retchingly pours sugar into his regular Coca-Cola. (My dad used to do that, Siegel says.) While following Bishop from a gas station to Stapleton, Staten Island, at 10:45 p.m., hes too naive to realize that the Giants linebacker is picking up drugs.
Before starting to write, Siegel had to visit an acquaintance at a hospital. Upon entering and later exiting the parking garage, he wondered what the cashiers life was like. At that moment, Siegel knew that Paul should toil as a booth attendant. Youre in the crosshairs of people who are just having the worst day of their lives, Siegel says. Sometimes you have an idea gestating and then theres some image that crystalizes it for you.
Siegel wrote Paul Aufiero in 10 days: Its never happened before or since where something just poured out of me. Without seeking any notes from development executives, he gave the script to his agent. Soon, there was an intrigued party: Darren Aronofsky. Over several meetings at coffee shops, the director of Requiem for a Dream and Siegel talked about the potential films direction. But then they had a problem. The NFL issue, Siegel says.
Unsurprisingly, the league doesnt take kindly to being associated with films and TV shows as raw as Big Fan. The ESPN series Playmakers and Oliver Stones Any Given Sunday used fictional franchises for a reason. The NFL is notoriously litigious, Siegel says. I mean, they have a rich history of lawsuits. Even if theres nothing really objectionable, they just protect the shield. They will sue you.
To make matters worse, all the major movie studios other than Sony were affiliated with networks that aired professional football games. Fox, NBC, and CBS each pay around $1 billion annually to broadcast the Sunday NFL slate; when the current rights deal is renegotiated next year, that figure may double. It makes sense that megacorporations wouldnt want to jeopardize their lucrative relationship with the league for a tiny indie flick with zero blockbuster potential.
Aronofsky, and Siegel for that matter, had little desire to make a movie about a disturbed fan of a fake team. Without the presence of Giants logos and paraphernalia, Pauls obsession just wouldnt feel real. And so the screenplay languished. Trank first came across it when he was in his late teens; a friend of Amy Heckerlings daughter, Trank had become an unofficial assistant to the Clueless director. I was getting deeper and deeper into reading scripts, Trank says. Amy said to me, You want to read a great script? Heres this.
At one point or another, Paul Rudd, Rainn Wilson, Jason Reitman, and Todd Field all expressed interest in Siegels script. But none ever fully committed. Aronofsky moved on, too, but was so impressed with Siegels work that he hired him to write another bleak sports movie. This one, The Wrestler, did get madeto great acclaim. Yet even after working on an Academy Awardnominated film, Siegel couldnt find any backers for his dream project. Finally, he took matters into his own hands.
I just wanted this movie to exist, Siegel says. I said, The only way Im going to do it is if I do it myself and if I self-finance it. So thats what I did.
Coming off of The Wrestler, Siegel was able to put up $250,000 of his own money. In hindsight, dropping a quarter of a million dollars on a passion project wasnt pragmatic. After all, his wife was pregnant. To my never-ending gratitude, he says, she was cool with it.
In search of guidance as to whether the NFL would actually sue him, Siegel sent his screenplay to Michael Donaldson, an entertainment attorney whos worked extensively with independent filmmakers on rights issues. To Siegels shock, the veteran lawyer told him, You can do this.
I said, Well, what can I do? Siegel remembers. He says, You can do anything. You can show the logos. You can have the jerseys. You can talk about the teams. You can make up fictional players. The only thing Donaldson advised against was using actual game footage. Beyond that, Siegel recalls him saying, everything is fair use.
When it was time to find his Paul Aufiero, Siegel immediately targeted Patton Oswalt. Back in the aughts, Oswalt was best known for his stand-up and for his role on the sitcom The King of Queens. And while the comedian had voiced Remy in Pixars Ratatouille, hed never carried a live-action movie. He also wasnt a sports fanbut Siegel thought he could still understand the concepts of arrested development and obsession. He just fit exactly what I wanted, Siegel says. Hes not a sports fan, but nerdy obsession is nerdy obsession, whether its the New York Giants or the MCU.
Oswalt was a cinephile, a comic book nerd, and a voracious reader. Hed also written extensively about his own geekdom. I understand wanting something bigger than yourself, Oswalt tells me. Everyone, I think, will find a different version of it, one way or the other. That same kind of nerdy passion for other thingsfilms, comics, booksI was just able to transfer to sports. Its the same spark, its just different fuel.
Even with barely any money, Siegel managed to assemble a small but talented cast of decorated character actors around Oswalt. Marcia Jean Kurtz plays Pauls exasperated single mother, Theresa; Kevin Corrigan is his best friend Sal; and Michael Rapaport appears mostly as the disembodied voice of the rival sports-radio caller Philadelphia Phil. (The main reason Siegel made the working-class Paul a Giants fan and not a Jets fan was because Gang Green didnt have a historical rival like the Eagles.)
It was a very human script, very deeply human, Kurtz says. [It] really cared for these lonely people.
I was a big fan of Patton for years, Corrigan said in an email. Id seen him perform. I had all his records. In the movie, Sal looks up to Paul. He loves listening to his friend. He loves Pauls act. I really felt that way about Patton.
Gino Cafarelli, who plays Pauls ambulance-chasing brother Jeff, remembers getting a phone call from Siegel about the part. He goes, I was scanning through YouTube and I punched in character actor and New York character actor, Cafarelli says. And he said every time he kept punching it in, my reel kept on coming up.
For the Sports Dogg, whom the audience never sees, Siegel needed a distinct voice. He found one in the gravel-throated, then-Sirius sports-radio host Scott Ferrall. He understood men like Pauland how to tee them up. Im like their shrink and Im like their lover, Ferrall says. Im like their dealer. Im like their best pal. And theyll tell me all their deepest thoughts.
Not that Paul even has any deep thoughts. His screeds rarely amount to much more than boilerplate talking points about Eli Manning. He has, Siegel says, a very low level of self-awareness.
Without meeting Oswalt, Ferrall recorded his part in his studio over two long sessions. I just started going crazy, says Ferrall, who was given talking points but ad-libbed most of his lines. And I remember just flipping out and screaming and yelling and arguing and doing like I would do a talk show.
The more Ferrall learned about Oswalts character, the more he felt familiar. What was strange about it, the broadcaster says, was that I think at least 20 percent of my callers are like him.
His movies micro budget may have necessitated a guerilla-style shoot, but Siegel vowed not to sacrifice realism or detail. Without permission to film in the Giants Stadium parking lots, he did it anyway, collecting B-roll and shots of Oswalt and Corrigan wearing team gear among throngs of tailgaters.
For a scene in which the two ticketless buddies watch the game on a box TV powered by Pauls moms beat-up car, the director got a permit to film at the adjacent Meadowlands Racetrack. Theyre like, You want to shoot something in our parking lot during a race? Go ahead. Knock yourself out, Siegel says. If you take your camera and you rotate it 180 degrees, Oh my God, look. Whats this? Giants Stadium!
Producer/location manager Nick Gallo, an Onion alum who worked at Auntie Annes Pretzels at the Staten Island Mall in the 90s, offered his familys homes as filming locations. Nicks grandmas parakeet was traumatized, Trank says. It was very sad afterward.
Unsurprisingly, the actors had few creature comforts. Not that it bothered them. I dont mind changing out of a car if its a great script, Cafarelli says. He means that literally: Cafarelli got into costume in a Nissan Sentra, while Oswalts dressing room was the back of a van. Catering was, they would go to Subway every day, Oswalt says. It was just the most basic, bare bones. Really cool, you know?
The DIY production fostered camaraderie. Between takes, Corrigan recalls, Oswalt would bring up his favorite Onion stories and headlines and Siegel would tell their backstories. (Our Dumb Century, everything about that book was just genius, Oswalt says.)
As both a director and a sports fan, Siegel paid close attention to detail. While talking about the Giants defense in one scene, Oswalt emphasized the second syllable of the word rather than the first. The mispronunciation seemed innocuous, but it was the kind of thing that the director wouldve flagged as inauthentic if he heard it in another movie. Im like, I dont think people care, Trank says. And hes like, Theyll care.
If theres one thing that Oswalts lack of sports knowledge prevented him from doing in Big Fan, it was improvising. For someone who once delivered an eight-minute Star Wars filibuster in an episode of Parks and Recreation, it was like being comedically handcuffed. Ultimately, though, that hindrance likely strengthened his performance. After all, Paul Aufiero is neither smart nor worldly. There were moments when I would riff stuff, and then I would stop and go, Hell, he doesnt have the inner resources to riff like that, Oswalt says. Me and Robert were very, very open about this guy not having clever things to say. Hes kind of a void. And Im glad we stuck to that.
By the end of a lesser film, Paul wouldve learned some lessons. Hed maybe figure out that blind devotion is dangerous. And possibly, hed realize that there should be more to a grown mans life than worrying about whether his team wins on Sunday afternoons. But Big Fan isnt a normal sports movie.
After his accidental provocation at a strip club causes Bishop to attack him, a traumatized Paul seems tortured. His lawyer brother wants him to sue. A detective wants him to testify against the linebacker. Adding insult to injury, Philadelphia Phil goes on the Sports Dogg and doxxes him as Bishops assault victim. But despite nearly dying at the hands of his favorite player, despite the fact that hes become a local pariah, he still doesnt want to mess up the Giants season.
He definitely feels the vice, Siegel says. He feels the screws are being put to him by his brother, by Philadelphia Phil. He feels like the teams fate rests in his hands. Hes definitely spending that middle stretch of the movie with just a sick feeling in his gut.
Yet instead of doing the logical thing, Paul calls a trick play. After Philadelphia Phil mockingly invites him to switch allegiances and watch the Eagles-Giants season finale with him and his buddies at a sports bar, Oswalts character heads south, stopping only to throw on a Donovan McNabb jersey and paint his face green and white. During Pauls drive, Siegel makes sure to include a shot of a pistol sticking out of Pauls pants.
For a few minutes, it truly feels like Paul from Staten Island might kill Philadelphia Phil. But his version of revenge is somehow even more warped than that. After cornering the Eagles fan in the bathroom, Paul empties a clip. At first it looks like Rapaports hands and Reggie White jersey are covered in blood. But after a moment, it becomes clear that the red splatter is mixed with blue. Paul has shot Phil with a paintball gun. To Paul, covering an Eagles fan with Giants colors is worse than killing him. But crucially, hes not quite a Taxi Driverstyle vigilante.
The way that Travis Bickle is portrayed is he is someone who is spurred to some kind of action because he has seen real violence and real pain, Oswalt says. Hes got that scar. He was in Vietnam. I just dont think that Paul has ever really experienced the world at all. So, when his so-called life force swells up, even the expression of the life force is just this weird, symbolic thing of just spraying his enemy with his teams colors. Hes so cut off from humanity, he doesnt even know how to do violence correctly.
The crushingly funny reveal ends with Paul telling Philadelphia Phil that the Eagles suck, running out of the bar, and getting tackled by the cops. Trank calls the climax of Big Fan one of his top-five favorite endings ever.
Pauls love for his team is tested, but in the end it never caves. You can struggle without ever actually being truly undecided, says Siegel. I mean the question the movie asks is, What do you do when this thing you love doesnt love you back? That could be a team. That could be a president. These are all forms of abusive relationships. Hes in an abusive relationship with the New York Giants. You reach a point when that thing you believe in punches you in the face. You have this moment where you have to decide, Do I take this as a turning point and turn my back on this thing? Or do I double down?
One way to answer those questions cinematically is via a romantic comedy like the Jimmy FallonDrew Barrymore movie Fever Pitch. But thats pure fantasy. Siegel was interested in real life.
It is one of those great movies where its realistic to a fault, Oswalt says. The character does not grow or change. He fights against change, and his victory at the end is that he doesnt change.
In January of 2009, Big Fan premiered to positive reviews at the Sundance Film Festival. But mid-financial crisis, a sports movie that featured no sports and no big stars didnt entice many buyers. Its like, Well, I cant fit it into this category, Trank says. So Im not going to risk it.
Late that winter, the film sold to a small distributor called First Independent Pictures. It opened on August 28, first in just two theaters in America, then eventually in 15. This was not going to be in 1,000 theaters, Siegel says. I can name the theaters it played at. At the box office, the movie ended up grossing just $234,540less than Siegel had sunken into it.
And even after Big Fan hit home video, it didnt find a wide audience. On the DVD [cover], they cut me and Kevin to make it look like were actually in the stadium, Oswalt says. But theres no actual football in the movie.
Still, Big Fan has its share of big fans. Its currently at 86 percent on Rotten Tomatoes. This isnt only, or even, a sports movie, Roger Ebert correctly pointed out in his review. Its about leading a life vicariously. Shortly after the movies release, Slates Dana Stevens wrote that it seems destined for a future in the cult canon. The cult never grew very large. But it exists. And its as passionate about Siegels film as Paul is about the Giants.
These days, watching Big Fan is an even more affecting experience than it was 12 years ago. People like Paul Aufiero have always existed. But theyve never been as emboldened as they are now. Imagining Paul, who in the movie can barely use the internet, on social media is both sad and scary. Maybe he wouldve been one of those guys that want to matter on Twitter, but he just doesnt, and all he does is troll celebrities, Oswalt says. The kind of guy that will send horrible things to celebrities, and then when they block them, he takes a screenshot of the block like, Got him.
To his relief, the litigious NFL never got Siegel. Nor did they try. After making a movie about pro football fandom, he went on to tackle other uniquely American phenomena. The Founder, the McDonalds CEO Ray Kroc biopic that he wrote, came out in 2017. Now the former Onion EIC is writing a Hulu limited series based on the Pamela AndersonTommy Lee sex tape scandal.
Siegel, who remains a Steelers die hard, looks back on Big Fan often. But not always fondly. I just remember the mistakes, he says. To this day, two severely irk him. First, the Eagles-Giants season finale in the climactic sequence is played on Monday Night Football. In reality, the last MNF game of the year is held in Week 16, not Week 17. And in the very last scene, when Sal visits Paul in prison, they go over the next years schedule. The Giants AFC opponents play in the North, South, East, and West, an impossibility due to the fact that a clubs annual out-of-conference schedule contains only teams from a single division.
It just gutted me, Siegel says.
Thats the thing about sports: You always remember the painful losses more than the big wins.
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The Cult Sports Movie That Tackled the Underbelly of Fandom - The Ringer
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Romney reintroduces bill banning abortion after 20 weeks of pregnancy – KJZZ
Posted: at 11:46 am
SALT LAKE CITY (KUTV)
Sen. Mitt Romney (R-UT) and other Republican lawmakers are re-introducing a bill to ban abortions after 20 weeks of pregnancy.
Called the Pain-Capable Unborn Child Protection Act, the legislation would criminalize abortions performed after 20 weeks, "the point at which scientific evidence suggests an unborn child is able to feel pain," according to Romney.
According to CDC data, the legislation would apply to the 1.3% of abortions performed in the United States after 20 weeks of pregnancy.
Health care workers, not pregnant women, would face criminal penalties for performing abortions after 20 weeks if the bill were to become law, with the penalty including up to five years in prison.
The legislation does make exceptions in cases of rape, incest, or to protect the life of the mother.
The Pain-Capable Abortion Act has been introduced previously in 2015, when it passed the House but failed in the Senate, Vox reports. It was also on the table again in 2018, when it failed.
RELATED: Sen. Lee sponsors 'Abortion is not Heath Care', other anti-abortion bills as fed policy changes
Reports of the Pain-Capable Unborn Child Protection Act exist as far back as 2015.
Whether or not an unborn child can feel pain at any point in the gestational process remains scientifically unproven, according to multiple scientific publications.
Evidence regarding the capacity for fetal pain is limited but indicates that fetal perception of pain is unlikely before the third trimester," beginning at 27 to 28 weeks after conception according to a 2005 synthesis of available scientific evidence published in the Journal of the American Medical Association.
As recently as 2012, the American Congress of Obstetricians and Gynecologists re-assessed available research and came to the same conclusion.
The Planned Parenthood Association of Utah issued the following statement to 2News regarding Romney and other legislators' re-introduction of the bill:
Health care decisions should be made by patients and their trusted health care provider, not by politicians in the Senate. These bills are designed by politicians to spread misinformation, distort the truth, shame pregnant people and doctors, and ultimately, ban abortion. The American people overwhelmingly support abortion access, and they want a U.S. Senate that works to expand health care, not take it away."
The legislation, led by Sen. Lindsey Graham (R-UT) is also cosponsored by Sens. John Barrasso (R-WY), Marsha Blackburn (R-TN), Roy Blunt (R-MO), John Boozman (R-AR), Mike Braun (R-IN), John Cornyn (R-TX), Tom Cotton (R-AR), Kevin Cramer (R-ND), Mike Crapo (R-ID), Ted Cruz (R-TX), Steve Daines (R-MT), Joni Ernst (R-IA), Deb Fischer (R-NE), Chuck Grassley (R-IA), Bill Hagerty (R-TN), Josh Hawley (R-MO), John Hoeven (R-ND), Cindy Hyde-Smith (R-MS), James Inhofe (R-OK), Ron Johnson (R-WI), John Kennedy (R-LA), James Lankford (R-OK), Cynthia Lummis (R-WY), Roger Marshall (R-KS), Mitch McConnell (R-KY), Jerry Moran (R-KS), Rand Paul (R-KY), Rob Portman (R-OH), James Risch (R-ID), Mike Rounds (R-SD), Marco Rubio (R-FL), Ben Sasse (R-NE), Rick Scott (R-FL), Tim Scott (R-SC), Richard Shelby (R-AL), Dan Sullivan (R-AK), John Thune (R-SD), Thom Tillis (R-NC), Pat Toomey (R-PA), Tommy Tuberville (R-AL), Roger Wicker (R-MS), and Todd Young (R-IN).
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Romney reintroduces bill banning abortion after 20 weeks of pregnancy - KJZZ
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GEN – Genetic Engineering and Biotechnology News
Posted: at 11:38 am
Anniversaries are opportune times to look back at struggles and triumphs, and also to look forward to, well, more struggles and triumphs. The important thing is to stay in the game. And here at GEN, weve been in the game for 40 years, for as long as the word biotechnology has been on peoples lips. To help us mark the occasion, weve invited industry-leading scientists to discuss subjects both enduring and timely. For example, biotech legend Leroy Hood, MD, PhD, draws on his experiences to offer sage advice about realizing scientific and practical breakthroughs. He insists on the value of thinking systemically, working collaboratively, and embracing change. We try, in our own modest way, to engage in these practices and to encourage them in others. Just look at any of our issuesbut especially the current issue, which not only includes articles on a range of exciting technologies, but also a thoughtful editorial contributed by GENs originator and publisher, Mary Ann Liebert. Besides looking back with pride on GENs contributions, she comments on current challenges and anticipates future achievements. GEN will continue, she writes, to identify what you need to know and whom you need to know about.
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GEN - Genetic Engineering and Biotechnology News
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Genetic Engineering – an overview | ScienceDirect Topics
Posted: at 11:38 am
2.08.1 Introduction to Genetic Engineering
With the discovery of DNA as the universal genetic material in 1944 [1] and the elucidation of its molecular structure approximately a decade later [2], the era of DNA science and technology had officially begun. However, it wasnt until the 1970s that researchers began manipulating DNA with the use of highly specific enzymes, such as restriction endonucleases and DNA ligases. The experiments in molecular biology conducted within Stanford University and the surrounding Bay Area in 1972 represent the earliest examples of recombinant DNA technology and genetic engineering [3, 4]. Specifically, a team of molecular biologists were able to artificially construct a bacterial plasmid DNA molecule by splicing and combining fragments from two naturally occurring plasmids of distinct origin. The resulting recombinant DNA was then introduced into a bacterial Escherichia coli host strain for replication and expression of the resident genes. This famous example represents the first use of recombinant DNA technology to generate a genetically modified organism.
In general, genetic engineering (Figure 1) refers to all the techniques used to artificially modify an organism in order to produce a desired substance (such as an enzyme or a metabolite) that is not naturally produced by the organism, or to enhance a preexisting cellular process. As a first step, the desired DNA segment or gene is isolated from a source organism by extracting and purifying the total cellular DNA. The DNA is then manipulated using numerous laboratory techniques and inserted into a genetic carrier molecule in order to be delivered to the host strain. The means of gene delivery is dependent upon the type of organism involved and can be classified into viral and nonviral methods. Transformation (nonviral, for bacteria and lower eukaryotes), transfection (viral and nonviral, for eukaryotes), transduction (viral, for bacteria), and conjugation (cell-to-cell, for bacteria) are all commonly used methods for gene delivery and DNA transfer. Because no method of gene delivery is capable of transforming every cell within a population, the ability to distinguish recombinant cells from nonrecombinants constitutes a crucial aspect of genetic engineering. This step frequently involves the use of observable phenotypic differences between recombinant and nonrecombinant cells. In rare instances where no selection of recombinants is available, laborious screening techniques are required to locate an extremely small subpopulation of recombinant cells within a substantially larger population of wild-type cells.
Figure 1. Basic genetic engineering process scheme including replication and expression of recombinant DNA according to the central dogma of molecular biology.
Although cells are composed of various biomolecules including carbohydrates, lipids, nucleic acids, and proteins, DNA is the primary manipulation target for genetic engineering. According to the central dogma of molecular biology, DNA serves as a template for replication and gene expression, and therefore harnesses the genetic instructions required for the functioning of all living organisms. Through gene expression, coding segments of DNA are transcribed to form messenger RNAs, which are subsequently translated to form polypeptides or protein chains. Therefore, by manipulating DNA, we can potentially modify the structure, function, or activity of proteins and enzymes, which are the final products of gene expression. This concept forms the basis of many genetic engineering techniques such as recombinant protein production and protein engineering. Furthermore, virtually every cellular process is carried out and regulated by enzymes, including the reactions, pathways, and networks that constitute an organisms metabolism. Therefore, a cells metabolism can be deliberately altered modifying or even restructuring native metabolic pathways to lead to novel metabolic activities and capabilities, an application known as metabolic engineering. Such metabolic engineering approaches are often realized through DNA manipulation.
The first genetically engineered product approved by the US Food and Drug Administration (FDA) for commercial manufacturing appeared in 1982 when a strain of E. coli was engineered to produce recombinant human insulin [5]. Prior to this milestone, insulin was obtained predominantly from slaughterhouse animals, typically porcine and bovine, or by extraction from human cadavers. Insulin has a relatively simple structure composed of two small polypeptide chains joined through two intermolecular disulfide bonds. Unfortunately, wild-type E. coli is incapable of performing many posttranslational protein modifications, including the disulfide linkages required to form active insulin. In order to overcome this limitation, early forms of synthetic insulin were manufactured by first producing the recombinant polypeptide chains in different strains of bacteria and linking them through a chemical oxidation reaction [5]. However, nearly all current forms of insulin are produced using yeast rather than bacteria due to the yeasts ability to secrete a nearly perfect replica of human insulin without requiring any chemical modifications. Following the success of recombinant human insulin, recombinant forms of other biopharmaceuticals began appearing on the market, such as human growth hormone in 1985 [6] and tissue plasminogen activator in 1987 [7], all of which are produced using the same genetic engineering concepts as applied to the production of recombinant insulin.
As a result of the sheer number of applications and immense potential associated with genetic engineering, exercising bioethics becomes necessary. Concerns pertaining to the unethical and unsafe use of genetic engineering quickly arose with the advent of gene cloning and recombinant DNA technology in the 1970s, predominantly owing to a general lack of understanding and experience regarding the new technology. The ability of scientists to interfere with nature and alter the genetic makeup of living organisms was the focal point of many concerns surrounding genetic engineering. Although it is widely assumed that the potential agricultural, medical, and industrial benefits afforded by genetic engineering greatly outweigh the inherent risks surrounding such a powerful technology, most of the moral and ethical concerns raised during the inception of genetic engineering are still actively expressed today. For this reason, all genetically modified products produced worldwide are subject to government inspection and approval prior to their commercialization. Regardless of the application in question, a great deal of responsibility and care must be exercised when working with genetically engineered organisms to ensure the safe handling, treatment, and disposal of all genetically modified products and organisms.
As the field of biotechnology relies heavily upon the application of genetic engineering, this article introduces both the fundamental and applied concepts with regard to current genetic engineering methods and techniques. Particular emphasis shall be placed upon the genetic modification of bacterial systems, especially those involving the most famous workhorse E. coli on account of its well-known genetics, rapid growth, and ease of manipulation.
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Exacis Biotherapeutics Announces Key Addition To Its Executive Leadership Team With Dirk Huebner MD Joining As Chief Medical Officer – PRNewswire
Posted: at 11:38 am
CAMBRIDGE, Mass., Jan. 29, 2021 /PRNewswire/ --Exacis Biotherapeutics, Inc., a development-stageimmuno-oncology company working to harness the immune system to cure cancer,today announcedthe addition of Dirk Huebner,MD,as its Chief Medical Officer. Exacis launched in 2020 to develop next generation mRNA-based cellular therapeutics to treat liquid and solid tumors.
Exacis CEO Gregory Fiore MD said, "Dirk is a wonderful addition and a great fit for our management team. His extensive experience in oncology drug development, including antibody related therapies will be instrumental as we build our pipeline to include high performance stealth edited NK and T cells, with and without CARs (ExaNK, ExaCAR-NK and ExaCAR-T). We look forward to Dirk's insights and medical leadership as we build the company and advance our portfolio."
Dr. Huebner joins Exacis from Mersana Therapeutics where he wasthe Chief Medical Officer,oversaw their clinical developmentand helped build thecompany'sclinical infrastructure. Dr Huebnerhas worked in oncology and immuno-oncology drug development and academiafor more than 25 yearsand brings a deep understanding of the needs in the oncology space as well as the ability to successfully deliverproducts to meet those needs.
Commenting on the new role, Dr. Huebner said, "I am thrilled to join the Exacis team and work with best-in-class technology to create innovative, next-generation engineered NK and T cell therapies that have the potential to improve outcomes and treatment experiences for patients with challenging hematologic and solid tumor malignancies."
About Exacis Biotherapeutics
Exacis is a development stageimmuno-oncologycompany focused on harnessing the human immune system to cure cancer. Exacis uses its proprietary mRNA-based technologies to engineer next generation off-the-shelf NK and T cell therapies aimed at liquid and solid tumors.Exacis was founded in 2020 with an exclusive license to a broad suite of patents covering the use ofmRNA-based cell reprogramming and gene editing technologiesfor oncology.
ExaNK, ExaCAR-NK and ExaCAR-T utilize mRNA cell reprogramming and mRNA gene editing technologies developed and owned by Factor Bioscience. Exacis has an exclusive license to the Factor Bioscience technology for engineered NK and T cell products derived from iPSCs for use in oncology and holds all global development and commercial rights for these investigational candidates.
About T and Natural Killer (NK) Cell Therapies
T and NK cells are types of human immune cells that are ableto recognize and destroy cancer cells and can be modified through genetic engineering to target specific tumors.
SOURCE Exacis Biotherapeutics, Inc.
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Deep Learning Shows How Genetic Motifs Conduct the Music of Life – Technology Networks
Posted: at 11:38 am
Our genetic codes control not only which proteins our cells produce, but also to a great extent in what quantity. This ground-breaking discovery, applicable to all biological life, was recently made by systems biologists at Chalmers University of Technology, Sweden, using supercomputers and artificial intelligence. Their research, which could also shed new light on the mysteries of cancer, was recently published in the scientific journal Nature Communications.
DNA molecules contain instructions for cells for producing various proteins. This has been known since the middle of the last century when the double helix was identified as the information carrier of life.
But until now, the factor which determines what quantity of a certain protein will be produced has been unclear. Measurements have shown that a single cell can contain anything from a few molecules of a given protein, up to tens of thousands.
With this new research, our understanding of the mechanisms behind this process, known as gene expression, has taken a big step forward. The group of Chalmers scientists have shown that most of the information for quantity regulation is also embedded in the DNA code itself. They have demonstrated that this information can be read with the help of supercomputers and AI.
You could compare this to an orchestral score. The notes describe which pitches the different instruments should play. But the notes alone do not say much about how the music will sound, he explains.
Information for the tempo and dynamics of the music are also required, for example. But instead of written instructions such asallegroorfortein connection with the notation, the language of genetics spreads this information over large areas of the DNA molecule. Previously, we could read the notes, but not how the music should be played. Now we can do both, states Aleksej Zelezniak.
Another comparison could be that now we have found the grammar rules for the genetic language, where perhaps before we only knew the vocabulary.
What then is this grammar, which determines the quantity of gene expression? According to Aleksej Zelezniak, it takes the form of reoccurring patterns and combinations of the four notes of genetics the molecular building blocks designated A, C, G and T. These patterns and combinations are known as motifs.
The crucial factors are the relationships between these motifs how often they repeat and at exactly which positions in the DNA code they appear.
We discovered that this information is distributed over both the coding and non-coding parts of DNA meaning, it is also present in the areas that used to be referred to as junk DNA.
The researchers tested the method in seven different model organisms from yeast and bacteria to fruit flies, mice, and humans and found that the mechanism is the same. The discovery they have made is universal, valid for all biological life.
According to Aleksej Zelezniak, the discovery would have not been possible without access to state-of-the-art supercomputers and AI. The research group conducted huge computer simulations both at Chalmers University of Technology and other facilities in Sweden.
This tool allows us to look at thousands of positions at the same time, creating a kind of automated examination of DNA. This is essential for being able to identify patterns from such huge amounts of data.
Jan Zrimec, postdoctoral researcher in the Chalmers group and first author of the study, agrees, saying:
With previous technologies, researchers had to tell the system which motifs in the DNA code to search for. But thanks to AI, the system can now learn on its own, identifying different motifs and motif combinations relevant to gene expression.
He adds that the discovery is also due to the fact they were examining a much larger part of DNA in a single sweep than had previously been done.
The new knowledge could also make it possible to better understand how mutations can affect gene expression in the cell and therefore, eventually, how cancers arise and function. The applications which could most rapidly be significant for the wider public are in the pharmaceutical industry.
It is conceivable that this method could help improve the genetic modification of the microorganisms already used today as biological factories leading to faster and cheaper development and production of new drugs, he speculates.
Reference: Zrimec J, Brlin CS, Buric F, et al. Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure. Nat Commun. 2020;11(1):6141. doi:10.1038/s41467-020-19921-4.
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
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Modified crops modified perspective – Varsity Online
Posted: at 11:38 am
Genetically modified crops could provide a solution to the world hunger problem, but how serious are the risks for our ecosystems?pixnio.com
Just over 20 years ago, agroup of environmental activistsdestroyed experimental GM maize being grown on a Norfolk farm in a landmark act of protest, which brought genetically-engineered crops into the public eye, and was followed by global demonstrations and the adoption of severely restrictive legislature by the EU. Whilst some of the major food-producing countries of the world have become more open to genetically-engineered crops, public attitudes still remain largely hostile. In the UK, 40% of adults surveyed in 2012 believed the government should not be endorsing the use of genetically-engineered crops. These expressions of distrust largely stem from a lack of understanding surrounding genetically-engineered crops asurvey in 2019 found that only 32% of UK adults felt informed about GM crops, and misinformation spread by anti-GMO campaigns has done nothing to alleviate this.
In reality, the facts of genetic engineering are far simpler than such campaigns would make them appear.
In reality, the facts of genetic engineering are far simpler than such campaigns would make them appear. Earlier efforts mainly relied on the use of the bacterium Agrobacterium tumefaciens to introduce foreign DNA into the genome of a plant embryo, and the use of antibiotic-resistance marker genes to select transformed plants. This initially gave rise to fears of spreading antibiotic resistance through genetic engineering, although these marker genes have generally been replaced by plant-derived markers in the transformation process.
With the advent of CRISPR-Cas9 technology, however, engineering of plant genomes has become significantly easier. CRISPR-Cas9 utilises a mechanism found in prokaryotic immune systems, in which characteristic DNA sequences of potentially harmful bacteria are stored in a cluster of sequences, known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). These sequences can be transcribed and used to guide the DNA-cleaving activity of the Cas9 protein in genetic engineering, guide RNA for a locus in the plant genome is used to target cuts. CRISPR-Cas9 technology is proving crucial in genetic engineering, thanks to the ease with which endogenous genes can be edited without inserting foreign DNA, which helps the public image of genetically-engineered crops.
But whilst health risks of genetically-engineered crops on the market have been rigorously examined and disproved, these crops are not without their faults. One of the greatest risks posed by transgenic crops is the potential for transgene flow into wild crop relatives, potentially conferring pest or herbicide resistance. Whilst experimental crops are isolated to reduce this risk, this is often not possible for commercial crops, and evidence suggests some small-scale spread of transgenic traits occurring around fields of transgenic crops. The difficulty in preventing transgene spread, however, is that the methods used for instance, pollen sterility can prevent farmers from harvesting and replanting seeds, forcing them to repeatedly buy expensive seed from the developers. This may create a financial barrier to the benefits of such crops for those who might need them most.
Yet with the world population set to hit 8.1 billion by 2025, global solutions are now required to meet the challenges of feeding the growing population in an increasingly adverse climate. Given that roughly 37% of habitable land area is already used in agriculture, the capacity for further expansion is limited, and so increasing the efficacy of crop growth is therefore needed to meet demand. This will likely require the rapid improvement of crops through genetic engineering, with advances in adapting existing plant responses to abiotic stress for instance, increasing the production of osmoprotectants that protect protein structure in drought conditions likely to prove crucial in improving crop productivity whilst minimising strain on land and water resources.
Despite the risks, the improving reliability of transgeniccrop isolation and the benefits of genetically-engineered crops make a compelling case for extending their use. This is especially true for countries experiencing massive population growth, which often also bear the brunt of climate change so what is hindering this?
You dont have to look any further than the case of Golden Rice for the answers. The poster child of the genetically-engineered crop movement, Golden Rice was initially developed in the early 2000s as a transgenic rice strain with aVitamin A content sufficient to provide 80-100% of the RDI in a single cup of rice. This was a solution developed to combat the lack of the vitamin in the diets of many developing countries, with a third of children worldwide estimated to be Vitamin A deficient, leaving them at high risk of death or blindness. Given repeated testing proving both the efficacy and the safety of the rice, it would seem a foregone conclusion that its use in filling the coverage gaps in vitamin supplement distribution would be widely approved. Yet to this day, not a single crop of Golden Rice has been grown outside of experimental trials.
The reasons for this can be traced back to the legislation governing genetically-engineered crops, such as the Cartagena Protocol, which prevents the introduction of new biotechnology should it pose a risk to human or environmental health. Despite very low rates of gene flow from cultivated rice to wild species, and limited evidence to suggest the transgene would persist in wild populations, this protocol was used to ban the introduction of Golden Rice in the EU, which, in conjunction with Greenpeace campaigns, fed fears surrounding the unsafe nature of the crop. However, rulings in recent years appear to be turning the tide; earlier approval from the health authorities of the US, Australia, New Zealand and Canada has been followed by approval in the Philippines and impending approval in Bangladesh, which hopefully signals the start of Golden Rice growth in countries affected by Vitamin A deficiency.
The challenge for the future lies mainly in the general publics understanding and perception of genetic engineering
Although progress is being made in the introduction of genetically-engineered crops, the future of research and development in crop engineering is looking dim. With recent reclassification of GM crops by the EU to include gene-edited crops, those edited using CRISPR-Cas9 are now as severely restricted as transgenic crops. This comes at a time when effective solutions for food production are needed more than ever, and so immediate action is needed if genetically-engineered crop development is to continue. The challenge for the future lies mainly in the general publics understanding and perception of genetic engineering; if improved, this could have considerable influence in producing a more considered approach to GM crop legislation cutting the red tape and allowing the benefits of genetically-engineered crops to reach those most in need.
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Their Goal: Meat That’s Better Than Meat | Tufts Now – Tufts Now
Posted: at 11:38 am
There are plenty of reasons to want to shift away from eating meat: its better for the planet and certainly better for animals that would otherwise be eaten. But meat is still a big draw, both in the U.S. and increasingly in medium-income countries like China.
At the Tufts School of Engineering, a team of scientists led by Professor David Kaplan is exploring another avenue to feed this trendmeat grown directly from animal cells. It could be the start of an entirely new agricultural industryas humane and green as plant-based meat substitutes, but providing taste, texture, and nutrition that is even closer to the experience of eating real meat.
The technology is already familiar to cell biologistsgrowing and harvesting cells from a single sample of tissue from a live anesthetized animal, but doing it in ways that may help the cells transform into something similar to the muscle tissue people enjoy eating from beef, chicken, and fish, including shrimp and scallops.
Meat from animals contains connective tissue, vascular networks, fat, and other cell types, as well as blood, biological fluids, and a complex mix of proteins and sugars, all of which contribute to the unique taste and texture of the meat. Replicating that structure and content is the technical challenge that the Tufts team is working on using the tools of tissue engineering.
A variety of flavors and textures can be achieved by growing different types of cells together, like skeletal muscle, fat cells and fibroblasts (the most common type of cell in connective tissue), adding nutrients to the surrounding media (the soup in which the cells grow), or using genetic modification to add components that not only introduce flavors, but can modify color or even improve on the nutritional quality of natural meat.
Andrew Stout, a doctoral student in biomedical engineering, has explored adding myoglobin to the cell growth media, for example. Myoglobin, a natural component of muscle, is a protein that carries iron and oxygen, and is associated with the bloody flavor of meat. He found that its addition to the mix helps improve the color of the cell mass, and even enhanced the growth rate of the meat substitute.
Stout has also been working to enhance the nutritional content of cell-based meat. In a recent journal publication, he reported how he had modified muscle cells from cows by genetically adding enzymatic machinery to produce the antioxidants phytoene, lycopene, and beta-carotene, normally found in plants.
Think of it as a way to make cell-based meat more plant-like in the healthy nutritional components it offers. Adding beta-carotene, for example, could have protective effects against colorectal cancer, which tends to be more prevalent among those with a high intake of red meat. Another benefit of this type of metabolic engineering is that the antioxidants could improve the quality and shelf-life of the meat.
How far can they take this nutritional engineering? I think other nutrients would definitely work, said Stout. Thats one of the things that I am the most excited about. Putting plant genes into mammalian cells is pretty un-travelled scientific territory, and so theres a lot of space to explore other nutrients, flavor, and color compounds. In addition, he adds, the cell-based meat can be engineered as a therapeutic food.
Most cell-based approaches have emulated processed meat such as hamburger, sausage, and nuggets. Replicating the appearance and texture of whole cuts of meat, like steak, is a different kind of challenge.
Tissue engineering experts in the Kaplan lab bring a lot of experience to the task of aligning cells and creating fibers resembling real meat structure, using things like mechanical tension and micropatterned substrates to help align cells into fibers.
Natalie Rubio, a Ph.D. student in biomedical engineering, found that switching from cows to caterpillars as a source of cells can have some advantages. The muscle and fat stem cells originating from the eggs of the tobacco hornworma beefy little caterpillarcan be used to generate tissue that resembles other invertebrates that were used to eating, like shrimp and scallops.
A vast amount of knowledge has already developed around large scale invertebrate cell culture, since insect cells are widely used in the production of pharmaceuticals. Suspended in a liquid medium, they tend to grow to very high density and have simpler requirements for maintenance and growth. Yields could be greater and production costs lower than from mammalian cells.
But Rubio explains that there is a very important step remaining to transform a soup of cells into something resembling real meatproviding a scaffold to shape and orient the cells.
The scaffold is the backbone of the meatit provides structure and texture, said Rubio. If we did not have that support structure, the meat would just look like slime.
Rubio generates scaffolds from chitosana polymer found in a closely related form (chitin) in exoskeletons such as crab shells and fungi. Chitosan is a great material to make scaffolds from because it is edible, abundant, and inexpensive, she said.
Chitin can be isolated from fungi and easily converted to chitosan and then formed into films, fibers, or sponges to act as scaffolding for cell culture. Rubio grows insect muscle and fat cells on the chitosan scaffolds to generate small, structured meat constructs.
Kaplans lab has been a hub and catalyst for cellular agriculture research and development in the academic sector for many years, he said. That continues with an annual course for undergraduates on cellular agriculture, which is again being offered this spring semester.
Cell-based meat has not yet been commercialized, but the first cultured beef burger was produced by Maastricht University in 2013, and a number of start-up companies are now working to create new products to sell.
Alumni from our group have fanned out across the globe to help create the foundation of a nascent cell-based agricultural industry, Kaplan said. They include Laura Domigan, who is a principal investigator at University of Auckland; research scientist Amanda Baryshyan at Gloucester Marine Genomics Institute; Ryan Pandya, CEO of Perfect Day Foods; Viktor Maciag, head of tissue engineering at Mission Barns; and Robin Simsa, CEO of Legendary Vish.
Mike Silver can be reached at mike.silver@tufts.edu.
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Animal Genetics Market Forecast to 2027 – COVID-19 Impact and Global Analysis By Product, Genetic Material, and Services and Geography. -…
Posted: at 11:38 am
New York, Jan. 26, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Animal Genetics Market Forecast to 2027 - COVID-19 Impact and Global Analysis By Product, Genetic Material, and Services and Geography." - https://www.reportlinker.com/p06010023/?utm_source=GNW However, the market is likely to get impacted by the limited number of skilled professionals in veterinary research and stringent government regulations for animal genetics during the forecast period.
The branch of genetics that deals with the study of gene variation and inheritance in companion, domestic and wild animals is called as animal genetics.Animal genetics are used for genetic trait testing, DNA testing, and genetic disease treatment.
Animal genetics is one of the best mainstays of livestock development (alongside animal nutrition, animal health, and husbandry concerns such as housing). According to the Food and Agriculture Organization of the United Nations, it is a wide field, ranging from characterization to maintenance to genetic improvement, and involves activities at local, national, regional, and global scales.Increasing population and rapid urbanization across the world has resulted in growing preference for animal derived food products such as dairy products and meat that contain high protein.The demand for animal derived proteins and food products, which, in turn drives the growth of animal genetics market.
Growing focus on developing superior animal breeds using genetic engineering to obtain high reproduction rates for large-scale production of modified breeds is expected to drive animal genetics market during the forecast period.Based on product, the market is segmented into poultry, porcine, bovine, canine, and others.The porcine segment held the largest share of the market in 2019, whereas the same segment is anticipated to register the highest CAGR in the market during the forecast period.
Growth of this segment is attributed to rise in production of porcine and increase in pork consumption across the globe.Based on genetic material, the market is segmented into semen and embryo. The embryo segment held the largest share of the market in 2019, and the semen segment is anticipated to register the highest CAGR in the market during the forecast period.COVID-19 pandemic has become the most significant challenge across the world.This challenge would be frightening, especially in developing countries across the globe, as it may lead to reducing imports due to disruptions in global trade, which further increases the shortages of meat and dairy product supplies, resulting in a considerable price increase.
Asian countries such as China, South Korea, and India are severely affected due to COVID-19 outbreak.The World Health Organization, Food and Drug Administration, American Pet Products Association, American Veterinary Medical Cattle Health, and Welfare Group for Disease Control and Prevention are among the major primary and secondary sources referred for preparing this report.Read the full report: https://www.reportlinker.com/p06010023/?utm_source=GNW
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Restart the ripening clock – Good Fruit Grower
Posted: at 11:38 am
(TJ Mullinax/Good Fruit Grower photo illustration)
For more than a decade, Washington State University geneticist Amit Dhingra has been trying to figure out the underlying genetics of pear ripening in order to design postharvest products that could deliver consistent fruit quality.
A series of research projects that began with trying to understand the seemingly unpredictable impacts of 1-MCP (1-methylcyclopropene, which blocks ethylene receptors) on pears and find postharvest products that would deliver consistent fruit quality are now starting to fit together like the pieces of a puzzle, Dhingra said, with new tools to spur ripening and a genetic understanding of how and why they work.
A new Specialty Crop Block Grant from the Washington State Department of Agriculture will help Dhingra and a commercial partner, Crunch Pak of Cashmere, to commercialize the use of the ripening tools on 1-MCP-treated fruit in a sliced pear application that Dhingra believes could create a new pear market.
This is a unique niche where 1-MCP-treated fruit can be put into this category, Dhingra said. Before we replant the entire acreage of pears, we need to bring money into the industry. A toolkit of 1-MCP plus the ripening compound can make that possible.
On the research front, Dhingra calls pears a great teacher for studying which genes control fruit ripening.
We wanted to understand what is happening in pears during conditioning, and most of the previous studies looked at ethylene only, Dhingra said. Ripening fruit produce ethylene, which then drives most of the ripening process in climacteric fruit fruit that continues to ripen after harvest such as pears. Many Anjou pears are now ethylene-treated to promote more uniform ripening just before delivery to customers. But, as Dhingras team found, ethylene doesnt tell the whole story for European pears.
When we started looking at a whole suite of genes beyond ethylene, to our surprise we found there is a metabolic pathway that gets activated, preclimateric, in pears, he said. Preclimateric refers to the fruit before the surge in ethylene that occurs during ripening.
Looking at dozens of genes in freshly picked and ripe pears, to see which played a role in ripening, Dhingra and his graduate students, Seanna Hewitt and Christopher Hendrickson, zoomed in on some unexpected gene activity in whats known as the alternative oxidase pathway that started in both Bartlett and Anjou pears during cold conditioning.
Pears, when they are harvested, they dont have the entire energy currency they need to drive the starch conversion to sugar, Dhingra said. This alternative respiratory pathway produces the energy to kick-start the ripening pathway.
The cold temperatures that pear packers have long known are key to successful ripening appear to kick-start this AOX pathway, which then activates the better understood ethylene-driven ripening process. Thats different than most other climacteric fruits, where the AOX pathway exists but occurs after ethylene surges.
However, cold alone doesnt spur the AOX into action. Once they understood the pathway involved, the researchers went searching for chemical compounds that might also trigger it, Dhingra said. They found one called glyoxylic acid, about five years ago.
Since then, theyve tested it, patented it and published several scientific papers proposing the underlying mechanisms. That genetic understanding could someday be used to inform breeding or genetic engineering to target pear ripening.
But the road from promising research to commercial use is long.
Longtime pear research advisor Bob Gix said hes excited about Dhingras findings but also cautious, considering the challenges of proving new tools in a commercial setting.
These new fundamental understandings represent a fantastic building block for ripening in pear fruit with the goal of delivering a more consistent high-quality product to the consumer, Gix said. The greatest endorsement of these discoveries will be common industry use. I do not believe we are there yet.
On the commercial front, the most promising application so far seems to be in sliced pears, where exposed flesh treated with glyoxylic acid consistently overcomes the ripening pause created by 1-MCP. Ray Schmitten, a grower serving on an industry research advisory committee, suggested the idea.
Everybody would like to see (sliced pears), but its not as easy as we would like it to be, Schmitten said, reflecting on many years of industry-funded research into the feasibility of sliced pears. The warehouse he works for, Blue Star Growers, provides fruit to Dhingras research trials.
Its something obvious in hindsight, but much to our surprise, we saw a huge jump in ethylene when we applied (glyoxylic acid) to sliced 1-MCP fruit, Dhingra said. It would allow packers to treat and store pears for subsequent slicing and ripening so the consumers get the convenient fruit at peak quality.
With funding from the Fresh Pear Committee, Dhingra partnered with Crunch Pak several years ago to test out the viability of the sliced pear application, which was well received by consumers in taste tests, he said. Crunch Pak, which primarily markets sliced apple products, did not return requests for comment.
But the team also discovered that packaging plays a significant role in the quality of the final product, Dhingra said. Modified atmosphere plastics regulate gas exchange to keep produce fresh longer.
In the modified atmosphere bag world, you have to find a bag that corresponds to the respiration rate of the fruit in question, Dhingra said. He found that in one bag, fruit spoiled too quickly, and in another, the fruit moved toward ripening too slowly.
The new grant will enable testing of four different modified atmosphere bags to find the Goldilocks fit for sliced Anjous, he said, as well as dialing in the correct amount of the ripening compounds to apply for consistent, high-quality results.
Part of the challenge in commercializing the glyoxylic acid is that for whole pears, the amount needed depends on the amount of 1-MCP the fruit was treated with. Thats a surprisingly hard thing to measure, as warehouses treat pears with 1-MCP in parts per billion, as opposed to the parts-per-million rates common in apples.
Its a technical challenge. When you are looking at a parts-per-billion application changing physiology, any small variation can have a significant effect, he said.
The use of 1-MCP has become controversial in pears in recent years, with some packing houses swearing off it and others working with longtime manufacturer AgroFresh to dial in the dosing to account for growing conditions, harvest timing and storage goals to optimize performance, commercial development manager Fernando Edagi said. 1-MCP is not a one-size-fits-all solution.
Schmitten, who took a strong stand against overuse of 1-MCP, now says the product has its place in long-term storage, and applications such as pairing with this novel ripening compound could be another beneficial use.
Dhingra hopes his new compound can help packers take advantage of the benefits of 1-MCP and reduce the drawbacks, saying it basically exploits this back door that nature showed us to use these metabolic compounds to overcome the limitations of 1-MCP.
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