Monthly Archives: December 2019

Cell Biology

The Science News that Shaped 2019 – The Scientist

Discovery of a new T cell

With all the extensive investigations scientists have conducted of the human immune system over the past century, it is astonishing that there are still new cell types to be found. Yet in May, researchers described a hybrid of B and T cells, which they named dual expresser (DE) cells, in people with type 1 diabetes. We think [the DE cell peptide may play] a very major role during the initial phase of the disease, Abdel Hamad, an immunologist at Johns Hopkins University School of Medicine and the senior author of the study, told The Scientist at the time.

That same month, scientists also reported that humans natural killer cells, thought to form the innate immune response, can also keep memories of past encounters with offending antigens, much like the adaptive immune response does. The discovery challenges the basic dogma of how these cells functionanother reminder there is still so much unknown even in our own blood.

Measles, Ebola, and polio flared up in 2019. Cases of measles in the US were the highest since the virus was declared eradicated in America in 2000, and they have been soaring in Europe and elsewhere. Public health officials say insufficient immunization, fueled by anti-vaccine sentiment, is to blame. All the while, scientists continued to learn about the virusand just how dangerous it is. In October, researchers reported that infection with the virus that causes measles appears to leave the immune system vulnerable to infections by other pathogens.

Thousands of people died of measles this year in Democratic Republic of Congo, where an outbreak of Ebola has also been ongoing since the 2018. Violence in the region has hampered efforts to get the Ebola epidemic under control, but newly developed drugs and vaccines administered this year may help slow Ebolas spread.

Polio will soon have another vaccine to contend with as researchers have developed one to designed to counteract the failure of an older vaccine that allowed the virus to continue to circulate and eventually revert to virulence. Such vaccine-derived polio cases have now become more common than those caused by the wild virus, but the new vaccine, which is genetically engineered to avoid such reversion, is set to be deployed in 2020.

The long-term price we pay for having a chilly research environment far exceeds that of the few ideas stolen from us.

Alice Huang, CaltechFears of espionage

Federal science agencies have been cracking down on researchers who violate the rules for relationships with foreign governments, in an effort to prevent other countries from stealing US intellectual property. An eye doctor at the University of California, San Diego, cancer researchers at MD Anderson Cancer Center, geneticists at Emory University, and the leaders of Moffitt Cancer Center in Florida are among those have lost their jobs because of their ties to China.

As the US government moves to strengthen defenses against espionage, researchers have voiced concerns of racial profiling, specifically, that Chinese and Chinese-American scientists will be unfairly scrutinized. Writing to The Scientist in March, Caltech biologist Alice Huang says, The long-term price we pay for having a chilly research environment far exceeds that of the few ideas stolen from us.

To avoid legal issues, researchers from Spain and the US developed the first human-monkey chimeras in China, a Spanish newspaper reported in July. The embryos development was stalled after a few weeks, but the scientists would like to grow animals whose organs could be harvested for human transplant, a goal at least one expert finds impractical. I always made the case that it doesnt make sense to use a primate for that. Typically they are very small, and they take too long to develop, Pablo Ross, a veterinary researcher at the University of California, Davis, told MIT Technology Review.

While still illegal to pursue in the US using federal research funds, human-animal chimera projects got the regulatory green light in Japan last spring. Its good that they now allow people to do human-animal [chimera embryos] with species like pigs and sheep, Sean Wu, a developmental biologist at Stanford University, told The Scientist in April. But human-primate chimeras are a different, um, animal. Theres just too many things we dont know about when you try to chimerize two species that are so close to each other, like humans with nonhuman primates.

Teeth of the newly named hominin Homo luzonensis

CALLAO CAVE ARCHAEOLOGY PROJECT

Speaking of new humans, scientists described an entirely new species of Homo, H. luzonensis, this year. The first bone of our newly named cousin was originally dug up in Callao Cave in the Philippines in 2007, but back then it wasnt clear who exactly it belonged to. The discovery of more bones and teeth led scientists to conclude that the individuals were a distinct species. Its fantastic news. Its not every day you get to name a new species within the human family tree, Michael Petraglia, a professor of human evolution and prehistory at the Max Planck Institute for the Science of Human History who wasnt involved in the study, told The Scientist at the time.

The friendships that convicted sex offender Jeffrey Epstein had forged with scientists, and the money he gave them for research, caused an uproar this year. Scholars quit their jobs at MIT in protest while some universities pledged to redirect the money to charitable causes.

At the same time, the Sackler family (of oxycontin-maker Purdue Pharma) came under heightened scrutiny for their role in the opioid epidemic. The Sacklers have been big donors to biomedical research over the years, and Tufts University recently decided to strip the Sackler name from its campus buildings.

Thanks to the work of survivors and activists, #metoos momentum carried through in 2019. Scientific conference organizers were forced to reflect on their policies for protecting attendees, especially in the archaeology field after a known harasserbanned from his own campus where he had been a professor for decadesshowed up at the Society for Archaeology meeting in Albuquerque this year. Victims of David Yesner were present at the meeting and alerted staff, but the societys response was inadequate, causing a prompt backlash on social media and a longer-term reckoning that has since resulted in a more-solidified policy. Members of the SAA voted to allow board members to ban convicted harassers from attending meetings.

The glycan (upper left) and RNA (lower right) are connected by an unknown intermediary in this possible structure of glycoRNA.

RYAN FLYNN

Although still in preprint form, results published this fall introduced a new aspect to cell biology: glycoRNAs, or noncoding RNA strung with complex sugars called glycans. Glycans are normally sequestered in the endoplasmic reticulum and Golgi bodies, away from RNA in the cytoplasm and nucleus. There really is no framework in biology as we know it today that would explain how RNA and glycans could ever be in the same place at the same time, much less be connected to each other, senior author Carolyn Bertozzi, a chemical biologist at Stanford University, told The Scientist in October. Whatever it is, its a completely unknown biology. Expect to see more insight into this mysterious new cellular entityits function, its structure, and its prevalence.

A wave of pulmonary illnesses and deaths related to vaping swept across the US this year. It wasnt clear to clinicians at first why these cases were appearing, but months of sleuthing led investigators to conclude that vitamin E acetate added to products, especially counterfeit liquids containing THC, was a possible culprit. The Centers for Disease Control and Prevention is continuing to investigate, as more ingredients may be to blame.

Researchers doubled DNAs alphabet this year with the development of two new synthetic nucleotides, adding to two created previously, leading to what they call a hachimoji DNA molecule composed of four synthetic and four natural bases. The DNA successfully transcribed hachimoji RNA using a bacteriophage RNA polymerase. This is really an exciting paper . . . a true engineering feat, Northwestern Universitys Michael Jewett, who was not involved with the research, wrote in an email to The Scientist in February.

Kerry Grens is a senior editor and the news director of The Scientist. Email her at kgrens@the-scientist.com.

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The Science News that Shaped 2019 - The Scientist

Cell Biology

What is ‘dopamine fasting’? How some are trying to change their brains – TODAY

As interest in intermittent fasting keeps growing, a completely different type of fasting trend is coming out of Silicon Valley. Followers of "dopamine fasting" believe that if they deprive themselves from anything stimulating devices, movies, TV, light or even other people they can alter the levels of dopamine in their bodies and reset their brains.

On the surface, it's a life hack that sounds like a good idea: try to modify the dopamine chemical known as one of the "happy hormones" in the body simply by unplugging from devices and stepping away from activity.

"Dopamine fasting is like, 'I'm getting off my devices so I can feel more,'" Dr. Zach Freyberg, an assistant professor of psychiatry and cell biology at the University of Pittsburgh, told TODAY. "It's doing things that are that are meant to keep you sensitized to the world around you."

To fast, followers say they avoid things they enjoy, which can include mobile devices, sex, social media, entertainment, shopping, gambling, exercise, food and alcohol, for a set period of time. Some might even avoid eye contact or chats during that time.

The goal avoiding stimulation in the present, in order to be happier later. For example, love online shopping? During a fast, you'd skip it.

In a way, it's like meditation where people spend time without outside excitement. But this type of fasting is tailored to what specifically causes your dopamine to spike, whether it's red wine, Snapchat or Christmas movies.

Sounds simple, right? Not really.

Your brain is always working. Your neurotransmitters, like dopamine, are always working, Madelyn Fernstrom, a neuroscientist and NBC News health and nutrition editor, told TODAY.

While dopamine fasting focuses on the molecule's role as a neurotransmitter in the brain, dopamine does a lot of heavy lifting throughout the body.

Dopamine is something that's inside of our bodies that our bodies make, Freyberg said. In the brain, dopamine is responsible for lots of important brain functions. You need it to help control mood, you need that to feel a sense of satisfaction and reward.

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People often think of it as the hormone of excitement and novelty seeking, said Dr. Amit Sood, executive director of the Resilient Option, and former professor of medicine at Mayo Clinic.

This means people experience a surge of it when they try something new or anticipate something. Some of what Silicon Valley sells causes dopamine spikes.

A lot of social media is driven by dopamine, he said. Youre just chasing it.

But dopamines role is much more complex. It also helps the brain control movement and exists in other parts of the body, regulating insulin, aiding digestion, managing kidney function and maintaining blood pressure.

Its kind of like an air traffic coordinator. It controls and coordinates the functions of a lot of different organs, a lot of different parts of the body, to make sure they work harmoniously, Fryberg explained.

Not having enough dopamine causes real problems. Parkinsons disease, for example, is a disorder of dopamine, Fryberg said.

The body absolutely needs to make that dopamine because it needs to control the life support systems, he said.

In some ways, eating and exercising can influence dopamine production, but not in the way that dopamine fasting fans think.

When you eat, the amount of dopamine in your blood stream temporarily goes up because that helps control insulin, Fryberg said. There's more and more evidence that exercise can help in Parkinson's patients preserve the amount of dopamine in the brain.

Beyond that that's all we know, he said.

The experts agree that even if the name is an oversimplification of how brain chemistry works, the concept behind dopamine fasting is positive. What "fasters" are truly proposing is taking a break from stimulation and being mindful both healthy practices.

There is no downside, unless you believe you are having an immediate impact on your brain chemistry, Fernstrom, a nutrition scientist, said. It is mistake to think that a short-term behavior of any kind is going to be having an impact on your brain.

Whats more, unplugging and spending time without stimulation might have an opposite effect than anticipated.

Meditation has been shown to increase dopamine in the brain reward activity center, Sood said.

While meditation and avoiding devices is beneficial, Sood encourages people to think of it as adding something to life not subtracting.

It is very difficult to empty your life of something, he said. I tried emptying my mind and it doesnt work. It is not about emptying it. Its about filling it with the right things.

That's why he suggests that people think of something positive while stepping away from devices and overactivity.

If you meditate on gratitude or compassion or kindness it will be more effective, Sood said.

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What is 'dopamine fasting'? How some are trying to change their brains - TODAY

Cell Biology

Metabolic dysregulation: origins of neurodegenerative disease – Health Europa

A new study, published in the journal Neuron, implicates metabolic dysregulation in neurodegenerative diseases leading to altered calcium homeostasis in neurons as the underlying cause of cerebellar ataxias.

This study not only tells us about how SCA7 begins at a basic mechanistic level, but it also provides a variety of therapeutic opportunities to treat SCA7 and other ataxias, said Al La Spada, MD, PhD, professor of Neurology, Neurobiology, and Cell Biology, at the Duke School of Medicine, and the studys senior author.

SCA7 is an inherited neurodegenerative disorder that causes progressive problems with vision, movement, and balance. Individuals with SCA7 have CAG-polyglutamine repeat expansions in one of their genes; these expansions lead to progressive neuronal death in the cerebellum. SCA7 has no cure or disease-modifying therapies.

La Spada and colleagues performed transcriptome analysis on mice living with SCA7. These mice displayed down-regulation of genes that controlled calcium flux and abnormal calcium-dependent membrane excitability in neurons in their cerebellum.

La Spadas team also linked dysfunction of the protein Sirtuin 1 (Sirt1) in the development of cerebellar ataxia. Sirt1 is a master regulator protein associated both with improved neuronal health and with reduced overall neurodegenerative effects associated with aging.La Spadas team observed reduced activity of Sirt1 in SCA7 mice; this reduced activity was associated with depletion of NAD+, a molecule important for metabolic functions and for catalysing the activity of numerous enzymes, including Sirt1.

When the team crossed mouse models of SCA7 with Sirt1 transgenic mice, they found improvements in cerebellar degeneration, calcium flux defects, and membrane excitability. They also found that NAD+ repletion rescued SCA7 disease phenotypes in both mouse models and human stem cell-derived neurons from patients.

These findings elucidate Sirt1s role in neuroprotection by promoting calcium regulation and describe changes in NAD+ metabolism that reduce the activity of Sirt1 in neurodegenerative disease.

Colleen Stoyas, PhD, first author of the study, and a postdoctoral fellow at the Genomics Institute of the Novartis Research Foundation in San Diego, said: Sirt1 has been known to be neuroprotective, but its a little unclear as to why.

Tying NAD+ metabolism and Sirt1 activity to a crucial neuronal functional pathway offers a handful of ways to intervene that could be potentially useful and practical to patients.

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Metabolic dysregulation: origins of neurodegenerative disease - Health Europa

Cell Biology

Vaping May Increase the Risk of Chronic Respiratory Disease – Scientific American

A recent outbreak of deadly lung illnesses linked to vaping has put the practice in health professionals and regulators crosshairs. Now the first longitudinal population-based study of e-cigarette use in a representative sample of U.S. adults suggests it increases the risk of many chronic lung illnesses, tooespecially when combined with smoking combustible tobacco.

Most of the media coverage of vaping has focused on the short-term, or acute, health impacts. More than 2,500 cases of e-cigarette, or vaping, product useassociated lung injury (EVALI) have been reported across all 50 states and the District of Columbia, as well as in Puerto Rico and the U.S. Virgin Islands; 54 deaths have been confirmed to date. Black market productscontaining THC (the primary psychoactive ingredient in marijuana were the mostly commonly reported by EVALI patients, buthealth authorities have not ruled out risks of lung injury from other vape products.*

The new research suggests that e-cigarettes may also cause long-term health problems. The study, published this week in the American Journal of Preventive Medicine, found that people who reported using the devices were more likely to develop lung illnesses such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema or asthma. E-cigarettes have been touted as a harm-reduction method for helping smokers quit, and the new findings could challenge that.

One of the problems that we've had with the whole e-cigarette debate is its asking this abstract question: Are e-cigarettes less dangerous than cigarettes? The answer to that is: if youre a never smoker who never vaped, the e-cigarettes arent as bad as the cigarettes, says study co-author Stanton Glantz, a professor of medicine at the University of California, San Francisco. But in the real world, most adult e-cigarette users are dual [e-cigarette and combustible tobacco] usersand thats worse than [just] smoking.

Like conventional cigarettes, e-cigarettes contain nicotine and various toxic substances that have been shown to disrupt lung function. But e-cigarettes also contain material such as propylene glycol, flavorings such as diacetyl (for a butter taste) and cinnamaldehyde (for cinnamon), as well as heavy metals. Previous studies in animals have shown that exposure to e-cigarette vapor is linked to lung inflammation and depressed immune activity, and repeated exposure appears to cause lung damage that resembles COPD. Most of the studies in humans have been observational, but they have found an association between e-cigarette use and respiratory disease. And a longitudinal study of people with COPD found that smoking e-cigarettes was linked to exacerbations of the disease and a faster decline.

In the new study, Glantz and his U.C.S.F. colleague Dharma Bhatta analyzed data from the Population Assessment of Tobacco and Health (PATH) Study, a longitudinal study of adult tobacco use and health in the U.S. They used data collected from three consecutive time points, or waves, between 2013 and 2016. Respondents were asked whether they currently or previously used e-cigarettes or combustible tobacco (including cigarettes, cigars or cigarillos), or both, as well as whether they had ever been diagnosed with COPD, chronic bronchitis, emphysema or asthma.

Glantz and Bhatta found that people who reported being current or former e-cigarette users at Wave 1 of the study had about a 30 percent higher risk of developing a respiratory disease at Waves 2 and 3, compared with people who had never used the devices. This danger was not as dire as that of current tobacco smokers at Wave 1, who had about a two-and-half-times higher chance of respiratory illness in later waves. But people who used both e-cigarettes and combustible tobacco had the greatest riskthey were 3.3 times as likely to develop a respiratory disease as someone who had never smoked or used e-cigarettes. The findings suggest e-cigarette use is a risk factor for respiratory disease independent of conventional smoking.

Robert Tarran, a professor of cell biology and physiology at the University of North Carolina at Chapel Hill, who was not involved with the paper, says the findings were not all that surprisingbut the fact that this was a longitudinal study strengthens what previous observational ones have found. It basically confirms what people in the field were thinking, which is that vaping isnt good for you, Tarran says. He and his colleagues published a study earlier this year that found that vapers had elevated levels of proteases (proteins that cut up other proteins) in their lungs. Such elevated levelssimilar to those seen in smokerscan lead to emphysema. And just as it can take a long time for the effects of smoking to cause serious disease, we're kind of concerned that with vapers, youre going to see a similar thing, where kids who start vaping now40 to 50 years from now, there's going to be a big epidemic of COPD and lung cancer, Tarran says.

Glantz says he was somewhat surprised that he and Bhatta could detect the increased disease risk in just two yearsthe length of time over which people were tracked in the PATH Study. They also calculated whether switching completely from conventional smoking to e-cigarettes lowered the risk of disease and found that it did. Almost none of the people who used e-cigarettes at Waves 2 and 3 of the study had stopped smoking combustible tobacco, however. Instead smoking both e-cigarettes and combustible tobaccoso-called dual usewas much more common.

Last week, a group of public health researchers published an opinion piece in Science arguing that policies seeking to restrict or ban vaping may be counterproductive, because many adult smokers rely on e-cigarettes to help them quit smoking. But the new findings could undermine this view. The concept that smokers would transition from using cigarettes to e-cigarettes and substantially reduce their health risks is not a crazy idea, says Glantz, who is also a nonsmokers rights activist. But if you look at actual use behaviors, they multiply. And since most people are dual users, youre getting increased harms. In addition, there is the fact that millions of young people who are not regular smokers are getting addicted to e-cigarettes, he adds. (Scientific American reached out to e-cigarette company JUUL Labs and the Vapor Technology Association, a vaping industry trade organization, for comment but did not receive a response.)

The mechanism of lung damage with chronic e-cigarette use is probably different from that behind EVALI, Glantz notes. About 80 percent of those hospitalized in the EVALI outbreak reported vaping THC, and the lung damage in those patients resembled that caused by chemical burns. The U.S. Centers for Disease Control and Prevention has identified vitamin E acetatea type of oil used as a thickening agent in some THC vaping productsas a possible chemical of concern, although the agency is exploring other possible mechanisms.

The PATH Study was focused mainly on tobacco use and did not distinguish between use of nicotine and marijuana e-cigarettes, Glantz says, adding, If had to do it over again, Id include marijuana in the model.

Regardless of whether vaping involves THC or nicotine, though, neither are probably good for the lungs, according to Glantz, adding, As my pulmonologist friends say, lungs are designed to inhale air.

*Editors Note (12/20/19):This article was updated to clarify that most of the products associated with the EVALI outbreak were black-market products.

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Vaping May Increase the Risk of Chronic Respiratory Disease - Scientific American

Anatomy

The anatomy of the MyKings botnet, and why it matters for security – CyberScoop

Written by Sean Lyngaas Dec 18, 2019 | CYBERSCOOP

Deconstructing a zombie army of comprised computers commonly known as a botnet can tell you a lot about the security weaknesses over a range of digital infrastructure. The unpatched machines the botnet preys on, the protocols it uses, and the malicious code it distributes come into sharp focus.

A new study of the MyKings botnet a notorious horde of computers that has netted crooks some $3 million by antivirus firm Sophos highlights how Windows servers are vulnerable to a range of attacks from the botnet.

The MyKings botnet, also known as Smominru, is like a mash-up of recent security trends: it has been used to mine cryptocurrency, it has taken advantage of users failure to patch their systems, and it has employed a software exploit released by the Shadow Brokers.

MyKings authors have also started experimenting with steganography an increasingly popular technique in which hackers hide their malware in a benign-looking image. In MyKings case, they disguised their code in a photo of musical artist Taylor Swift, and used it to update the botnet, according to Sophos.

Whoever is behind MyKings knows that retaining access to a network requires a subtlety not associated with botnets. And so they added a component to the botnet known as a bootkit that launches a malicious program whenever a computer is rebooted.

The MyKings botnet also has the regenerative powers of a cockroach.

Even if most of the components of the botnet are removed from the computer, the remaining ones have the capability to restore it to full strength simply by updating themselves, Sophos researchers Gabor Szappanos and AndrewBrandtwrote in a blog post Wednesday.

Since researchers began tracking it in 2017, the MyKings botnet has infected well over 43,000 unique, public-facing IP addresses, according to Sophos. If the internet is ever be to rid of the scourge, understanding how and why the botnet continues to be effective is key.

For the past couple of years, this botnet has been a persistent source of nuisance-grade opportunistic attacks against the under-patched, low-hanging fruit of the internet, Szappanos andBrandt wrote.

Its worth noting the amount of work that has gone into building this large botnet simply to run cryptominers, Brandt told CyberScoop. The cybercriminals approach is working and theyre making money, but the cryptominer is ultimately a quaint, anticlimactic result after significant build up and effort on their end.

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The anatomy of the MyKings botnet, and why it matters for security - CyberScoop

Anatomy

Carla Gugino & more to star in Anatomy of a Suicide at Atlantic Theater Company – New York Theatre Guide

Atlantic Theater Companyhas revealed initial casting for its previously announcedUS premiere ofAlice Birch'sAnatomy of a Suicide, directed byObie Award winnerLileana Blain-Cruz, which will now begin previews on February 1, 2020 (instead of January 30) at the Linda Gross Theater, ahead of an official opening on February 18 and a limited run through March 15, 2020.

The cast ofAnatomy of a SuicideincludesCeleste Arias (as Anna), Jason Babinsky (as Tim, Toby, Steve & Mark), Gabby Beans (as Bonnie), Ava Briglia (as Daisy, Anna & Child), Carla Gugino (as Carol), Julian Elijah Martinez (as Jamie), Jo Mei (as Jo, Laura & Lola), Vince Nappo (as Dan, Felix, Dave, Luke & Nick), and Miriam Silverman (as Emma, Karen, Daisy, Esther, May & Diane). Additional casting will be announced shortly.

Synopsis: "Three generations of women. Their lives play out simultaneously. For each, the chaos of what has come before brings a painful legacy.Anatomy of a Suicideis a revelatory exploration of mothers and daughters."

The creative team featuresscenic design by Mariana Sanchez, costume design by Kaye Voyce, lighting design by Jiyoun Chang, and projection design by Hannah Wasileski.

Currently playing at the Linda Gross Theater, Atlantic'sworld premiere ofHalfway Bitches Go Straight to Heaven, written byPulitzer Prize winner Stephen Adly Guirgis anddirected by Obie Award winner John Ortiz, continues its limited run through January 5, 2020.

(Phot courtesy of Boneau/Bryan-Brown)

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Carla Gugino & more to star in Anatomy of a Suicide at Atlantic Theater Company - New York Theatre Guide

Anatomy

The Anatomy of the Pitmaster Nap at Bark City BBQ – Eater Portland

The Pitmaster Nap at Eater Portlands 2018 Food Cart of the Year, Bark City BBQ, is basically a pile of meat. It has a sausage, ribs, pulled pork, and turkey, not to mention the various sides. What it doesnt have, unlike many of the barbecue platters in town, is brisket.

Its kind of like the IPA of barbecue, says Bark City pitmaster Michael Keskin. Keskin, who worked in Portland restaurants like Paragon and Podnahs Pit, now runs a barbecue cart in Southeast Portland food cart pod Hawthorne Asylum. Its been his dream to open a barbecue cart for years, but as Portland develops a stronger and stronger barbecue scene, Keskin had figured out how to distinguish himself: Letting the Texas barbecue others have mastered take a backseat, allowing himself to create his own versions of classics.

The Pitmaster Nap, then, ends up being a sampler tray of his greatest hits. Here, we break down the intricacies of Keskins sampler tray, from the sides to the sausages.

The ribs at Bark City are an amalgamation of various ribs Keskin has eaten in his barbecue-obsessed years, including the ribs at Rendezvous in Memphis. Ribs start with a dose of Carolina mustard vinegar sauce, before theyre rubbed with a combination of paprika, black pepper, dry mustard, and cumin, among other seasonings. The ribs smoke for about four hours, occasionally mopped with a combination of pickle juice, cider vinegar, water, and beer. The ribs come dry, but its smart to ask for one wet and one dry the wet ribs are tossed in barbecue sauce. All the Texas boys are about dry-dry-dry, Keskin says. I wanted to do something a little different.

The pulled pork at Bark City gets a similar treatment to the ribs same marinade, same rub before they hit the smoker. The pork shoulder goes in for about 10 hours, before it hits another fork in the road: If the pork comes pulled, it ends up tossed with Carolina vinegar and mustard barbecue sauces. If it comes chopped, on the other hand, it ends up chopped and tossed with Carolina vinegar and Bark BBQ sauce. Something noticeable in both the ribs and the pulled or chopped pork are the notes of vinegar in the sauces and marinades, similar to the various barbecue styles spotted in North and South Carolina.

When Keskin was in college, summer nights often involved beer links. We would drink and throw those Johnsonville beer brats on the grill, Keskin remembers. So he decided to recreate those college memories and make his own. Keskin combines pork and brisket trim for his sausages, as well as Caldera lager, dry mustard, cumin, salt, garlic, and crushed chile. The sausages cure for two days, which helps the smoke adhere to the sausages. When they finally make it to the smoker, they smoke for about an hour, giving them just enough snap and juiciness.

When Keskin started building his menu, he knew he wanted to have some sort of healthy option. The turkey, however, has become one of his best items, and perhaps the most distinctive. Keskin brines turkey breasts in salt and pepper for 24 to 48 hours, before they smoke for 1 12 to 2 hours over white oak. Then, the turkey sits in foil with butter for about 10 minutes. The turkey is remarkably simple, and particularly good with the barbecue carts Alabama white sauce.

The Pitmaster Nap comes with a choice of sides, ranging from barbecue beans to coleslaw, but the move at Bark City is to go with the restaurants pickled avocado and its potato salad. Keskin spotted the recipe for pickled avocados on Pinterest and loved the idea the fattiness of the avocado would mimic the fattiness of the meat, with a little acid for contrast. The potato salad, on the other hand, is a classic picnic potato salad: celery, pickles, egg, mayo, dijon, Yukon Golds, and celery salt. But every plate also comes with a Texas candied jalapenos, pickled barbecue onions, and a wedge of cornbread, baked in a cast-iron skillet each morning.

Bark City BBQ [Official] Previous Bark City coverage [EPDX]

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The Anatomy of the Pitmaster Nap at Bark City BBQ - Eater Portland

Anatomy

The anatomy of a Trump smear – CNN

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The anatomy of a Trump smear - CNN

Anatomy

Tunefind’s Top TV/Film Syncs of 2019: ‘Grey’s Anatomy’ On Top for Third Year, Billie Eilish Rules Artists List – Billboard

For the year in a row, no series had a bigger year when it came to TV music syncs than Grey's Anatomy.

Tunefind, a music discovery website that partners with The Hollywood Reporter and Billboard to present the Top TV Songs chart each month (ranking songs that appear in TV shows each month using a combination of metrics from Tunefind and Nielsen Music), has revealed its 2019 year-end data, sorting the top songs, shows, movies and more based on traffic and interaction on the Tunefind website.

After reigning in 2017 and 2018, ABC's Grey's Anatomy rules the top shows list yet again, maintaining its reputation as a tastemaker for music discovery on television. In 2019, the series premiered its 16th season. Expect to see the show gracing this list in 2020, as well, as the drama, whose music supervisor is Alexandra Patsavas, has already been renewed for season 17.

Programs supervised either solely or in part by Patsavas take the top two spots on the year-end top shows tally, as Lucifer, co-supervised by Patsavas with Justin Kamps, ranks at No. 2. That's a three-spot jump for Lucifer in 2019 and is two positions higher than its previous year-end best, No. 4, in 2017.

Suits, Peaky Blinders and The Blacklist round out the top five, while the top new show of 2019, Euphoria, ranks at No. 6.

While Grey's Anatomy is the year's top show overall, runner-up Lucifer contains the year's top song, "My Love Will Never Die," performed by AG and Claire Wyndham, from the season four finale, the show's first season on Netflix after FOX initially canceled the series in May 2018.

"My Love Will Never Die" is followed by a fully instrumental track: "The Night King," from the pivotal third episode of Game of Thrones' eighth and final season. The song was scored, like the show's entire run, by Ramin Djawadi.

Spider-Man: Into the Spider-Verse reigns as the top movie of 2019 with a budget of $25 million or more, a fitting rule given its soundtrack's No. 2 peak on the Billboard 200 dated Jan. 26 (and seven weeks in all within the chart's top 10). Its most prominent song, "Sunflower (Spider-Man: Into the Spider-Verse)," by Post Malone and Swae Lee, crowned the Billboard Hot 100 for a week in January.

After rules the list of top movies with a budget of less than $25 million, while Netflix's Someone Great wraps as the year's top streaming movie.

As for artists, Ruelle continues her hot streak, as she's never ranked outside the top two of the top artists of each year, ruling 2018's list and ranking at No. 2 in 2017. In 2019, she's No. 2 again, below Billie Eilish, who crowns the top artists of 2019 ranking. Eilish was everywhere in 2019, and television was no exception, with her music appearing in Dickinson, Hawaii Five-O, Veronica Mars, Riverdale and more.

The top composer of 2019 is Ezra Furman, who helmed the soundtrack to the 2019 Netflix film Sex Education, followed by Labrinth, who did the same for Euphoria.

Check out the full ranking for 2019 below, via Tunefind.

Top Songs1. "My Love Will Never Die," AG & Claire Wyndham,Lucifer2. "The Night King," Ramin Djawadi,Game of Thrones3. "When I R.I.P.," Labrinth,Euphoria4. "Phantom of the Opera Medley," Lindsey Stirling,The Umbrella Academy5. "Mannish Boy," Muddy Waters,Sex Education6. "Lost Without You," Freya Ridings,Grey's Anatomy7. "In Every Dream Home a Heartache," Roxy Music,Mindhunter8. "Got It in You (Acoustic)," Banners,The Good Doctor9. "The Woods," The White Buffalo,Marvel's The Punisher10. "Hard Times (feat. Congratulation)," Vision Vision,The Blacklist

Top TV Shows1. Grey's Anatomy (supervisor: Alexandra Patsavas)2. Lucifer (Alexandra Patsavas & Justin Kamps)3. Suits (Oliver Hild & Stacy Wallen-McCarthy)4. Peaky Blinders (Amelia Hartley, Pete Saville & Zoe Ellen Bryant)5. The Blacklist (John Bissell)6. Euphoria (Jen Malone)7. Riverdale (Alexandra Patsavas)8. The Umbrella Academy (Maggie Phillips)9. Sex Education (Matt Biffa)10. Power (Jennifer Ross)

Top New Shows1. Euphoria (Jen Malone)2. The Umbrella Academy (Maggie Phillips)3. Sex Education (Matt Biffa)4. Russian Doll (Brienne Rose)5. YOU (Season Kent & Alexandra Patsavas)

Top Movies (Budget Over $25 Million)1. Spider-Man: Into the Spider-Verse2. Joker3. Aquaman4. Creed II5. Avengers Endgame

Top Movies (Budget Under $25 Million)1. After2. Five Feet Apart3. Booksmart4. Green Book5. Good Boys

Top Streaming Movies1. Someone Great2. The Last Summer3. Tall Girl4. The Perfect Date5. The Kissing Booth

Top Artists1. Billie Eilish2. Ruelle3. Jessie Reyez4. Sleeping At Last5. Bishop Briggs6. Freya Ridings7. Michael Kiwanuka8. Imagine Dragons9. The White Buffalo10. Leonard Cohen & Queen (tie)

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Anatomy

Anatomy of a scene: Benny and Josh Safdie on creating chaos in ‘Uncut – Fast Company

Just how immersive is Uncut Gems, the cinematic Molotov cocktail from adrenaline junkies Benny and Josh Safdie? At one point, viewers get a glimpse of our protagonist, diamond district hustler Howard Ratner (Adam Sandler), from inside his colonoscopy.

Its the visual pun of meeting an asshole through his asshole, Josh Safdie said recently, in an interview with Fast Company.

Ratner is a risk-prone entrepreneurial hurricane, constitutionally incapable of not trying to make a dollar out of 15 cents. (And $15K out of that first dollar.) Although Uncut Gems only puts viewers physically inside of Ratner for a brief moment, the remainder of the film plunges us into the constantly shifting juggle session of his existence, daring us to look away. Someone is always calling to buy something from Ratner or sell something to him; someone else is stopping by unannounced in his Manhattan showroomor his childs school playto collect on an outsize debt. There are bookies and brokers, soon-to-be ex-wives and girlfriends, authentically scuzzy bagmen, and former NBA all-star Kevin Garnett, for good measure. Its hard to keep it all straight, just as a viewer, so one can only imagine the toll it takes on Ratner himself.

The plot of Uncut Gems is almost incidental: Ratner is trying to negotiate his biggest-ever score but keeps getting in his own way. Through masterful technique and thrilling performances, the film transcends its plot to become an overwhelming, full-sensory experience.

One scene in particular, though, boils down the manic energy of the film into one easily digestible dose. Its the scene in which Kevin Garnett (playing himself), his bodyguard (Sean Ringgold), and fellow hustler Demany (Lakeith Stanfield) pay a visit to Ratners showroom and get stuck in the vestibule. Ratner and his staff are doing their best to get them out, with Ratner already discombobulated from morning phone calls after a night spent sleeping in his office. (Throughout the scene, a tag is visibly hanging out of the shirt hes just thrown on.

Not a lot seems to happen, but on screen, its a capsule summary of Uncut Gems nonstop movement, jarring noise, and potent volatility. Below, Benny and Josh Safdie discuss the making of this scene.

If this scene leaves anyone in the audience reaching for a stress ball, rest assured: Its intentional. But its in the service of delivering necessary information in the most absorbing way possible.

Josh Safdie: How do you keep a thriller thrilling in a scene that has nothing to do with life or death? By raising the stakes. Increasing the tension.

Benny Safdie: This scene is all exposition, so the more tense and stressful it is, the better.

JS: In a weird way, the required energy and the required madness that surrounded the character was very helpful to us. It feels so naked when youre just doing exposition, so you want to figure out the way exposition exists in real life because there is exposition in real life all the time. Someone will say, You have to be here in 15 minutes.

BS: Or else!

JS: Thats exposition that happens in life. And its not strange when it happens in life. So we tried to figure out ways to kind of sidle up alongside that feeling. And sometimes, the madness really helped allow us to kind of not cover the tracks of exposition, but in a weird way, support it.

The claustrophobic feeling of the scene is a result of the fact that its all one big interconnected set.

JS: Being true to life of the guys in the diamond district, its such an overstimulated world. First you have this overstimulation [that] each space is over-designed. Theyre filled with insane precious jewels and intricate jewelry and you have deal over deal over deal and gamble on top of gamble on top of gamble.

BS: We wanted to capture the energy of 47th Street [New York Citys diamond district], so we had this space and we built it with the hallway, the showroom, and the back roomall connected for the purposes of realism. You really did feel like you went into it when you walked in. You got out of the elevator, went down a hallway with all these stores, and then entered Howards store. And then right on into the back. It wouldve been much easier to just do each one separate, to get all the camera angles and whatnot, but we built it like it was a real location. So then were like, Oh, lets just shoot it like a real location. We shouldnt keep ourselves so separate from each space. So we really did go in the back and out the front and everywhere else each time.

Further propelling the immersive feeling of the scene is filming it as a single, flowing shot, following around whoever becomes the focus of the scene for that moment.

BS: The day before that shooting, we had our shot list all prepared, and it was something like 45 shots to get in one half-day. It was physically impossible. And were thinking about how do we show this in a way that would be interesting but also catch all of the craziness thats happening. And it was like,Okay, if we can somehow do this in one shot, that would be incredible. And so that was our attempt at doing the sweeping camera motion of it. The whole thing was done in one take. Then we got all the inserts that kind of magnify every moment, and the reverse shot of Sandler.

JS: What it did for the actors is it allowed them to feel the whirling dervish quality of the scene, that theres so much going on. And I think that that added an element of dance to the whole thing because everyone had to be in sync for the camera movements. I remember LaKeith [Stanfield] was like, That shots probably really crazy.

BS: The idea behind it was to capture this feeling directly with like the handoff of responsibility. So youre literally just panning with all of the baton passes to try and get these people out. Youre feeling the emotions and the speed that all these people are going through, trying to get them out. Then on top of that, we had somebody in the showroom also who isnt a part of the scene, just a guy who is hanging out in the showroom, and we went back in later and ADRd a whole scene that hes having, narrating whats going on in addition to the conversations that are going on in the scene. And we were worried, like, Is this too much?

JS: When we first started showing the edited version of that scene, I remember people just being like, Whoa, thats the craziest thing Ive ever seen in my life.

The scene is also a cacophonous dirge of abrasive noisesa buzzer pressed over and over again, a ding-dong ring, a fist pounding on glass, and random mechanical whirring. Putting it all together was apparently like conducting a neurotic orchestra.

BS: When you get to the sound mix, you realize you can actually affect the sound both behind the glass and in front of the glass, and that became another added level of stress, where its kind of hard to hear the other person cause theyre behind glass.

JS: I think the musicality of it all also helped add to the banging, the percussive elements, Roman [Roman Persits] going into the back room . . .

BS: Its literally trying to match your version of reality, which is like a hyperreality, to real life. The buzzer is so loud, and its the perfect buzzer. But we went back and watched a bunch of the showroom scenes and it wasnt feeling real. It didnt feel like what it was supposed to feel like. So we went back to the district and recorded a bunch of Foley and as were in the showroom we hear, Oh there are other people talking. You hear that their cell phone rings are going off. So we added cell phones, and then we went into a bunch of jewelers to get their different buzzers. But when we walked in one where I was just recording sound, and then Josh was listening to the tapes back with the sound designer and hes like, Whats that noise? And it was this high-pitched ahhhhhnnn. Hes like, What is that? And youre like, Oh wait, when we open the front door of this guys space, that noise went off until it was closed. So we put that in every showroom scene. Whenever that front door opens, you hear a very high-pitched noise and that adds a level of stress and this feeling of realness. In my mind, it broke the reality of that whole space. Like, its 100% real.

Part of what stresses out the audience in this scene is watching the performers lose patience in a relatable way. It doesnt happen all at once. Demany is completely over the situation within 20 seconds, the bodyguard takes a little longer, and then Kevin Garnett finally loses his cool a bit too. Its all carefully calculated to elevate your heart rate.

BS: The scene builds in a way, as youre moving through it. Theres a level of frustration that naturally builds and so it had to build to a certain level for Lakeith to get to the energy of him entering that back room when he gets out. Oh, and then theres the bodyguard.

JS: He has my favorite line in the scene. I talked to that actor, Sean, and I said to him, You hate small spaces. And he goes, What? I said, Youre claustrophobic. He goes, Oh shit. Hes in there with Kevin Garnett, this really big guy, and its a small space. More stress. It wasnt in the script for him to say Im claustrophobic. But then he picked the most perfect time to say it, when he realizes hes trapped. And then he does that thing with the door to try to get out, and we actually built the stage so that those doors were locked for real. So hes yanking on that back door, and it doesnt open. Kevin Garnett is actually the most relaxed until when he gets out and he just lets out that sigh. I love that.

Excerpt from:
Anatomy of a scene: Benny and Josh Safdie on creating chaos in 'Uncut - Fast Company