Daily Archives: January 9, 2022

Our gut microbiome helps us out every day by processing the fiber we cant digest. The bacteria ferment the fiber into key chemicals known as short-chain fatty acids, or SCFAs, that are essential for human health. SCFAs fight inflammation, help kill dangerous bacteria, protect the lining of the gut, and can even help prevent cancer.

In a new study, the John Denu lab at the University of WisconsinMadisons Wisconsin Institute for Discovery has learned that the fatty acids butyrate and propionate also activate p300, a crucial human enzyme that promotes the unspooling of DNA. This unwound DNA allows more genes to become active and expressed, which ultimately affects human health.

Previous research had suggested that SCFAs might instead contribute to this process by inhibiting a different set of enzymes.

John Denu

Sydney Thomas

This new understanding opens the possibility of activating p300 in a diet-dependent way or even independently of the microbiome. Knowing how to target p300 is vital because it is implicated in a wide variety of physiological processes and diseases, such as propionic acidemia, autism spectrum disorder, and Alzheimers disease.

Knowing that butyrate and propionate directly interact with this protein opens up a lot of new areas of research that we didnt even think to look at before, because we thought that it was happening the opposite way than it actually is, says Sydney Thomas, a Denu lab graduate student and co-author on the paper.

Thomas and Denu, a professor of biomolecular chemistry, published their findings Oct. 22 in the journal eLife.

Earlier work in mice had shown that SCFAs are a crucial link between the microbiome and epigenetic states the modifications to DNA that affect how active any given gene is. These epigenetic modifications allow different cells to use the same DNA instructions to perform different tasks and can affect health.

One key mechanism of control that cells use is to organize the DNA so only certain parts of it can be accessed for the work at hand. To do this, cells wrap DNA around histone proteins, which act like spools for the DNA thread. Modifying histones changes the accessibility of the DNA wrapped around them, and ultimately changes which part of DNA a cell uses.

Science is most thrilling when you discover something unexpected and when the results challenge long-held beliefs. This work checks both those boxes.

John Denu

The mouse model work had left it unclear precisely how cells sense SCFAs and react by altering their histones to control gene expression. To address these outstanding questions, Thomas and Denu treated several human cell lines directly with SCFAs, bypassing the more complex mouse experiments.

Adding propionate or butyrate to the cells led to rapid changes in the cells histones. When they looked at how the compounds accomplished these changes, the team discovered that the fatty acids released the brakes on p300, which went on to modify histones in a way that opened up DNA to be used by the cell.

These findings largely replicated the results from the prior mouse work, indicating that the cells were an effective and simpler system to test how SCFAs alter the epigenome of the host.

We are hoping that now that we have a better understanding of how SCFAs work (and) can use this knowledge to create better drugs and a deeper understanding of how the microbiome interacts with the host, says Thomas.

For decades, textbook dogma held that butyrate and propionate altered chromatin by inhibiting the enzyme histone deacetylase. But the new findings that the fatty acids instead work by activating p300 call this old model into question.

Science is most thrilling when you discover something unexpected and when the results challenge long-held beliefs. This work checks both those boxes, adds Denu.

The research was funded by the National Institutes of Health.

See the article here:
New way to alter DNA, affect health circumvents gut bacteria - University of Wisconsin-Madison

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Original post:
Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs - Nature.com

HASTINGS, Mich. (WOOD) Ashley Copelin was 2 months old when her mom left the family home in Barryton, a small village east of Big Rapids, for a gallon of milk. They were living with grandpa and grandma.

That was on May 17, 1987.

Nobody has seen her mom, Margie Ann Ranshaw, in the nearly 35 years since.

I just want people to know her name, Copelin said on Friday.

She said recent breakthroughs in missing persons cases in Kent and Ottawa counties are giving her renewed hope for her moms case which quickly went cold.

I dont believe that shes alive, she said. But I do believe that her body is out there somewhere, and I do believe that we deserve to know what happened to her, regardless if shes dead or not.

Her mom was 29 when she vanished. Shed be turning 64 this month.

In NAMUS, the National Missing and Unidentified Persons System, shes listed as Missing Person Case No. 14788.

She was sick. She had schizophrenia, Copelin said of her mom. She told my grandfather right before she left that the voices were telling her to leave, and my grandfather was telling her she had to fight through that and she had to ignore those voices.

Her mom, she said, had dreams of living out west.

She would often hitchhike and she would be gone for months at a time. She would always come back, Copelin said.

This time, police found her car abandoned two weeks later two hours away at a hotel in Howell. Most of her family believes she was the victim of foul play.

The investigation by the Mecosta County Sheriffs Department never turned up any answers.

An aunt and uncle adopted and raised the missing moms daughter.

I had a great life, and I had a great childhood, Copelin said.

She now is raising two kids of her own in Hastings.

There was a hole missing in my heart, and I had pain that stuck with me my whole entire life, she said.

She has tried finding her mom on her own background searches, Google searches with an outside hope that shes still alive.

No matter what kind of research I do, no matter what I do, it comes to a dead-end with her, she said. And I believe, I have come to the conclusion that its something that maybe God doesnt want to reveal.

She reached out to Target 8 after learning that genealogy researchers working with DNA had identified two bodies found decades ago in West Michigan: remains previously known as Ada Bones in Kent County and Matilda in Ottawa County.

It gives me a lot of hope, she said. Some families are getting their justice 40, 45 years later, and Im hoping for that chance ourselves.

Her mom is among 619 people listed by NAMUS as missing from Michigan. Anyone with information on this case is asked to call the Mecosta County Sheriffs Department at 231.592.0150.

See the rest here:
DNA breakthroughs give new hope to daughter of missing mom - WOODTV.com

Massimo Giachetti/iStock Editorial via Getty Images

Codex DNA (DNAY) is a $267m market cap biotech that IPOd in June last year, raising $123m at $16 per share. The company was spun out of Synthetic Genomics (since renamed Viridos) in 2019, having been founded under the name SGI-DNA in 2013 - co-founder Thomas Gibson developed the Gibson assembly method of cloning DNA, and currently serves as Chief Technology Officer.

The company described itself as follows in its IPO prospectus:

We believe that we are a leading synthetic biology company focused on enabling researchers to rapidly, accurately and reproducibly build or write high-quality synthetic DNA and mRNA that is ready to use in many downstream synthetic biology enabled markets.

A key part of our solution is our BioXp system, an end-to-end automated workstation that fits on the benchtop and is broadly accessible due to its ease-of-use and hands-free automation.

We believe our BioXp system can democratize synthetic biology by simplifying the process of building DNA and mRNA, thereby accelerating the discovery, development and production of novel high-value products, including antibody-based biologics, mRNA-based vaccines and therapeutics and precision medicines.

The list of companies that either have been or are currently using Codex' instruments and consumables includes reputed academic institutions such as Duke University, the Memorial Sloan Kettering Cancer Center, and MiT, large pharmas including Johnson & Johnson (JNJ), Eli Lilly (LLY) and Merck (MRK), gene therapy specialist Editas (EDIT) and even BioNTech, co-developer of the $36bn selling (in 2021) Comirnaty COVID vaccine, alongside Pfizer (PFE).

Codex says it has ~160 installed bases of BioXp, and reported earnings of $2.2m in Q321 - up 69% year-on-year, and up from $2.12m in Q221. Year-to-date earnings in Q321 were reported as $8m - up from $6.6m across the whole of 2020, and $4.8m in 2019 (according to a recent investor presentation).

These are not sales figures to make investors tingle with anticipation, and so it has proven - Codex' share price since its IPO has been on a downtrend, falling from a high of $22 in June last year, to a low of $6.2 by late December.

Things may be about to change for Codex and its valuation, however, thanks to a partnership agreed with Pfizer, who will make an initial upfront payment of $8m for the right to firstly collaborate on improving, and then to use Codex' platforms and instruments to "produce certain materials of interest to Pfizer."

According to an 8k filing by Codex, there's a further $10m on the table in the near term if Codex meets "certain technical milestones," and if Pfizer successfully develops products using the technology, up to $60m in clinical development milestone payments, and $180m in sales milestones per exclusive product.

When announced in late December, the news of the deal sparked a brief rally in Codex stock, to $11 per share, which has since fallen to $9.25 per share. It may not seem like much, but the long-term implications of the deal could be hugely significant.

Pfizer shares rose in value by ~50% last year, and of all the major pharmaceuticals, looks to have the most momentum going into the new year. This is primarily down to its co-development of Comirnaty alongside BioNTech, the Germany based biotech that is considered, alongside Moderna (MRNA) to be the world's premier developer of messenger-RNA technologies.

Even so, without BioNTech at its side, Pfizer showed it can develop specialist drugs of its own in 2021 with the development of Paxlovid - an oral antiviral that reduced the risk of COVID-19-associated hospitalization or death by 89% in those who received treatment within three days of symptom onset.

Pfizer's CEO Albert Bourla has occasionally made noise about pursuing mRNA technologies without BioNTech as a partner, and as small as the Codex deal is for a pharma of Pfizer's size - its current market cap stands at $312bn - it seems to be a clear indication that the company has ambitions in this space.

We may not see much in the way of value adding developments on Pfizer's part in 2022 - neither Moderna nor BioNTech have made much tangible progress with mRNA outside of the COVID vaccine space yet, although both have assets targeting types of solid tumor cancer, as well as vaccines focused on viruses including Respiratory Syncytial Virus ("RSV"), influenza, and others - but Pfizer's decision to partner with Codex could have a very positive influence on the biotech's reputation and share price this year.

Codex' platform spans both synthetic DNA and mRNA manufacturing at industry leading speed. Source: Codex investor presentation December 2021.

According to Codex' IPO prospectus, in 2020 the company's work was divided as follows:

Areas of focus: 45% biologics, 27% vaccine development, 14% cell and gene therapy, 12% genome editing and 2% agriculture.

Research area: 37% immuno-oncology, 35% infectious disease, 18% genetic/rare disease and 10% other.

Application: 23% vaccines, 21% protein engineering, 20% cell engineering, 20% antibody engineering and 16% nucleic acid engineering.

Customer type: 43% biotechnology development, 23% academic institutions, 14% pharmaceutical development, 12% other and 8% contract research.

As we can see in the slide above, Codex' systems are able to write both synthetic DNA and mRNA, and it's the latter that's likely to most interest Pfizer initially. The process of writing either is highly complex and involves multiple steps carried out by highly skilled professionals, as shown below:

Breaking down the steps required to build DNA and mRNA. Source: Codex investor presentation December 2021.

Codex' unique selling proposition is its ability to automate multiple elements of the process, thereby saving time and money, by creating a push-button, end-to-end solution that can build functional grade synthetic DNA and mRNA.

Presumably, Pfizer would wish to initially use CODEX and its BioXP system to write the SARS-Cov-2 spike protein gene that is delivered using mRNA, wrapped in a protective lipid nanoparticle ("LNP"), inside patient's cells, allowing their immune systems to create antibodies to prevent the virus gaining entry into the cell and reproducing.

It's not immediately obvious what size of contribution Codex could make to this process - Pfizer expects to manufacture ~2bn Comirnaty vaccines in 2022, which is likely to be far in advance of the biotech's capabilities, and the pharma will almost certainly have medium-term agreements in place with other manufacturers ensuring it is able to meet demand.

But if Pfizer is turning its attention to developing other types of mRNA vaccines, perhaps Codex could become its preferred development partner. It's a deal that may suit both parties, given that Pfizer will value the privacy provided by the partnership, opportunity to shape Codex' product development, and the cost saving that partnering with a smaller company will likely bring about.

Codex itself would benefit from becoming a preferred supplier of technology to Pfizer, selling large volumes of its products, and in all likelihood the biotech would become an attractive acquisition target for Pfizer, who won't want to share trade secrets with Codex' other clients - it would be wiser to bring the entire operation in-house, and Pfizer more than has the resources to do that.

Slide from Codex highlights speed and performance advantages of BioXP. Source: Codex investor presentation December 2021

When it comes to the writing / manufacturing of DNA and mRNA, speed and precision are clearly of pivotal importance, and according to Codex at least, the company has developed a competitive advantage, as we can see in the slide above.

Of course, every company will claim its own products provide a superior solution to its rivals, and it looks as though Codex does not have all bases covered yet - although the fact that Pfizer has committed itself to help develop Codex' systems ought to help the company broaden its product offering in double quick time.

Codex additionally claims that its IP portfolio is "amongst the industrys broadest and deepest synthetic biology IP portfolio," and that's another attractive selling point for Pfizer - witness the struggles Moderna has experienced contesting IP with the National Institutes of Health ("NIH") over its vaccine design and development, and with Arbutus Biopharma (ABUS) over lipid nanoparticles.

IP is tremendously important in the world of drug development, and it could be that Pfizer believes its deal with Codex will allow it to strike out alone as a developer of RNA or mRNA drugs with a partner far less mightier than e.g. BioNTech, who would gladly sacrifice some of its IP rights in exchange for a long-term partnership. It probably helps that Codex' co-founder created an entire gene assembly process, which is now named after him!

Turning to the market potential of Codex' platform and products, long term, the company views itself as capable of the "distributed manufacturing of DNA, mRNA and protein-based products," and one use-case highlighted by the company will certainly set investors pulses racing.

Codex outlines a potential response to a future pandemic. Source: Codex investor presentation December 2021.

If Pfizer is looking to future proof a rapid response to any pandemic that may emerge in the coming years, or even decades, a specialized platform that automates as many stages of mRNA vaccine design, manufacture, and distribution would be an excellent place to start, and that seems to be at least one of the company's ambitions with Codex.

Away from the pandemic, DNA, RNA and mRNA look set to play an increasingly pivotal role in the future of medicine and drug design, whether it be in the oncological, cardiovascular, autoimmune, genetic disease, or rare disease setting. Custom designing instructions to produce the right proteins in the right areas of the body is the central thesis behind the work of Moderna, BioNTech, and others more experienced mRNA drug developers, and it is an area that, until recently, was largely overlooked by larger pharmas.

Pfizer was the only pharma to develop mRNA technology in response to the pandemic, and it literally transformed the company's fortunes. In 2021, the company is likely to more than double its revenues, from ~$42bn, to ~$85bn - after seeing revenues shrink by >$10bn across the previous decade.

The big pharma had looked directionless at times over the past few years prior to the pandemic, but by stealing a march in the mRNA field it could truly become the dominant healthcare company for the next decade. The Codex deal at least hints at a company trying to cover all of its bases as quickly as possible, before its rivals catch up.

Codex is a relative minnow with a market cap scarcely above a quarter of a billion dollars, and although I have painted a rosy picture of what life could be like for the company as Pfizer's preferred partner, the reality is that big pharma's regularly make deals like this with small but promising biotechs, and as often as not, they come to nothing.

Beyond an initial $8m outlay, there's no guarantee that Pfizer will make any further investment into Codex or its technology. Arguably, Codex' technology is yet to be tested in a real world or an industrial setting, and the demands that a company such as Pfizer could place on it e.g. manufacturing the mRNA that goes into its Comirnaty vaccine - could push the company and its tech beyond breaking point.

Of course, BioNTech is a recent example of a company that flourished in partnership with Pfizer. It was a far larger company, that may not have had commercial products, but through its technology owned the key to unlocking the COVID vaccine conundrum. There are some parallels between BioNTech and Codex that may provide encouragement to an optimistic investor.

Pfizer's work with Codex does not necessarily guarantee any extra income for the biotech, and should the pharma elect not to take any products into development, Codex may continue to look like a promising company with cutting edge tech - but a dearth of paying clients. This appears to have been the chief underlying reason why the company's share price has fallen by >50% across the past 12 months.

Even a company with great technology is only as good as the companies that use that technology, and there is no shortage of competition in the DNA / mRNA writing space either.

Twist Biosciences is a good example of a company that does most of the things that Codex does, as well as many things that Codex doesn't yet do, such as DNA storage. Twist's share price has fared no better than Codex' however, down 48% across the past 12 months. Meanwhile, giants like Thermo Fisher (TMO) threaten to overwhelm the smaller competition with superior resources and a wider client base.

Codex could be one of the missing pieces that Pfizer needed to pick up on its path toward developing an mRNA therapeutics pipeline, with an initial focus on its COVID vaccine, protecting against future pandemics, and a wider focus on a range of different therapeutic modalities mentioned above.

Pfizer may have unearthed a perfect partner - a minor biotech with precisely the technology, IP protection and experienced management and staff the company needs - and Codex and its ~100 staff will likely be highly motivated to persuade the Pharma that it has all of these strengths in abundance.

That's an encouraging starting point for a deal that has largely flown under the radar, given the tiny sums involved. But the repercussions of the deal could one day be seismic for both companies.

That day is still a long, long way off, and as mentioned, pharma's experiment with the products of minor biotechs all of the time. The risk is largely on Codex' side, but it's also an opportunity to operate inside the eye of the COVID storm, prove its mettle, and make a name for itself - all of which would be transformational for its valuation.

If Pfizer believes that Codex has what it takes, it would make sense to acquire the company sooner rather than later - all of which adds up to an exciting 12 months for both companies, and a deal that, however small, should not be dismissed, and may be worth keeping a close eye on.

The rest is here:
Pfizer's Codex DNA Deal Hints At Lucrative Pivot To mRNA - Keep An Eye On This Space - Seeking Alpha

Sequence, Risk and Catan are only a few of the popular titles that can be found lining the walls of DNA Board Game Cafe in Khalidiya.

Located in Abu Dhabi's Montazah Tower, the cafe's interiors offer a striking contrast of navy blue and red with big round windows that let natural light flood in. Elsewhere, theres greenery on the walls as well as plants in the corner, adding an earthiness.

The cafe is the brainchild of Delilah Celik and Abdulaziz Alyassi, both of whom have a shared passion for playing board games. The decor is also a reflection of the couple, they tell The National.

Celik says shes a big Lord of the Rings fan, which explains the window stylings, while red is her favourite colour and navy blue is Alyassi's. Celik also loves retro vintage, a theme that can be seen throughout.

Retro vintage themes, navy blues and plush reds create the interiors of DNA Board Game Cafe in Abu Dhabi. Antonie Robertson / The National

The reason we went with a board game cafe theme is because we just love board games. Its so much fun. And we're both very competitive, says Celik. So, we were playing board games probably seven, eight years ago and then we just wanted to open our own cafe.

DNA comes from their first names, as, when they would play games together, their friends would chant D and A.

It's just a beautiful place to come with family. There's just a cosiness

Delilah Celik, co-founder

Currently, the outlet has more than 200 games that range from family-friendly to multiplayer. Some of them are strategic, while others offer more opportunity for social interaction.

Theres also a limited food menu on offer that features breakfast items such as French toast and pancakes, as well as sourdough toast options. Mains include a truffle burger on a black brioche bun and grilled tiger prawns or salad for those who want to eat lighter.

There are also cakes and desserts, as baking is another hobby that Celik enjoys. While theres plenty of space dedicated to the games, theres also a whole separate area for the baked goods. Partitioned from the rest of the cafe by a glass pane wall, the room is painted light pink with intricately decorated cakes on one side.

DNA Board Game Cafe also has a baked goods area. Antonie Robertson / The National

I love baking. I used to bake but I just don't have time now. So other people bake [for us]. But we call the space the cake basement and, originally, I did want it to be in a basement but I didnt get approvals, says Celik.

So far since opening in December, she says the cafe has had a warm reception. However, there has been some feedback on aspects such as parking, which can be limited in the busy area, as well as pricing.

Limited parking is available in the basement of the building, which people dont always realise, and Celik explains the price point: Its Dh19 per person for one hour, then Dh29 the second hour and then Dh39 for all-day rates, she says. If you're having food and drinks, that's off the menu but we wouldn't charge you while you're eating and drinking. Board games would usually go after or before.

"We usually don't mix up the games with the food because of Covid and the games would get spoiled. You can eat before but there's no table fees and it's just what you're eating from the menu.

Even though the space is new, there are already plans to expand to Ras Al Khaimah, where Alyassi is from. Celik also hopes to make more use of the "cake basement" by soon hosting cake decorating classes.

Overall, Celik says she really wants people to feel comfortable in the space, and is trying to build a sense of familiarity.

"It's just a beautiful place to come with family. There's just a cosiness," she says. "What I miss back home is there are little cafes that you'd find and everybody knows you by name. Like we're quite friendly out here."

Updated: January 8th 2022, 8:37 AM

Read more from the original source:
DNA: Abu Dhabi's new board game cafe with more than 200 options to play - The National

A WOMAN whose mom was killed and decapitated by the Time Square Killer believes there's a possibility he is her father and wants a DNA test to find out the truth.

Jennifer Weiss, 43, has been working with authorities in Bergen County, New Jersey, for years to help identify further victims of Richard Cottingham, who claims to have killed between 80 and 100 people in an 18-year spree.

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Weiss' own mother was among the most infamous of Cottingham's kills, earning him the nickname The Torso Killer after he tortured and beheaded her and an unidentified 16-year-old girl in a Times Square hotel.

The body of Deedeh Goodarzi was found in a burning room on December 2, 1979, with a firefighter making the gruesome discovery that the remains were lacking heads when he attempted to give mouth to mouth.

The skull of the Iranian immigrant, who had been working as a high-end escort in Times Square, was never found.

"It's possible but not probable because of the field of work she was in," Weiss exclusively told The Sun of Cottingham being her father.

"But because it's possible, it's unsettling.

"Although we haven't done a paternity test in the court of law, my whole feeling on it is still the same because it's possible."

Weiss was given up for adoption by Goodarzi when she was less than two weeks old and there was no information given on her biological father.

Adopted by a New Jersey family, she found out the truth about her mom's death when she was 24.

First writing letters to now 75-year-old Cottingham in prison, she began to visit him in 2017 and has since met with her mom's killer more than 30 times.

She says that she does so to help bring out the truth about his other crimes and find justice for her mother and other victims.

When questioning Cottingham about the murders, he reportedly told Weiss that he had known Goodarzi for two years before he killed her, leading to her questions about whether or not he could be her father.

"If I was to pursue it in the court of law, I'd have to take him to court and do it legally," Weiss explained.

She said that she has hoped Bergan County authorities will help her in organizing the test after she has worked with the prosecutor's office in getting further information from Cottingham about his victims.

While he has said that he killed dozens of women, when Cottingham was eventually caught in the early 1980s, he was only charged and convicted with the death of five known victims.

Over the last four decades, he has admitted to a further six murders, pleading guilty to the killing of two teenagers in the 1970s as recently as April 2021.

Weiss said that she hopes a DNA test would not only prove once and for all whether or not Cottingham is her father but that it could be used to see if he has any other children apart from the three he had with his wife.

"We put his sample on the system we could see if I could be related or see if there's other children that could be related. And you know, that's just a whole other revelation," she said.

While Weiss would like to put the mystery to bed, she told The Sun that she is more interested in working to identify more victims and give families justice decades down the line.

"It would settle things for me, but it's not on top of my list," she said.

"It was never on my list until he said he'd been hanging around with Deedeh for a couple of years.

"It's a priority, but pretty low on the list. Nothing in my life will change.

"I'm still a great person and finding out that detail wouldn't change who I am."

Weiss told The Sun that she already knows of other victims of Cottingham's but that the slow pace of the official process means they have not yet been made public.

"I believe that there are other victims that were decapitated," Weiss claimed.

'You just haven't heard about them yet because we haven't had the chance to bring them to life, but they're in the lineup, for sure.

"It's an unusual thing to do to someone," she continued.

"But I think he was. He had done it many times before.

"It's just the public doesn't know that yet. I know it. But the public doesn't.

"And that's what I want. I want everyone to know the other women he killed and what he did to them.

"I have had contact with victims, family members," Weiss added.

"And that's a really good feeling.

"It doesn't come too often because these cases are so old, and most of the families are dead.

"But it's the children of the victims that have reached out and said that they were grateful for what I was doing.

"If we can work together, we could get it done quicker."

Cottingham managed to avoid detection until 1980 more than a decade after his first known murder - the killing of 29-year-old mother-of-two Nancy Vogel who was found naked and strangled in her car.

He only admitted to this killing in 2010.

Scouting for victims around Times Square, Cottingham worked a 3pm to 11pm shift in a health insurance company inManhattanwhile living with his wife and three children inNew Jersey.

He didn't leave any evidence at crimes scenes to connect the murders, leaving authorities unaware they were dealing with a serial killer.

The murderer was eventually arrested in 1980 after his wife filed for divorce and his killing spree appeared to ramp up

Cottingham was caught in the act in a hotel in New Jersey in May 1980 after the tortured screams of one of his victims alerted staff.

He had killed a woman in the very same hotel just over two weeks before.

Cottingham is serving a life sentence with no hope of parole in the New Jersey State prison.

It is believed the actual death toll of his murderous rampage will never be fully known or verified.

His story is explored in the Netflix documentary "Crime Scene: The Times Square Torso Killer" released last week.

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I think the Times Square Killer who dismembered my mom is my FATHER and I want a DNA test... - The US Sun

More and more people around the world are suffering because their immune systems can no longer tell the difference between healthy cells and invading micro-organisms. Disease defences that once protected them are instead attacking their tissue and organs.

Major international research efforts are being made to fight this trend including an initiative at Londons Francis Crick Institute, where two world experts, James Lee and Carola Vinuesa, have set up separate research groups to help pinpoint the precise causes of autoimmune disease, as these conditions are known.

Numbers of autoimmune cases began to increase about 40 years ago in the west, Lee told the Observer. However, we are now seeing some emerge in countries that never had such diseases before.

For example, the biggest recent increase in inflammatory bowel disease cases has been in the Middle East and east Asia. Before that they had hardly seen the disease.

Autoimmune diseases range from type 1 diabetes to rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. In each case, the immune system gets its wires crossed and turns on healthy tissue instead of infectious agents.

In the UK alone, at least 4 million people have developed such conditions, with some individuals suffering more than one. Internationally, it is now estimated that cases of autoimmune diseases are rising by between 3% and 9% a year. Most scientists believe environmental factors play a key role in this rise.

Human genetics hasnt altered over the past few decades, said Lee, who was previously based at Cambridge University. So something must be changing in the outside world in a way that is increasing our predisposition to autoimmune disease.

This idea was backed by Vinuesa, who was previously based at the Australian National University. She pointed to changes in diet that were occurring as more and more countries adopted western-style diets and people bought more fast food.

Fast-food diets lack certain important ingredients, such as fibre, and evidence suggests this alteration affects a persons microbiome the collection of micro-organisms that we have in our gut and which play a key role in controlling various bodily functions, Vinuesa said.

These changes in our microbiomes are then triggering autoimmune diseases, of which more than 100 types have now been discovered.

Both scientists stressed that individual susceptibilities were involved in contracting such illnesses, ailments that also include celiac disease as well as lupus, which triggers inflammation and swelling and can cause damage to various organs, including the heart.

If you dont have a certain genetic susceptibility, you wont necessarily get an autoimmune disease, no matter how many Big Macs you eat, said Vinuesa. There is not a lot we can do to halt the global spread of fast-food franchises. So instead, we are trying to understand the fundamental genetic mechanisms that underpin autoimmune diseases and make some people susceptible but others not. We want to tackle the issue at that level.

This task is possible thanks to the development of techniques that now allow scientists to pinpoint tiny DNA differences among large numbers of individuals. In this way, it is possible to identify common genetic patterns among those suffering from an autoimmune disease.

Until very recently, we just didnt have the tools to do that, but now we have this incredible power to sequence DNA on a large scale and that has changed everything, said Lee. When I started doing research, we knew about half a dozen DNA variants that were involved in triggering inflammatory bowel disease. Now we know of more than 250.

Such work lies at the core of Lee and Vinuesas efforts, which aim to find out how these different genetic pathways operate and unravel the many different types of disease doctors are now looking at. If you look at some autoimmune diseases for example, lupus it has become clear recently there are many different versions of them, that may be caused by different genetic pathways, said Vinuesa. And that has a consequence when you are trying to find the right treatment.

We have lots of potentially useful new therapies that are being developed all the time, but we dont know which patients to give them to, because we now realise we dont know exactly which version of the disease they have. And that is now a key goal for autoimmune research. We have to learn how to group and stratify patients so we can give them the right therapy.

Lee also stressed that surging cases of autoimmune diseases across the world meant new treatments and drugs were now urgently needed more than ever before. At present, there are no cures for autoimmune diseases, which usually develop in young people while they are trying to complete their education, get their first job and have families, he said.

That means growing numbers of people face surgery or will have to have regular injections for the rest of their lives. It can be grim for patients and a massive strain on health services. Hence the urgent need to find new, effective treatments.

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Global spread of autoimmune disease blamed on western diet - The Guardian