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Category Archives: Transhuman News
Scientists Just Surgically Removed HIV DNA From Live Animals – Futurism
Posted: May 6, 2017 at 3:15 am
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Recent estimates by the United Nationssay as many as 36.7 million peopleworldwide are known to have HIV.Of these, roughly 1.2 million people are in the United States, according to the Centers for Disease Control and Prevention (CDC). These alarming numbers actually grow every year, and adequate treatment let alone a cure still seems a long way off. One of the major reasons thats so isbecause HIV as a disease is something of a tough nut to crack: the virus is capable of hiding itself in latent reservoirs, making it extremely difficult for a permanent cure to be developed.
Theres a glimmer of hope, though: scientists atthe Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh published astudy in the journal Molecular Therapyshowing itspossible to surgically remove HIV DNA from a living animal genome. This is the first time that such a method was demonstrated to be possible, and it could increase the chances of eliminating HIV infection.
The secret is in CRISPR/Cas9, the worlds most efficient and effective gene editing tool, which made it possible to delete targeted HIV-1 fragments from the infected animal tissue genome. CRISPR-associated protein 9 (Cas9)-mediated genome editing provides a promising cure for HIV-1/AIDS, the studys abstract notes. This research built on a proof-of-concept study that the same team of researchers conductedlast year.
Our new study is more comprehensive, LKSOMs Wenhui Hu explained. We confirmed the data from our previous work and have improved the efficiency of our gene editing strategy. We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells.
The researchers used CRISPR/Cas9 to shut down HIV on three sets of animal models: one performed ontransgenic mice with HIV-1, another with mice acutely infected with the mouse equivalent of human HIV (ecoHIV), and a third group of mice that had human immune cells with latent HIV-1 embedded into their tissues and organs.
In all three animal models, the researchers were able to successfully render HIV inactive via gene editing, reducing the RNA expression of viral genes by up to 95 percent in the first model, and up to 96 percent in the second. For the third model, they were able to remove viral fragments from the latently infected human cells in the mouse organs after only a single CRISPR/Cas9 treatment.
Now, researchers need tomake the treatment more viable for humans:The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells, said researcher Kamel Khalili. Our eventual goal is a clinical trial in human patients.
As this is the first time gene editing was demonstrated to work on HIV in animals, this method could prove to be a game changer in treating the elusive virus: its a crucial step in, eventually,creating a cure.
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Child rapist gives DNA to cops, gets nabbed in 1993 sex assault … – New York’s PIX11 / WPIX-TV
Posted: at 3:15 am
New York's PIX11 / WPIX-TV | Child rapist gives DNA to cops, gets nabbed in 1993 sex assault ... New York's PIX11 / WPIX-TV HAMILTON HEIGHTS, Manhattan A man who pled guilty earlier this year to raping a child has just been tied, through DNA evidence, to the 1993 knifepoint ... Decades-Old Rape of 11-Year-Old Girl Solved With DNA Evidence ... DNA Evidence Links Man To Unsolved Rape From 1993, Manhattan ... DNA links NYC child rapist to young girl's 1993 cold case sexual ... |
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New capabilities for genome-wide engineering of yeast – Science Daily
Posted: at 3:14 am
New capabilities for genome-wide engineering of yeast Science Daily "The goal of the work was really to develop a genome-scale engineering tool for yeast . . . traditional metabolic engineering focused on just a few genes and the few existing genome-scale engineering tools are only applicable to bacteria, not ... |
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Scientists reveal new and improved genome sequence of Daphnia pulex – Phys.Org
Posted: at 3:14 am
May 5, 2017 by Jessica Sieff By understanding how species of Daphnia respond to toxic elements like industrial contaminants, toxic algae blooms or thermal stress, scientists can look at how environmental changes caused by agriculture and road runoff or warming temperatures and climate change could impact populations in lakes, rivers and standing bodies of water. Credit: Matt Cashore/University of Notre Dame
For many, experience with Daphnia, commonly known as water fleas, ends in high school. The organism is often used for science experiments exploring water toxicity, because of its sensitivity to environmental factors. But the tiny, transparent microcrustaceans have been studied intensively for more than 150 years, and new research published and featured on the cover of the journal G3 reveals scientists can now take a closer look at its genome.
Researchers have completed a new and improved genome sequence of Daphnia pulex (D. pulex), providing a clearer roadmap of the organism's genome so they can identify the genes and pathways that make this organism so successful in freshwater ecosystems.
Populations of Daphnia, barely visible to the naked eye, can be found in virtually every standing body of water on the planet, including Antarctica. They evolve quickly and are masters of responding to the conditions in their environment. Sensing the chemical cues of nearby predators, some species of Daphnia develop elaborate defensive structures such as spines and helmets that make them harder to eat. While scientists have gained a thorough understanding of what these tiny water fleas do to adapt to varying conditions, they don't yet know how they do it.
"That's why a system like this is so powerful," said Michael E. Pfrender, director of the Genomics & Bioinformatics Core Facility and associate professor in the Department of Biological Sciences and the Environmental Change Initiative at the University of Notre Dame. "We need this genomic infrastructure to add to the ecological context we already have to gain a better understanding of how Daphnia adapt. Because we have an improved genome sequence, we can get a more accurate catalog of genes and when thinking about response to the environment and chemical cues, it's the turning on and off of genes and pathways that's important. The picture is much more complete than it was before."
Calling it the "Portland Arch" genome after the Indiana Nature Preserve where the Daphnia was collected, the new assembly comes six years after the first sequence of D. pulex in 2011. The current study describes how scientists used the latest technology as part of a thorough and methodical process the result of which led to the identification of 18,440 genes.
D. pulex plays a vital role in Earth's ecology. Feeding off of algae and phytoplankton in standing freshwaters, they are the primary grazer in those environments, the "cows of lakes," said Pfrender. They're also primary forage, transferring all of that energy to the fish that eat them. By understanding how species of Daphnia respond to toxic elements like industrial contaminants, toxic algae blooms or thermal stress, scientists can look at how environmental changes caused by agriculture and road runoff or warming temperatures and climate change could impact populations in lakes, rivers and standing bodies of water.
"What happens to this vital part of the ecosystem when conditions change very rapidly? What genes allow some populations to cope with these changes while others fail?" Pfrender said. "That's what we want to find out. This genome sequence provides the toolkit."
Explore further: Study of the evolution of the micro-crustacean group Cladocera
More information: Zhiqiang Ye et al. A New Reference Genome Assembly for the Microcrustacean, G3: Genes|Genomes|Genetics (2017). DOI: 10.1534/g3.116.038638
Scientists of the Senckenberg Institute have studied the evolutionary history of the so-called "water fleas." These tiny crustaceans from the order Cladocera form the basis of the trophic pyramid and therefore play an important ...
Water fleas can thwart their enemies by growing defensive structures such as helmets and spines. What's more, this predator-induced 'arming' process is not a one-size-fits-all approach - they can even tailor their defensive ...
A common species of zooplanktonthe smallest animals in the freshwater food webcan evolve genetic tolerance to moderate levels of road salt in as little as two and a half months, according to new research published online ...
The key to helping animals evolve quickly in response to climate change could actually be their predators, according to a new UBC study.
A University of Michigan biologist combined the techniques of "resurrection ecology" with the study of dated lake sediments to examine evolutionary responses to heavy-metal contamination over the past 75 years.
There are many different kinds of crustaceans, ranging from the shellfish Swedish people eat at traditional crayfish parties every August to tiny relatives found in their millions in both freshwater and saltwater. One of ...
Much is known about flu viruses, but little is understood about how they reproduce inside human host cells, spreading infection. Now, a research team headed by investigators from the Icahn School of Medicine at Mount Sinai ...
For many, experience with Daphnia, commonly known as water fleas, ends in high school. The organism is often used for science experiments exploring water toxicity, because of its sensitivity to environmental factors. But ...
Researchers in dermatology at Lund University in Sweden believe they have cracked the mystery of why we are able to quickly prevent an infection from spreading uncontrollably in the body during wounding. They believe this ...
Vladimir Lukhtanov, entomologist and evolutionary biologist at the Zoological Institute in St. Petersburg, Russia, made a startling discovery: what people had thought was a population of a common species, turned out to be ...
(Phys.org)A team of researchers with the Howard Hughes Medical Institute has found that a ring of cells in the middle of the fruit fly brain acts as a compass, helping the insect understand where it is, where it has been ...
New research helps answer a long-standing mystery of how honeybees sense the size and strength of their colony, a critical cue for the bees to switch from investing solely in survival to also investing in reproduction.
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The Tea Plant’s Genome Has Been Unlocked – And It’s 4 Times That of Coffee – ScienceAlert
Posted: at 3:14 am
From a single species of plant comes many teas. The tea tree, a shrub called Camellia sinensis, produces white, green, black and oolong teas. The tea's destiny is a matter of variables.
The final drink reflects the tea cultivar, the growing environment and how the leaves are processed - dried, crushed, steamed, blended. Farmers pluck 'baby' leaves, as one Snapple commercial put it in the mid-2000s, to begin making white tea.
And yet scientists in China, South Korea and the United States say there is another way to further tea's potential, beyond altering the dirt or the stages of harvest or processing.
DNA analysis could lead to "a more diversified set of tea flavours" by tracing the genes responsible for taste, according to Lizhi Gao, a botany professor at the Chinese Academy of Sciences' Kunming Institute of Botany.
He and colleagues have completed the "first high-quality" genome of the tea tree shrub, published this week in the journal Molecular Plant.
The plant took five years to analyse, thanks to the sheer number of DNA sequences involved.
"The tea tree genome is extremely large," Gao wrote in an email to The Washington Post - counting 3 billion base pairs, about four times the size of coffee's genome.
Of hot and invigorating drinks, coffee gets most of the buzz, at least in the United States: this country is home to 140 million daily coffee drinkers and the Starbucks Unicorn Frappuccino, and Americans consume more coffee than people anywhere else.
Researchers sequenced the genome of robusta coffee in 2014, hinting at a future of genetically modified coffees, as The Post reported at the time.
Scientists followed up with the arabica coffee genome in January.
Monday marked the tea tree's turn. It was a long time coming. Dried plants, recently found in a Chinese mausoleum, revealed that emperors in the Han Dynasty enjoyed tea 2,100 years ago, possibly as part of a soup.
The sovereigns were onto something. Today, 3 billion people drink tea, and by one estimate, for every mug of coffee consumed on the planet, humans drink three cups of tea.
Gao and his colleagues had to churn through the tea tree's huge levels of retrotransposons. These repeated DNA sequences, about 80 percent of the tea genome, duplicated themselves into the genome again and again over 50 million years of tea tree evolution.
"It is a mystery why retrotransposon sequences are abundant in this plant but not in another," Gao said.
But the researchers were most interested not in size but in the way tea produces tasty molecules.
"The tea-processing industries in tea-drinking countries, especially in China, have developed numerous tea products with diverse tea flavour," Gao said.
But processing techniques alone aren't enough, he said. Tea also depends on developing new plant varieties, containing unique combinations of flavourful molecules.
Three types of chemicals are most responsible for tea's taste. One is an amino acid only found in tea, called l-theanine, which in the last decade has been added to drinks that promote focus and concentration. (Such focus drinks are of dubious efficacy and lack supporting research.)
The second type of chemical is a class of flavonoid, or plant pigment molecule, called catechins. The third is caffeine, which evolved in tea independently of cacao and coffee, akin to the way both sea turtles and dolphins evolved flippers separately.
There are several theories as to why plants produce caffeine. Caffeine at high doses is a natural pesticide. But at low doses, as in some nectars, it may be giving insects a memorable jolt.
Caffeine was one tool in tea's repertoire of "disease defense and environmental stress tolerance" methods to help it adapt globally to diverse habitats, Gao said.
The tea genome answered a question the scientist had long pondered: Why can't we make tea from close Camelliasinensis cousins, such as the tea oil plant Camellia oleifera?
It turns out that C. oleifera and its 100 other Camellia relatives do not produce high amounts of the caffeine or catechin family of genes. (Caffeine and catechins are not proteins but secondary metabolites, which means many genes are required to construct them.)
Put another way, Gao said, the expression levels of caffeine- and catechin-related genes "determines the tea processing suitability".
The chief horticulturist at Britain's Royal Horticultural Society, Guy Barter, said plant breeders would welcome this work.
"Once you understand the basis for the flavours and the processing quality of the tea, you can then have genetic markers that breeders can look for when trying to produce new varieties," he told the BBC.
2017 Washington Post
This article was originally published by The Washington Post.
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Towards India’s own standard genome sequence – Telangana Today
Posted: at 3:14 am
Indian company to collect genomic code of 1 lakh Asians, including over 30,000 Indians from various parts of the country
Hyderabad: Imagine a repository of over 30,000 Indian genomes covering a wide variety of groups from various regions and ethnic backgrounds accessible to researchers and healthcare providers.
Such a large Indian genomic data will not only enable researchers in finding the patterns of how genes are expressed but also can help in spotting mutations, which could be the answer for personalized therapy protocols for cancer patients, cardio-vascular ailments, end-stage kidney ailments and many more.
An Indian company along with several others in Asia has taken up this amibtious project to collect the genomic code of a whopping 1 lakh Asians, which also includes over 30,000 Indians from various parts of the country.
In the past, there have been isolated attempts at finding genomic sequence of one or two Indian groups but this is for the first time that a concerted effort is being taken up to collect the genome sequence of such a large set of population.
Standard genome Indian researchers need to have access to standard Indian genomic data to isolate the genes responsible for causing ailments among Indians. Almost all the medical standards, for instance ideal BP levels, sugar levels or anything else is based on Caucasian population. In the coming years, we intend to sequence genome of Indians and hopefully reach towards a standardized Indian genome, says CEO (India), MedGenome, Girish Mehta.
Talking to Telangana Today, Mehta said that MedGenome, a Bengaluru-based company, has already committed US$ 10 million for the project. The overall cost of the 1 lakh Asian genome is close to Rs. 100 crore or over 120 million US dollars.
We are collaborating with Singapore and South East Asian biotech companies to take part in preparing this genomic sequence. This will be very important because we will not only get to know the standard Indian genome but also the Asian genomic sequence, which is vital to form new treatment protocols, Mehta said, during a visit to Hyderabad.
Back in 2014, the United Kingdom had launched its own 1 lakh genome project and similar projects are under way in Qatar, Europe and the US.
Unfortunately, we are second largest population but we still do not have our own standard genome code. Earlier, genome sequencing of a single human being was very expensive but technology is rapidly making it very affordable. This is a four-year project and hopefully it should be completed in time, Mehta added.
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Molecular study of skin proteins uncovers predisposition to eczema … – Medical News Today
Posted: at 3:13 am
New research shows for the first time that a lack of the key barrier protein filaggrin alone may be responsible for changes in skin proteins and pathways that make people susceptible to eczema. It builds on previous work that shows a lack of the protein is strongly tied to the development of eczema.
Researchers from Newcastle University in the United Kingdom and Stiefel - a GlaxoSmithKline company - report their findings in the Journal of Allergy and Clinical Immunology.
Lead investigator Nick Reynolds, a professor of dermatology at Newcastle University who also works as a skin and eczema specialist in Newcastle's Royal Victoria Infirmary, says that their discovery "reinforces the importance of filaggrin deficiency leading to problems with the barrier function in the skin and predisposing someone to eczema."
He and his colleagues also believe that the study could lead to the development of drugs that target the underlying causes of eczema rather than just alleviate the symptoms.
Eczema is a condition that is usually characterized by dry, itchy, cracked, and rough skin that mainly erupts on the hands, feet, and face, as well as behind the knees and inside the elbows.
It can also present with blisters that weep fluid when scratched. The condition can cause disturbed sleep and may profoundly affect quality of life.
The most common type of eczema is an inflammatory, non-contagious skin condition called atopic dermatitis that affects around 30 percent of people in the United States, most of them children and adolescents.
In this article, the word eczema refers specifically to atopic dermatitis.
The exact causes of eczema are unknown. However, research reveals that it is likely to arise from a combination of genetic and environmental factors and probably involves dysfunction of both the skin barrier and the immune system. People with eczema may also develop asthma and hay fever.
Fast facts about eczema
Learn more about eczema
In their study report, the researchers explain that filaggrin plays a key role in maintaining the barrier that protects the skin and that previous research has already established that a lack of the protein strongly predisposes people to eczema.
However, exactly what happens at the molecular level to link filaggrin deficiency to the development of eczema "remains incompletely understood," they note.
To further investigate the role of filaggrin, the researchers developed a 3-D model of human skin, in which, using molecular tools, they made the epidermis (the outside layer) deficient in filaggrin.
The model closely mimics what happens in the skin of people with eczema.
Using the model, the researchers were able to map the proteins and signaling pathways that lie "downstream" of filaggrin, and thus observe how the absence of the protein altered them.
They identified a number of signaling mechanisms that regulate inflammation, cell structure, stress response, and the function of the skin barrier.
The mapping of these pathways in the model appears to match that seen in people with eczema.
For example, the skin of people with active eczema has high levels of a protein coded by the gene KLK7. The team was able to show - from the model - that upregulation of KLK7 was one of the molecular consequences of filaggrin loss.
"This type of research allows scientists to develop treatments that target the actual root cause of the disease, rather than just managing its symptoms. Given the level of suffering eczema causes, this is a pivotal piece of research."
Nina Goad, British Association of Dermatologists
Learn how friendly skin bacteria keep harmful Staphylococcus aureus in check.
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Prevent an eczema flare-up by avoiding these 8 things – Fox News
Posted: at 3:13 am
Derived from the Greek language, the word eczema translates to something like to boil. And anyone who has atopic dermatitis the most common form of eczema can probably see why. The symptoms often shows up as red, itchy rashes on your arms and legs, and can sometimes cause open sores or resemble scaly skin.
Although its possible to develop atopic dermatitis for the first time as an adult, the majority of people experience it shortly after they were born, perhaps as young as two months old. Most people outgrow it in their early teens, but it can come back later in life, says Whitney High, MD, an associate professor of dermatology and pathology at the University of Colorado School of Medicine, in Denver. For some people, atopic dermatitis continues through into adulthood and never lets up.
The condition itself is likely hereditary, and usually runs in the same circles as allergic rhinitis and asthma. Families that have one child with eczema often have another child with asthma or even a third child with seasonal rhinitis or hay fever, he says.
To limit your odds of experiencing a flare-up, here are nine things to avoid.
1. Taking a luxurious bath A long soak in the tub might sound fantastic but if you have atopic dermatitis, spending too long in the bathtub can leave your skin feeling itchy and red. The next time you turn on the tap, remember the Goldilocks rule: the water should be not too hot, not too cold, but a lukewarm medium. Ideally, youll also limit your soak to no longer than 15 minutes a day, says Dr. High. We tell people to take good care of their skin by doing gentle bathing and not over-drying the skin, he says.
RELATED: The 7 best lotions for eczema, according to dermatologists
2. Wearing a wool sweater Any kind of abrasive texture, like wool or certain synthetic fibers, might irritate your skin, says Dr. High. A better wardrobe choice: soft, cotton clothing in a looser cut, which wont rub against your skin. You should also wash any new clothing you buy before wearing them some contain dyes that make the fabric appear nicer in the store, but may trigger a flare-up on your skin.
3. Using scented laundry detergents Scented laundry detergents and some dryer sheets can also bother your skin. Choose products that are free of fragrances and dyes; liquid ones tend to leave less irritating residues behind compared to powder versions. We like the all-FREE CLEAR laundry detergent thats specifically designed for people with sensitive skin; the product received a seal of acceptance from the National Eczema Association (NEA), which keeps a list of other helpful products on their website.
RELATED: The best laundry detergents for sensitive skin
4. Washing with anything besides fragrance-free soaps Similar to scented laundry detergents, scented hand soaps, bubble baths, body washes, and lotions can all cause your skin to feel dry and itchy. Use bland soaps, not highly perfumed or scented soaps, says Dr. High.
5. Scratching your skin Atopic dermatitis is sometimes called the itch that rashes. In other words, says Dr. High, some people think you have the itching sensation first, then do all the damage to the skin with the scratching and picking, which leads to the rash. And while its a good idea to reach for a moisturizer at the first sign of a tingle, you should also keep your fingernails trimmed and smooth that way, youll be less likely to puncture the skin if you do end up scratching at it.
6. Getting too hot or cold During the warmer months, the high temperatures (or, the sensation of heat, says Dr. High) can sometimes bother peoples skin. Not only that, but sweating can cause irritation, too. Likewise, the cold, dry weather in winter can also trigger itchiness.
7. Skipping moisturizer To avoid a flare-up, youll have to do more than just avoid certain products. You should also moisturize your skin at least twice a day to prevent it from becoming too dry or cracked, according to the American Academy of Dermatology. Look for mild, fragrance-free lotions Aveeno Eczema Therapy Moisturizing Cream and Cetaphils RestoraDerm Eczema Calming Body Moisturizer are two options or opt for petroleum jelly. Its also smart to try out a new product on a small area of your skin first, on the off chance that it causes your skin to feel itchy and irritated later on.
Although the majority of eczema flare-ups arent caused by a persons diet, there may be occasional cases where atopic dermatitis is exacerbated by food or drinks, says Dr. High. To pinpoint what might be triggering your flare, try keeping track of your daily routine (including meals) in a journal. By looking back at your past entries, you might be able to identify the culprits. For example, if you and your doctor think that milk is causing a flare, you might want to eliminate it from your diet while working with a nutritionist to help shore up your intake with other calcium-rich foods.
8. Letting stress take over Although stress can certainly trigger a flare, Dr. High says that its usually the last factor that doctors consider. But he also notes that all of his patients feel itchier at night, whether they have atopic dermatitis or any other itching skin condition. Its the time of the day when its quiet, says Dr. High. Youre not going to feel itchy when youre going a million miles an hour at your job. You dont have time to plug into all those body sensations.
This article originally appeared on Health.com.
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Understanding genetic variations in black women could improve cancer outcomes – UChicago News
Posted: at 3:11 am
Although the odds of developing breast cancer are nearly identical for black and white women, black women are 42 percent more likely to die from the disease. This mortality gapdriven by social and environmental, as well as biological factorscontinues to persist.
A large, multi-institutional study, published May 4 in JAMA Oncology, was designed to understand this gap by beginning to unravel the germline genetic variations and tumor biological differences between black and white women with breast cancer. This is the first ancestry-based comprehensive analysis of multiple platforms of genomic and proteomic data of its kind, the authors note.
Findings from this study could lead to more personalized risk assessment for women of African heritage and hasten the development of novel approaches designed to diagnose specific subtypes of aggressive breast cancers early and treat them effectively.
One new finding is that black women with hormone receptor positive, HER2-negative breast cancer had a higher risk-of-recurrence score than white women. The study also confirmed that black patients were typically diagnosed at a younger age and were more likely to develop aggressive breast-cancer subtypes, including basal-like or triple-negative cancerstumors lacking estrogen receptors, progesterone receptors and HER2as well as other aggressive tumor subtypes.
People have long associated breast cancer mortality in black women with poverty, or stress, or lack of access to care, but our results show that much of the increased risk for black women can be attributed to tumor biological differences, which are probably genetically determined, said study author Olufunmilayo Olopade,the Walter L. Palmer Distinguished Service Professor in Medicine and Human Genetics at the University of Chicago.
The good news, she said, is that as we learn more about these genetic variations, we can combine that information with clinical data to stratify risk and better predict recurrencesespecially for highly treatable cancersand develop interventions to improve treatment outcomes.
This is a great example of how team science and investments in science can accelerate progress in identifying the best therapies for the most aggressive breast cancers, said co-author Charles Perou, a member of the University of North Carolina Lineberger Comprehensive Cancer Center and professor of genetics, and pathology & laboratory medicine at the UNC School of Medicine.
In the largest dataset to date that has good representation of tumors from black women, we did not find much difference between the somatic mutations driving tumors in black and white women, he added. Yet black women were more likely to develop aggressive molecular subtypes of breast cancer. Now we provide data showing that differences in germline genetics may be responsible for up to 40 percent of the likelihood of developing one tumor subtype versus another.
The study used DNA data collected from 930 women154 of predominantly African ancestry and 776 of European ancestryavailable through The Cancer Genome Atlas, established by the National Cancer Institute and the National Human Genome Research Institute. The researchers combed through the data methodically, looking for racial differences in germline variations, somatic mutations, subtypes of breast cancers, survival time, as well as gene expression, protein expression and DNA methylation patterns.
Most significantly, explained first author Dezheng Huo, associate professor of public health sciences at the University of Chicago, we observed a higher genetic contribution to estrogen-receptor negative breast cancer in blacks.
Black women were more likely to get these highly aggressive cancers. This is one of the first studies to connect genetics to this racial difference in tumor subtype frequencies.
The study also revealed 142 genes that showed differences in expression levels according to race. One gene, CRYBB2, was consistently higher in tumors from black patients within each breast cancer subtype, as well as in normal tissues, suggesting it may be a race-specific gene.
The researchers also found somatic mutations in 13 genes or DNA segments that differed in frequency in tumors from black and white women. One of them, a mutated gene called TP53, was more common in black women than white women and was a strong predictor of disease recurrence.
Despite the relatively short follow-up time in the TCGA dataset, we were able to detect a significant racial disparity in patient survival using breast cancer-free interval as the endpoint between patients of African and European ancestries, said co-first author Hai Hu, vice president for research at the Chan Soon-Shiong Institute of Molecular Medicine at Windber. Most of the worst outcomes came from basal-like subtype breast cancer patients of African Ancestry.
Black women in all categories, including the most common breast cancers, were likely to have a worse prognosis, Olopade said.
Understanding the basic, underlying genetic differences between black and white women, the higher risk scores and the increased risk of recurrence should lead us to alternative treatment strategies, said Perou.
The crucial long-term benefit of this study, according to Olopade, is that it is a step toward the development of polygenic biomarkers, tools that can help us better understand each patients prognosis and, as we learn more, play a role in choosing the best treatment.
Genes matter, she added. This is a foot in the door for precision medicine, for scientifically targeted treatment.
This study now outlines a path for us to personalize breast cancer risk assessment and develop better strategies to empower all women, especially black women, to know their genetics and be more proactive in managing their risk, Perou said.
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Understanding genetic variations in black women could improve cancer outcomes - UChicago News
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Potential New ALS Gene Leads to Extraordinary Aggregates – Alzforum
Posted: at 3:11 am
05 May 2017
A paper in the May 3 Science Translational Medicine identifies a potential new risk gene for amyotrophic lateral sclerosis (ALS). Mutations in ANXA11, which encodes the phospholipid binding protein annexin A11, turned up in people with both familial and sporadic forms of the disease, report scientists led by Christopher Shaw of Kings College London, Vincenzo Silani of the University of Milan, and John Landers of the University of Massachusetts Medical School, Worcester. Mutant proteins strayed from their normal binding partner, the calcyclin protein, and instead aggregated in the nucleus and cytoplasm. Annexin A11 appears to aid in vesicletransport.
This falls in line with themes we are seeing in all ALS mutations, which are impairments in proteostasis, autophagy, vesicular trafficking, and aggregation, said Matthew Harms, Columbia University, New York. It adds some genetic firepower to our interest in thosepathways.
Mutant annexin A11 inclusions take varied forms, including an ordered series of parallel tubules seen from the side (left) and top. [Courtesy of Science TranslationalMedicine/AAAS.]
This paper lists a handful of co-first authors: Bradley Smith, Simon Topp, and Han-Jou Chen of Kings College, with Claudia Fallini of UMass Worcester, and Hideki Shibata, Nagoya University, Japan. On their hunt for new ALS-associated genes, they analyzed whole exome sequences from 751 patients with familial disease and from 180 with sporadic ALS. They found six rare mutations in annexin A11 in 13 people, including a p.D40G amino acid substitution that segregated with disease in two families. These mutations were absent from 70,000 healthy controls. They clustered at the N-terminal tip of the protein. Previous studies suggest that annexin A11 aids in vesicular transport between the endoplasmic reticulum and Golgi apparatus (Shibata et al., 2015).
Carriers developed ALS at an average age of 67, with a classic ALS phenotype and primarily bulbar-onset disease, meaning they first had trouble speaking and swallowing. One patient who had the p.D40G mutation donated tissue for postmortem analysis. As is typical in ALS, neuron loss, astrogliosis, and phosphorylated TDP-43 inclusions pervaded their spinal cords; the latter also appeared in the medulla, temporal neocortex, andhippocampus.
The surprise came when the researchers stained for annexin A11. We saw the most extraordinary inclusions, Shaw told Alzforum. The skein-like patterns and tubular structures in motor neurons of the spinal cord were a far cry from the disordered blobs of TDP-43 that are typical of ALS neuropathology. They were unlike anything the scientists had ever seen, Shaw said (see image above). Add to that the torpedo-shaped structures in axons of the motor cortex, temporal neocortex, and hippocampus, and Shaw knew they were onto something. This mutant protein is actually aggregating in our patients, he said. That gave me 100 percent confidence that we had found a real gene causingpathology.
To find out how ANXA11 causes disease, the authors expressed several of the disease-associated variants or the wild-type protein in mouse primary motor neurons. Wild-type annexin A11 appeared in the nucleus, and in large, vesicle-like structures throughout the cytoplasm of the axons, soma, and dendrites. By contrast, the mutant proteins largely stayed out of vesicles; they aggregated instead. Their inclusions trapped functional, wild-type annexin A11 protein, implying they robbed the cell of the function of the normalprotein.
The variants also appeared to disrupt Annexin A11 binding to calcylin. Computer modeling predicted that the N-terminus of annexin A11 forms two helices, one in and the other next to the calcyclin binding site. Two of the six mutations appeared to disrupt formation of one of those helices. Immunoprecipitation assays revealed that while wild-type annexin A11 bound calcyclin, those mutants did not. The authors suggested that when annexin A11 cannot bind calcyclin, annexin A11 builds up in the cytoplasm and accumulates. As controls, the authors expressed non-pathogenic annexin A11 variants that appear in the general population; these variants left calcyclin bindingintact.
That last step was important, and provides a model for how these assays should be done in the future, said Harms, adding, It demonstrated that the ALS-specific functional defect was coming from mutations that they found in the patients. In general, researchers should always compare suspected pathogenic mutations to non-pathogenic ones to avoid assays picking up on nonspecific effects. Harms agreed this paper offers clear evidence that the p.D40G mutationwhich segregates with disease and leads to those unusual inclusionsis causative of ALS. More work needs to be done to see if the other five mutations are pathogenic, hesaid.
Shaw said his collaborators are now making transgenic zebrafish and mouse models with the mutations so they can study them in whole organisms.Gwyneth DickeyZakaib
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Potential New ALS Gene Leads to Extraordinary Aggregates - Alzforum
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