Author Archive for Pharmboy

Gene-editing technique CRISPR identifies dangerous breast cancer mutations

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Gene-editing technique CRISPR identifies dangerous breast cancer mutations

File 20180912 181248 1b284hk.jpg?ixlib=rb 1.1

Breast cancer type 1 (BRCA1) is a human tumor suppressor gene, found in all humans. Its protein, also called by the synonym BRCA1, is responsible for repairing DNA. ibreakstock/Shutterstock.com

By Jay Shendure, University of Washington; Greg Findlay, University of Washington, and Lea Starita, University of Washington

More than 1 million women have had genetic testing of BRCA1 and BRCA2, genes in which mutations can dramatically increase the risk for early onset breast and ovarian cancer. But for many women the test results have been ambiguous. That’s because it’s not clear where certain genetic variations are harmless or cause cancer.

BRCA1 was amongst the first cancer predisposition genes discovered, and it has been studied for over 20 years. The gene produces a protein that repairs DNA damage, which might otherwise lead to the formation of tumors. Since its discovery, researchers and clinicians have identified many genetic variations in BRCA1, but for most of these, we are unable to tell whether they impair function of the gene – raising the risk of cancer – or whether they are perfectly harmless.

Our research team works in the emerging field of genomic medicine, which uses an individual’s genetic information to prescribe care. We recognized that such “variants of uncertain significance” limited the utility of genetic testing and the prospects for genomic medicine. We know that problem is likely to get worse, as the number of uncertain variants in BRCA1 and other “medically actionable” genes is expected to grow exponentially as genetic testing is expanded to entire populations.

In a study, we set out to apply CRISPR genome editing to solve the challenge posed by these variants of uncertain significance. CRISPR has tremendous potential because the technology allows researchers like us to tinker with human genes. CRISPR allows us to make very specific changes, “edits” to our DNA – thus the phrase, “genome editing.”

Although there are many studies that are attempting to use CRISPR to treat disease, it can also be used to introduce specific mutations into human cells that grow in a dish,…
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Cracking the sugar code: Why the ‘glycome’ is the next big thing in health and medicine

 

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Cracking the sugar code: Why the 'glycome' is the next big thing in health and medicine

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By molekuul_be/shutterstock.com

Courtesy of Emanual Maverakis, University of California, Davis; Carlito Lebrilla, University of California, Davis, and Jenny Wang, Yeshiva University

When you think of sugar, you probably think of the sweet, white, crystalline table sugar that you use to make cookies or sweeten your coffee. But did you know that within our body, simple sugar molecules can be connected together to create powerful structures that have recently been found to be linked to health problems, including cancer, aging and autoimmune diseases.

These long sugar chains that cover each of our cells are called glycans, and according to the National Academy of Sciences, creating a map of their location and structure will usher us into a new era of modern medicine. This is because the human glycome – the entire collection of sugars within our body – houses yet-to-be-discovered glycans with the potential to aid physicians in diagnosing and treating their patients.

Thanks to the worldwide attention garnered by the 2003 completion of the Human Genome Project, most people have heard about DNA, genomics and even proteomics – the study of proteins. But the study of glycans, also known as glycomics, is about 20 years behind that of other fields. One reason for this lag is that scientists have not developed the tools to rapidly identify glycan structures and their attachment sites on people’s cells. The “sugar coat” has been somewhat of a mystery.

Until now, that is.

While most laboratories focus on cellular or molecular research, our lab is dedicated to developing technology to rapidly characterize glycan structures and their attachment sites. Our ultimate goal is to catalog the hundreds of thousands of sugars and their locations on various cell types, and then to use this information to tailor medical therapies to each individual.

Why do we care about glycans?

In the future, it is likely that analysis of an individual’s glycans will be used to predict our…
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Diabetes: new test could detect the disease much earlier

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Diabetes: new test could detect the disease much earlier

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Egoreichenkov Evgenii/Shutterstock.com

Courtesy of Samuel Virtue, University of Cambridge

The glucose tolerance test is the standard method for detecting diabetes. But our new study suggests that a different test can identify the disease earlier than the glucose tolerance test.

Diabetes kills 3.4m people worldwide each year, and this figure is expected to continue rising. It kills people by causing secondary diseases, such as heart disease, stroke and kidney failure. And the longer diabetes remains untreated, the greater the risk of developing these diseases, so early detection is vital.

Diabetes is detected when the body can no longer regulate its own blood sugar levels. Blood sugar is controlled by insulin, a hormone made in the pancreas. This hormone lowers blood glucose by making the body’s cells take it up, where it is stored or used for energy.

VectorMine/Shutterstock.com

There are two major forms of diabetes: type 1 and type 2. Type 1 is an autoimmune disease where the body destroys the cells in the pancreas that produce insulin. Type 2 is a progressive disease where the body first becomes resistant to insulin. Initially, the body makes more insulin to keep blood sugar levels in check, but the pancreas then wears out and blood glucose levels become dangerously high.

Fat as the new marker

In type 2 diabetes, the body’s cells become resistant to the effects of insulin before diabetes develops. This made us wonder whether we could detect earlier stages of the disease, when the body is insulin resistant but before the pancreas has worn out and blood glucose levels have increased. We focused on investigating how the body becomes unresponsive to insulin. And to do so, we considered fat, not glucose.

Obesity is now established as the leading cause of type 2 diabetes. One of the main ways that obesity is thought to cause diabetes is by the body fat (adipose tissue) not working properly.…
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Approval of first ‘RNA interference’ drug – why the excitement?

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Approval of first ‘RNA interference’ drug – why the excitement?

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Single strands of ribonucleic acid (RNA) are now being used to treat disease. By nobeastsofierce / shutterstock.com

Courtesy of Thomas Schmittgen, University of Florida

Small interfering RNA sounds like something from a science fiction novel rather than a revolutionary type of medicine. But this odd-sounding new drug offers a novel strategy for treating disease by targeting the root cause rather than just the symptoms. This is an exciting approach because it enhances the effectiveness of the treatment and reduces side effects.

The Food and Drug Administration recently approved the very first therapeutic small interfering RNA (siRNA), Onpattro (patisiran), to treat nerve damage caused by a rare disease called hereditary transthyretin-mediated amyloidosis (hATTR). Hereditary transthyretin-mediated amyloidosis affects about 50,000 people worldwide. The major cause is the buildup of a protein called amyloid in the peripheral nerves, heart and other organs. Small interfering RNA was first described in 1998 and its discoverers were awarded the Nobel prize in physiology or medicine in 2006. Twenty years later the discovery has been translated into a new form of medicine.

Proteins make up the largest structural and functional portion of our cells and tissues. The instructions to make a particular protein is encoded in our DNA. In order for the protein to be made, DNA must first be transcribed into an intermediate molecule called messenger RNA, which is then translated into a protein. Simply put, DNA makes RNA makes protein.

DNA encodes the instructions to make proteins. Inside the cell DNA is converted into RNA, which is then translated into a protein. By Fancy Tapis / shutterstock.com

A disease such as hATTR is caused by excessive amyloid protein. One solution to overcoming these defects is to limit the protein from being made in the first place.

That’s where siRNA comes in.

The beauty of RNA drugs like Onpattro lies in its specificity. Onpattro is a small stretch of RNA that “interferes” with its…
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Nanomedicine could revolutionise the way we treat TB. Here’s how

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Nanomedicine could revolutionise the way we treat TB. Here's how

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Nanomedicine could scupper the need for TB patients to take multiple daily tablets with toxic side effects. Daniel Irungu/EPA

Courtesy of Sarah D'Souza, University of the Western Cape and Admire Dube, University of the Western Cape

Tuberculosis is one of the world’s deadliest infectious disease. Worldwide, there are still about 10.4 million cases of TB and 1.7 million deaths every year.

One of the reasons it’s been hard to bring the disease under control is that the drugs used to treat it require a gruelling regimen and can be toxic. This means people very often don’t finish the course.

TB treatment lasts for six months and uses a combination of four antimicrobial drugs taken in large, daily amounts. The reason for the large daily dose is that these drugs are poorly absorbed; even when a drug gets to the infected site, only a portion of it will enter the affected tissue and fight the bacteria. They are also quickly eliminated from sites of infection by metabolic body functions.

These medicines also exhibit considerable toxicity such as liver damage, painful tingling in the hands and feet as well as joint pain. That’s because they don’t just target the infected areas of the body.

In some instances, the medicines are only available as injectables into the muscle, which is a painful procedure – and require daily clinic or prolonged hospital stays.

All of this leads to poor adherence to treatment among TB patients – and, ultimately, contributes to the generation and transmission of drug resistant TB strains. These are even harder to treat, with treatment lasting up to two years.

But there may be hope for TB treatment, in the form of nanomedicine. Tests are already being done on animals. And we are just two of many researchers from around the globe doing research at the nexus of nanomedicine and TB at the University of the Western Cape.

How nanomedicine works

Nanomedicine is the use of…
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Here’s what we know about CRISPR safety – and reports of ‘genome vandalism’

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Here's what we know about CRISPR safety – and reports of 'genome vandalism'

File 20180727 106505 1s3j5di.jpg?ixlib=rb 1.1

A standee of the movie ‘Rampage’ at a theater in Bangkok, Thailand. Scientists in the film used CRISPR to create a monster. By Sarunyu L/shutterstock.com

Courtesy of Jianhua Luo, University of Pittsburgh

A movie just recently released called “Rampage” features Dwayne “The Rock” Johnson using a genetic engineering technology called CRISPR, to transform a gorilla, among other animals, into a flying dragon-monster with gigantic teeth. Though this is science fiction, not to mention impossible, the movie captures the imagination of the public and their recent interest and fascination with CRISPR.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, was originally part of bacterial defense system that evolved to destroy foreign DNA that entered a bacterium. But this system was also capable of editing DNA – and now geneticists have honed the technology to alter the DNA sequences that we specify. This has generated enormous excitement and great expectations about the possibility of using CRISPR to alter genetic sequences to improve our health, to treat diseases, improve the quality and quantity of our food supplies, and tackle environmental pollution.

But a few recent scientific papers suggest that CRISPR is not without its problems. The research reveals that CRISPR can damage DNA that is far from the target DNA we are trying to correct. As a cancer biologist at the University of Pittsburgh School of Medicine, I use CRISPR in my lab to study human cancers and develop ways to kill cancer cells. Although the new finding appears significant, I don’t think that these revelations rule out using the technology in a clinical setting, but rather, they suggest we take additional cautionary measures as we implement these strategies.

Treating human diseases

CRISPR/Cas9 is being used to edit DNA in plants, animals, and in humans. But new studies are casting doubts about whether the technology is safe to use for human therapies. By TotallyMJ/shutterstock.com

Using genome editing…
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How summer and diet damage your DNA, and what you can do

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How summer and diet damage your DNA, and what you can do

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Bright sun and fatty foods are a bad recipe for your DNA. By Tish1/shutterstock.com

Courtesy of Adam Barsouk, University of Pittsburgh

Today, your body will accumulate quadrillions of new injuries in your DNA. The constant onslaught of many forms of damage, some of which permanently mutates your genes, could initiate cancer and prove fatal. Yet all is not doomed: The lives we lead determine how well our cells can handle this daily molecular erosion.

Certain cells are particularly at risk. Your skin, for instance, is constantly being bombarded by high-energy UV light that wreaks havoc on your DNA. This UV light should not be taken lightly — 1 in 5 Americans develops skin cancer in their lifetime, more than any other cancer. So as you’re hitting the beach with sugary margaritas in hand, remember that deadly skin cancer rates are at record-highs, as are cancers associated with obesity.

I am a medical student in Dr. Patricia Opresko’s lab at the University of Pittsburgh, which stands at the intersection of two Nobel Prize-winning disciplines: DNA repair and telomeres. Telomeres are protective regions at the ends of our chromosomes that hold the DNA together like the plastic cap on your shoelace. Her lab’s work is revealing the molecular machinery that repairs your telomeres after UV and metabolic (related to energy extraction from food) damage, and the many ways it can go awry.

Telomeres are protective caps on the end of chromosomes. By Fancy Tapis/shutterstock.com

Telomeres: Where chromosomes end and our research begins

In the minute you’ve been reading, hundreds of trillions of new lesions have occurred in your DNA. Fortunately, a special class of proteins is vigilantly detecting and repairing these errors.

Repair is particularly important in telomeres.

The telomere is no small thing, at least not figuratively: Their length is correlated with many symptoms of aging.…
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Opioids don’t have to be addictive – the new versions will treat pain without triggering pleasure

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Opioids don't have to be addictive – the new versions will treat pain without triggering pleasure

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shutterstock.

Courtesy of Tao Che, University of North Carolina – Chapel Hill

The problem with opioids is that they kill pain – and people. In the past three years, more than 125,000 persons died from an opioid overdose – an average of 115 people per day – exceeding the number killed in car accidents and from gunshots during the same period.

America desperately needs safer analgesics. To create them, biochemists like myself are focusing not just on the opioids, but on opioid receptors. The opioids “dock” with these receptors in the brain and peripheral nervous system dulling pain but also causing deadly side effects.

My colleagues and I in Bryan Roth’s lab have recently solved the atomic structure of a morphine-like drug interacting with an opioid receptor, and now we are using this atomic snapshot to design new drugs that block pain but without the euphoria that leads to addiction.

What has caused the opioid epidemic?

In the U.S., more than one-third of the population experiences some form of acute or chronic pain; in older adults this number rises to 40 percent. The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide.

To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone. Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR).

MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug. However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death.

Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem,…
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Mind molding psychedelic drugs could treat depression, and other mental illnesses

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Mind molding psychedelic drugs could treat depression, and other mental illnesses

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By agsandrew/shutterstock.com

Courtesy of David E. Olson, University of California, Davis

It seems that psychedelics do more than simply alter perception. According to the latest research from my colleagues and me, they change the structures of neurons themselves.

My research group has been studying the effects of psychedelics on neuronal structure and function, and we found that these compounds cause neurons to grow. A lot. Many of these compounds are well-known and include lysergic acid diethylamide (LSD), psilocin (from magic mushrooms), N,N-dimethyltryptamine (DMT, from ayahuasca) and 3,4-methylenedioxymethamphetamine (MDMA, aka ecstasy).

These are among the most powerful drugs known to affect brain function, and our research shows that they can alter the structure of the brain as well. Changes in neuronal structure are important because they can impact how the brain is wired, and consequently, how we feel, think and behave.

Prior to our study, there were relatively few compounds known to have such drastic and rapid effects on neuronal structure. One of those compounds was ketamine – a dissociative anesthetic and quite possibly the best fast-acting antidepressant that we have available to us at the moment.

If you think of a neuron like a tree, then its dendrites would be the large branches, and its dendritic spines – which receive signals from other neurons – would be the small branches. Some of these small branches might have leaves, or synapses in the case of a neuron. In fact, neuroscientists often use terms like “arbor” and “pruning” much like a horticulturist would. When we grew neurons in a dish – which is not unlike growing a plant in a pot – and fed them psychedelic compounds, the neurons sprouted more dendritic branches, grew more dendritic spines, and formed more connections with neighboring neurons.

The rainbow-colored neuron was treated with LSD, while the purple neuron was the control. LSD altered the structure of the neuron, allowing it to grow more branches


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We’re not prepared for the genetic revolution that’s coming

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We're not prepared for the genetic revolution that's coming

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Shutterstock

Courtesy of Robert Chapman, Goldsmiths, University of London

When humans’ genetic information (known as the genome) was mapped 15 years ago, it promised to change the world. Optimists anticipated an era in which all genetic diseases would be eradicated. Pessimists feared widespread genetic discrimination. Neither of these hopes and fears have been realised.

The reason for this is simple: our genome is complex. Being able to locate specific differences in the genome is only a very small part of understanding how these genetic variants actually work to produce the traits we see. Unfortunately, few people understand just how complex genetics really is. And as more and more products and services start to use genetic data, there’s a danger that this lack of understanding could lead people to make some very bad decisions.

At school we are taught that there is a dominant gene for brown eyes and a recessive one for blue. In reality, there are almost no human traits that are passed from generation to generation in such a straightforward way. Most traits, eye colour included, develop under the influence of several genes, each with its own small effect.

What’s more, each gene contributes to many different traits, a concept called pleiotropy. For example, genetic variants associated with autism have also been linked with schizophrenia. When a gene relates to one trait in a positive way (producing a healthy heart, say) but another in a negative way (perhaps increasing the risk of macular degeneration in the eye), it is known as antagonistic pleiotropy.

There’s no single gene for eye colour. Shutterstock

As computing power has increased, scientists have been able to link many individual molecular differences in DNA with specific human characteristics, including behavioural traits such as educational attainment and psychopathy. Each of these genetic variants only explains a tiny amount of variation in a population. But when all these variants are summed together (giving…
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Phil's Favorites

Theresa May's deal is almost exactly the Brexit the UK voted for

 

Theresa May’s deal is almost exactly the Brexit the UK voted for

Courtesy of Craig Berry, Manchester Metropolitan University

Forgive me, I may have missed something. There has of course been a lot to take in over the last few days. But, despite what the latest former Brexit secretary believes, it seems to me that the Brexit withdrawal agreement delivers almost exactly what the UK voted for in June 2016.

The reasons 17.4m people voted to leave the EU were mu...



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Kimble Charting Solutions

King Dollar Creating A Topping Pattern This Week?

Courtesy of Chris Kimble.

CLICK ON CHART TO ENLARGE

King Dollar has spent the majority of the past 7-years inside of rising channel (1), as it’s created a series of higher lows and higher highs.

The 2018 rally has it kissing the underside of potential resistance this week at (2), where it could be creating a bearish reversal pattern. This one week action has NOT changed the upward trend in King Dollar.

If it breaks rising support at (3), odds favor that some selling pressure takes place in the US$, which metals would lov...



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Zero Hedge

IMF Sounds The Alarm On Leveraged Lending

Courtesy of ZeroHedge. View original post here.

Five months after the IMF sounded the alarm over junk bonds, it has now moved on to the credit market bogeyman du jour and overnight joined others such as the Fed, BIS, Oaktree, JPMorgan, and Guggenheim in "sounding the alarm on leveraged loans."

By Tobias Adrian, ...



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Insider Scoop

Analysts Cautious On Williams-Sonoma After Q3 Print

Courtesy of Benzinga.

Related WSM 48 Stocks Moving In Friday's Mid-Day Session 28 Stocks Moving In Friday's Pre-Market Session ...

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Members' Corner

NY Times: OPERATION INFEKTION

 

This is a three-part Opinion Video Series from NY Times about Russia’s meddling in the United States’ elections as part of its "decades-long campaign to tear the West apart." This is not fake news. Read more about the series here.

OPERATION INFEKTION

RUSSIAN DISINFORMATION: FROM COLD WAR TO KANYE

By Adam B. Ellick and Adam Westbrook

EPISODE 1

MEE...



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Chart School

Weekly Market Recap Nov 11, 2018

Courtesy of Blain.

This past week was saw another positive move up by bulls – especially in the Dow and S&P 500; the NASDAQ was not quite as enthusiastic.   Wednesday’s rally was on the legs of an election that was seen as market friendly or at least not as bad as it could have been.   Essentially – paying people a lot of money to get nothing done the next 2 years – woo hoo!

The market is interpreting Wedneday’s result as insuring that “no big things will get done,” in Washington between now and 2020, Craig Birk, chief investment officer at Personal Capital told MarketWatch. “The market appreciates the relative certainty of the slow legislative agenda.” he said.

“As President Trump plans his 2020 reelection campaign, a gridlocked Congress is unlik...



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Digital Currencies

Bitcoin's high energy consumption is a concern - but it may be a price worth paying

 

Bitcoin's high energy consumption is a concern – but it may be a price worth paying

Shutterstock

Courtesy of Steven Huckle, University of Sussex

Bitcoin recently turned ten years old. In that time, it has proved revolutionary because it ignores the need for modern money’s institutions to verify payments. Instead, Bitcoin relies on cryptographic techniques to prove identity and authenticity.

However, the price to pay for all of this innovation is a high carbon footprint, created by Bitc...



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ValueWalk

Vilas Fund Up 55% In Q3; 3Q18 Letter: A Bull Market In Bearish Forecasts

By Jacob Wolinsky. Originally published at ValueWalk.

The Vilas Fund, LP letter for the third quarter ended September 30, 2018; titled, “A Bull Market in Bearish Forecasts.”

Ever since the financial crisis, there has been a huge fascination with predictions of the next “big crash” right around the next corner. Whether it is Greece, Italy, Chinese debt, the “overvalued” stock market, the Shiller Ratio, Puerto Rico, underfunded pensions in Illinois and New Jersey, the Fed (both for QE a few years ago and now for removing QE), rising interest rates, Federal budget deficits, peaking profit margins, etc...



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Biotech

Gene-editing technique CRISPR identifies dangerous breast cancer mutations

Reminder: Pharmboy is available to chat with Members, comments are found below each post.

 

Gene-editing technique CRISPR identifies dangerous breast cancer mutations

Breast cancer type 1 (BRCA1) is a human tumor suppressor gene, found in all humans. Its protein, also called by the synonym BRCA1, is responsible for repairing DNA. ibreakstock/Shutterstock.com

By Jay Shendure, University of Washington; Greg Findlay, ...



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Mapping The Market

Mistakes were Made. (And, Yes, by Me.)

Via Jean-Luc:

Famed investor reflecting on his mistakes:

Mistakes were Made. (And, Yes, by Me.)

One that stands out for me:

Instead of focusing on how value factors in general did in identifying attractive stocks, I rushed to proclaim price-to-sales the winner. That was, until it wasn’t. I guess there’s a reason for the proclamation “The king is dead, long live the king” when a monarchy changes hands. As we continued to update the book, price-to-sales was no longer the “best” single value factor, replaced by others, depending upon the time frames examined. I had also become a lot more sophisticated in my analysis—thanks to criticism of my earlier work—and realized that everything, including factors, moves in and out of favor, depending upon the market environment. I also realized...



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OpTrader

Swing trading portfolio - week of September 11th, 2017

Reminder: OpTrader is available to chat with Members, comments are found below each post.

 

This post is for all our live virtual trade ideas and daily comments. Please click on "comments" below to follow our live discussion. All of our current  trades are listed in the spreadsheet below, with entry price (1/2 in and All in), and exit prices (1/3 out, 2/3 out, and All out).

We also indicate our stop, which is most of the time the "5 day moving average". All trades, unless indicated, are front-month ATM options. 

Please feel free to participate in the discussion and ask any questions you might have about this virtual portfolio, by clicking on the "comments" link right below.

To learn more about the swing trading virtual portfolio (strategy, performance, FAQ, etc.), please click here ...



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Promotions

Free eBook - "My Top Strategies for 2017"

 

 

Here's a free ebook for you to check out! 

Phil has a chapter in a newly-released eBook that we think you’ll enjoy.

In My Top Strategies for 2017, Phil's chapter is Secret Santa’s Inflation Hedges for 2017.

This chapter isn’t about risk or leverage. Phil present a few smart, practical ideas you can use as a hedge against inflation as well as hedging strategies designed to assist you in staying ahead of the markets.

Some other great content in this free eBook includes:

 

·       How 2017 Will Affect Oil, the US Dollar and the European Union

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All About Trends

Mid-Day Update

Reminder: Harlan is available to chat with Members, comments are found below each post.

Click here for the full report.




To learn more, sign up for David's free newsletter and receive the free report from All About Trends - "How To Outperform 90% Of Wall Street With Just $500 A Week." Tell David PSW sent you. - Ilene...

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About Phil:

Philip R. Davis is a founder Phil's Stock World, a stock and options trading site that teaches the art of options trading to newcomers and devises advanced strategies for expert traders...

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About Ilene:

Ilene is editor and affiliate program coordinator for PSW. She manages the site market shadows, archives, more. Contact Ilene to learn about our affiliate and content sharing programs.

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