Investigators at Stanford University have identified a small group of nerve cells in a specific brain region of rats whose signaling activity, or lack of it, explains the vast bulk of differences in risk-taking preferences among the animals.
That activity not only predicts but effectively determines whether an animal decides to take a chance or stick with the safe choice.
The findings expand on noninvasive research conducted previously in humans. “Humans and rats have similar brain structures involved,” said Karl Deisseroth, MD, PhD, professor of bioengineering and of psychiatry and behavioral sciences. “And we found that a drug known to increase risk preference in people had the same effect on the rats. So every indication is that these findings are relevant to humans.
“Risky behavior has its moments where it’s valuable,” he added. “As a species, we wouldn’t have come as far as we have without it.”
But a propensity for high-risk behavior can be damaging, too, said Deisseroth, a practicing psychiatrist. “I’ve seen patients whose aberrantly high-risk-seeking activity resulted in accidents, addictions and social, financial or occupational failures that exposed them to a lot of harm and blame.”
The research is described in a paper to be published online March 23 inNature. Deisseroth is the senior author. The lead author is graduate student Kelly Zalocusky.
By throwing light not only on how individual decisions are made but on why individuals differ in their overall risk-taking profiles, the study could provide a better understanding of some psychiatric conditions and lead to better medications to treat them. And, for that matter, it could help researchers mitigate the effect of drugs that themselves influence risk preferences. For example, a drug called pramipexole, prescribed for Parkinson’s disease and other brain disorders, can cause gambling problems.
Appetite for risk varies
Individuals vary in their appetite for risk, said Deisseroth, the D.H. Chen Professor and a Howard Hughes Medical Institute investigator. Most adult humans are relatively risk-averse. Given a choice between, say, a stable salary or fluctuating freelance income that’s likely to wind up being about the same or even somewhat larger in the long run, individuals will usually pick the salaried option.
That makes evolutionary sense, Deisseroth said. “One can’t always take the long view. In an always-changing world filled with dangers ranging from starvation to predators, even if a riskier option has a higher expected return over time, one can’t always live long enough to take advantage of it,” he said.
However, a minority within each species studied tends to prefer risk. And even largely risk-averse individuals sometimes choose riskier options.
The researchers focused on a complex of brain circuitry known as the reward system that is shared by every living creature from flies to humans. This circuitry’s evolutionary conservation is due to its essential role in guiding individuals’ behavior, and ensuring species’ survival, by inducing pleasurable sensations and boosting motivation in response to the anticipation or realization of behaviors such as eating and mating.
Reward system’s key nerve tract
A core feature of the reward system is a nerve tract projecting from a deep-brain structure called the ventral tegmental area to another structure in the forebrain, the nucleus accumbens. Nerve cells in this tract can secrete a chemical called dopamine that binds to surface receptors residing on some nerve cells in the nucleus accumbens. This, in turn, ignites activity within the cells that harbor dopamine-receptors. The receptors fall mainly into two categories, DR1 and DR2, that are mostly found on different cells.
Drawing on hints from the medical literature — including previous human brain-imaging research by study co-author and associate professor of psychology Brian Knutson, PhD, indicating increased activity in the nucleus accumbens when people were considering taking risks — the researchers zeroed in on activity in DR2-containing nerve cells in the nucleus accumbens during the decision-making process. They used a single, hair-thin optical fiber implanted in the rats’ nucleus accumbens to both monitor electrochemical signals there — a technique called fiber photometry — and precisely duplicate these naturally occurring signals’ timing and magnitude by stimulating cells with light — a technique called optogenetics. Both techniques were pioneered in Deisseroth’s lab.
The scientists targeted DR2 cells in rats that had been trained and fitted for both fiber photometry and optogenetics with a thin, implanted optical fiber that allowed the rats to move freely. The experiments that followed were designed by Zalocusky and her colleagues including Knutson and Deisseroth.
Mmmmm, sugar water
The rats could initiate a session by poking their nose into a hole, at which point two levers would pop out. Pulling one lever, the rats soon learned, resulted in a dependable dose of sugar water, always the same size. Pulling the other lever would yield a much smaller sugar-water dose most of the time, but a much larger one every so often. The system was set up so that either lever would earn a rat the same total payoff, eventually.
Once trained, about two-thirds of the rats proved risk-averse, consistently choosing the steady-paying “salary.” The remaining one-third were risk-seeking “freelance” types. If the researchers tricked the rats by reversing the levers’ payoffs, the rats responded by switching levers, each adhering to its own preferred reward schedule.
Occasionally, though, a rat of either type would check out the neglected option. If a risk-averse rat experimenting in this fashion happened to get lucky and reap a windfall, it would try that lever again; if it received a pittance, it quickly returned to the “salary” lever. The easy-come, easy-go risk-seekers were relatively unfazed by smaller-than-anticipated rewards. Like some people, a risk-seeking rat on a losing streak doesn’t give up so easily.
Altering rats’ risk preferences
Fiber-photometric observation indicated that — during a roughly 1-second period after a rat initiated the trial but before it was allowed to pull one or the other lever — activity in DR-2-containing nerve cells of the nucleus accumbens was significantly elevated in risk-averse, but not risk-seeking, rats. Mimicking this signaling pattern by optogenetically stimulating DR-2 cells with laser-light pulses, the researchers caused risk-seeking rats to become risk-averse. Their gambling penchant returned as soon as the laser pulses were halted. Stimulating the same cells in rats that were already risk-averse produced essentially no change in their behavior.
In contrast, delivering pramipexole (a DR2-stimulating drug that promotes risky behavior in people) directly to the rats’ nucleus accumbens temporarily converted risk-avoider rats into risk-seekers and also reduced the signal’s size in their nucleus accumbens. A DR1-stimulating compound had no such effect.
“It looks as though we have found a brain signal that, in most individuals, corresponds to a memory of a failed risky choice,” said Deisseroth. “It seems to represent the memory of that recent unfavorable outcome, manifested later at just the right time when it can, and does, modify an upcoming decision.”
The signal was highest in risk-averse rats that had been dealt a disappointing outcome on the previous trial, and was weak in risk-seeking rats, unless forced into existence by optogenetic stimulation. This signal could serve as a guide for understanding interpersonal variability in risk-seeking. “It also might be possible to use this animal assay to predict how different drugs can influence human risk-taking,” Zalocusky said.
A diagnosis can floor you, and no one is immune. Almost every family has been touched in some way by cancer. Those who have had a loved one succumb to the disease know what a terrible way it can be to perish. Cancer is the second most common killer in the U.S.
In his 2016 State of the Union address, President Obama announced a “moonshot” plan to cure this pernicious disease. Vice president Joe Biden was tapped to head “mission control.” The National Institutes of Health (NIH) and some private institutions soon began ramping up their efforts. The NIH was one of the few departments to see an increase in funding from Congress for this to the tune of $264 million. A roadmap has also been created, condensing a decade’s worth of research into half that time. In a recent visit to Cuba, the first time a sitting president has been there since 1928, Obama and Cuban President Raoul Castro announced a partnership on tackling communicable diseases including the Zika virus, as well as cancer. Cuba claims to have a vaccine against the lung borne variety. These efforts are heartening. But how close are we to seeing the end of this scourge, one of the top three killers on the planet?
Research oncologists say it is a complex set of conditions, not just one. A single cure may not be possible. But incredible strides have been made. Today, a 10 year remission is possible for melanoma sufferers, the most common cancer among men. This was thought unheard of just five years ago. Rapid breakthroughs have also come to the fore in our understanding of the hereditary roots of the disease. 10 genetic markers so far have been identified. Another advancement has been in immunotherapy—using the body’s own immune system to identify and fight cancer cells. Some cancerous tumors such as with lung or skin cancer are easy targets for immunotherapy.
But challenges remain. Take the case of prostate cancer, where the cells don’t center on one specific site or lesion. Instead, they spread like seeds throughout the gland, making immune system targeting difficult. Instead of a cure, most cancer researchers talk about better remission rates, as there is always the chance that the cancer may return. Since President Nixon’s “War on Cancer” in 1971, we’ve made great progress. 1.7 million deaths have been avoided between 1991 and 2012, according to the American Cancer Society. But many of these are due to the stamping out of smoking, and better screening for breast and prostate cancer. This scourge of humanity is likely to be with us for some time. But better ways of diagnosing and treating it are coming online, and more are about to be discovered. We may not cure cancer anytime soon. But we are making great progress in the fight against it.
“We have indeed reached an inflection point, where the number of discoveries that are being made at such an accelerated pace are saving lives and bringing enormous hope for cancer patients, even those with advanced disease.” -Dr. José Baselga MD, PhD., President of The American Association for Cancer Research.
Ever marveled at your derm’s clear, dewy complexion and wondered how it stays that way year after year? If you ask, they’ll credit their flawless face to always doing two things: washing at night and wearing sunscreen during the day. But don’t be fooled—they have lots of little tricks up their sleeves to ward off acne, tighten pores, smooth wrinkles, erase sun spots, and bring on the radiance. We got 12 dermatologists to reveal the one skin care step that gets top billing in their daily routine.
They circumvent dirt magnets.
“I change my face towel daily. A bathroom towel contains the perfect storm to cultivate bacteria and breakouts—warmth, moisture, and plenty of dead skin.”
—Mark H. Schwartz, MD, NYC plastic surgeon and clinical assistant professor of plastic surgery at Weill Cornell Medical College
“When I wash my face at night I always put my hair back. People often miss cleansing the area right next to the hairline. And I keep my hair off my face when I sleep, because hair acts like a magnet for dirt and pollution. The last thing I want is to roll over in my sleep and have dirt and pollution all over my face.”
—Diane Madfes, MD, board certified dermatologist with Madfes Aesthetic Medical Center in NYC
They swear by retinoids.
“I have been using prescription topical retinoids at night for more than a decade. These vitamin A relatives stimulate collagen production, keeping the skin strong and supple and more resistant to wrinkling. Using the prescription just a few times per week has a significant impact over time. I recommend starting out with an OTC version and adjusting to a prescription once your skin has acclimated.”
—Joshua Zeichner, MD, director of cosmetic & clinical research, assistant professor of dermatology, The Mount Sinai Hospital
They don’t dry off.
“I like to apply my products to very slightly damp skin, so after washing and cleansing, I leave a residual film of water on my face and then apply the products. The packages may say ‘dry skin,’ but I think that extra little bit of moisture allows the products to better glide onto the skin.”
—Seemal R. Desai, MD, FAAD, founder and medical director, Innovative Dermatology PA, Plano, TX
They hydrate like crazy.
“The skin needs moisture to look plump, smooth and vibrant. Moisturizers that contain hyaluronic acid are ‘superhydrators’—the ingredient can carry up to 10 times its weight in water. Also, I drink 8 to 10 glasses of water a day to keep my skin hydrated from the inside out.”
—Felipe Jimenez, PhD, chief scientific officer of ClarityMD
They prioritize oil.
“My assistant’s 89-year-old mother used an olive oil water mixture for cleansing and moisturizing every day and didn’t have a wrinkle or spot on her face. I’ve tried my own mix of olive oil and water, argan oil, and lately I’m on a sea buckthorn oil kick. Oil is a great moisturizer and cleanser; it also takes off mascara in seconds without removing lashes.”
—Valerie Goldburt, MD, dermatologist with Advanced Dermatology, P.C., Center for Laser and Cosmetic Surgery in NYC, clinical assistant professor at NYU Langone Medical Center
They’re addicted to serums.
“After washing, serums are the first product to touch my face. In the AM, I use one loaded with antioxidants, like Skinceuticals Serum 15 AOX+, which contains vitamin C to fight free radicals. In the PM I use one that contains growth factors or stem cell derivatives, the building blocks of skin that stimulate collagen and elastin formation as well as skin turnover. Then I’m ready to moisturize and apply sunscreen.”
—Chris G. Adigun, MD, board certified dermatologist based in Chapel Hill, NC
They keep a lip product on their nightstand.
“I literally have to put Aquaphor on my lips every morning when I get out of bed. I tend to have very dry lips and also like really matte lipstick, so the Aquaphor provides a hydrating base and prevents dryness and flaking.” (Here’s how to prevent chapped lips.)
—Rebecca Kazin, MD, FAAD, associate director of the Washington Institute of Dermatologic Laser Surgery and faculty at Johns Hopkins department of dermatology
They pay special attention to their eyes.
“The eyes are the first place to show signs of aging and need delicate care, so it’s worth the splurge to have a separate eye cream. I use IS Clinical Eye Complex in the morning because it contains caffeine which helps with depuffing, and ReGenica Overnight Repair at night because it has growth factors that are restorative overnight.”
—Elizabeth Tanzi, MD, founder and director of Capital Laser & Skin Care, and assistant clinical professor, department of dermatology at the George Washington University Medical Center
They carefully calibrate their shower temp.
“I take warm showers. If the temperature is too hot, it strips the skin of its natural oils, leaving it itchy and dry. And I always moisturize within 3 minutes of hopping out of the shower, using a pH balanced moisturizer, like Sebamed Moisturizing Body Lotion.”
—Marnie B. Nussbaum, MD, FAAD, a clinical instructor of dermatology at Weill Cornell Medical Center
They don’t wait until bedtime to wash up.
“I wash the day off as soon I get home, even if it’s mid-afternoon. And if I have makeup on when I work out (generally a no-no, but sometimes it happens), then I wash it off as soon as I finish—while the sweat is still wet, before my pores get clogged.”
—Chris G. Adigun, MD
They strategically remove makeup.
“My golden rule: Do not rub your eyes! Eyelid skin is the thinnest on the body and most prone to aging, even from aggressive rubbing. To remove eye makeup, I pat Vaseline or Aquaphor onto the whole eye area, let it ‘melt’ my eye makeup for 5 minutes, then gently wipe it off with a cotton pad or soft tissue. You can do this even if you have oily or acne-prone skin because the eye area has no hair follicles or pores to produce oil and become clogged.”
—S. Manjula Jegasothy MD, founder, Miami Skin Institute, clinical associate professor of dermatology, University of Miami Miller School of Medicine
They don’t just focus on their face.
“Since stopping an oral contraceptive, I’ve been dealing with adult acne on my back and I’ve been finding salicylic acid and Aczone, a prescription acne gel, to be most helpful. They don’t irritate my skin or bleach my shirts. I use a salicylic acid wash (I like Neutrogena’s Oil-Free Acne Wash Pink Grapefruit Cleanser or Biore’s Acne Clearing Scrub) every time I shower, and rub on Aczone every morning and night.”
—Hadley King, MD, dermatologist at SKINNEY Medspa in NYC
“Many people show their age on their neck, because they’ve neglected it for so many years. I apply the same serums, moisturizers, and sunscreens that I use on my face to my neck as well.”
—Chris G. Adigun, MD
Researchers from Temple University have used the CRISPR/Cas9 gene editing tool to clear out the entire HIV-1 genome from a patient’s infected immune cells. It’s a remarkable achievement that could have profound implications for the treatment of AIDS and other retroviruses.
When we think about CRISPR/Cas9 we tend to think of it as a tool to eliminate heritable genetic diseases, or as a way to introduce new genes altogether. But as this new research shows, it also holds great promise as a means to eliminate viruses that have planted their nefarious genetic codes within host cells. This latest achievement now appears in Nature Scientific Reports.
Retroviruses, unlike regular run-of-the-mill viruses, insert copies of their genomes into host cells in order to replicate. Antiretroviral drugs have proven effective at controlling HIV after infection, but patients who stop taking these drugs suffer a quick relapse. Once treatment stops, the HIV reasserts itself, weakening the immune system, thus triggering the onset of acquired immune deficiency syndrome, or AIDS.
Geneticist Kamel Khalili and colleagues from Temple University extracted infected T-cells from a patient. The team’s modified version of CRISPR/Cas9—which specifically targets HIV-1 DNA—did the rest. First, guide RNA methodically made its way across the entire T-cell genome searching for signs of the viral components. Once it recognized a match, a nuclease enzyme ripped out out the offending strands from the T-cell DNA. Then the cell’s built-in DNA repair machinery patched up the loose ends.
Not only did this remove the viral DNA, it did so permanently. What’s more, because this microscopic genetic system remained within the cell, it staved off further infections when particles of HIV-1 tried to sneak their way back in from unedited cells.
The study was performed on T-cells in a petri dish, but the technique successfully lowered the viral load in the patient’s extracted cells. This strongly suggests it could be used as a treatment. However, it could be years before we see that happen. Still, the researchers ruled out off-target effects (i.e. unanticipated side-effects of gene-editing) and potential toxicity. They also demonstrated that the HIV-1-eradicated cells were growing and functioning normally.
These findings “demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4 T-cells and, by introducing mutations into the viral genome, permanently inactivating its replication,” Khalili said in a statement. “Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects.”
This technique for snipping out alien DNA could have implications for related research, including treatments for retroviruses that cause cancer and leukemia, and the suite of retroviruses currently affecting companion and farm animals. As noted by Excision BioTherapeutics’ CEO and President Thomas Malcolm, “These exciting results also reflect our ability to select viral gene targets for safe eradication of any viral genome in our current pipeline of gene editing therapeutics.”
And Malcolm has good reason to be excited: his company holds exclusive rights to commercialize this technology.
In times gone by, humans were more in tune with the environment they lived in. Today, we have little connection to nature and the planet. The ancient wisdom that was often passed down through story- telling and tradition seems to have been forgotten or lost.
The understanding of the importance of different geometric shapes and patterns found everywhere in nature seems to be amongst the wisdom that has been thrown away. With all the changes that are happening on earth at the moment, some of this information is being revived. Here is some information about how the ancient science of Sacred Geometry can have a positive influence on your life.
The earliest cultures including the Christians, Hindus, Greeks and Egyptians recognized that there were different patterns or geometric shapes that repeated throughout nature. They also worked out that there was a correlation or connection between the various elements found in the earth and the heavens. These connections or common patterns, known as Sacred Geometry, were mirrored- the same patterns appeared on the earth and the in sky -and were believed by these ancient cultures to exist in all parts of the universe.
Ice deposits that formed in craters on opposite sides of the Moon three billion years ago indicate it may have once spun on a different axis.
Volcanic activity in the Moon’s interior billions of years ago may have moved the lunar poles to their present position, according to a team of scientists from the Planetary Science Institute in Tucson, Arizona.
They said their calculations, published in the journal Nature, open the way to better understand how water reached the inner solar system.
Lead author Dr Matthew Siegler said the Moon’s axis had moved about six degrees to the rotation we see today.
“It takes a huge change in the mass of the Moon to do that — something like a giant crater or volcano forming,” Dr Siegler said.
He said the team was able to source the change in rotation to the centre of the Procellarum region — the black part of the face of the moon — which is also the centre of nearly all of the volcanism on the Moon.
“By looking at how much the pole moved, we are able to see how this region, which is about 30 per cent of the Moon, and the interior of the Moon evolved,” Dr Siegler said.
Because the Procellarum region was most geologically active early in the Moon’s history, Dr Siegler said it was likely the change in spin axis, known as polar wander, occurred billions of years ago.
Hydrogen deposits evidence of ‘palaeopoles’
The team used modelling to determine what changes in density needed to happen in the Moon’s interior to cause a six-degree movement in the satellite’s orientation.
While analysing lunar hydrogen data from the Moon from almost a decade ago, Dr Siegler’s team noticed that each lunar pole had a hydrogen deposit that was slightly displaced from the true north and south poles.
These hydrogen deposits were directly opposite each other, so that a line drawn from one to the other would pass through the centre of the Moon — and were located equal distances from their respective poles, but in opposite directions.
This suggested these deposits were evidence of “paleopoles” and that the Moon’s spin axis had shifted to its current alignment.
A window on the solar system’s water
Dr Siegler said because the hydrogen was most concentrated in the Moon’s extreme cold regions, it was believed to be water.
“It is really cold in the shadowed craters near the lunar poles, most areas never get above minus 170 degrees Cesius,” Dr Siegler said.
“At these temperatures water ice acts like any other rock — it doesn’t melt or evaporate — so it can stick around forever.
“The ice we are observing, or at least most of it, had to have arrived before the spin axis changed. That likely happened around three billion years ago.
“That means that the moon can provide a record on how water reached the inner solar system, which is generally accepted to have started dry.”
He said future missions sampling the ice might be able to determine whether the water came from comets and asteroids, or from volcanoes on the moon itself.
NASA already had plans for a lunar rover mission in the 2020s that would drill for ice to one-metre depth, however bringing ice samples back was still in the distance.
“The hope is always that new findings like this might influence NASA’s plans,” Dr Siegler said.
Forty-nine years ago Lewis Washkansky received the first heart transplant in Cape Town, South Africa. Since then there have been thousands of transplants done around the world.
However, getting a viable heart is tricky business, and science is trying to increase the odds for those who need a transplant.
The main problem with heart transplants arise from compatibility. A body could reject a whole human heart. part of it for transplantation?
In a first, scientists from Massachusetts General Hospital’s Center for Regenerative Medicine and Harvard Medical School have created a functional heart through bio-engineering.
In the study, the scientists took 73 human hearts that were unsuitable for transplantation and decellularized them, stripping them of the donors’ cells. This prevents a host from rejecting the heart (since there are no foreign cells). What remains is a matrix, or scaffold.
The researchers then reprogrammed the hosts’ skin cells into induced pluripotent stem cells (iPSCs). These special cells are able to become almost any type of cell. In this case, they were reprogrammed to become heart cells and, bathing them in a nutrient solution, the researchers found that the cells were able to grow on the scaffold.
After two weeks of bathing in this solution, the scientists found that the cells had changed into “immature cardiac tissue.” They stimulated it electrically, and it actually started to beat.
“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial patch that could replace cardiac tissue damaged due a heart attack or heart failure,” said Jacques Guyette, of the Center for Regenerative Medicine and lead author of the report.
Though regenerating a whole heart is a long way off, this could bring new hope to those suffering from cardiac issues. Guyette said that current research is looking to develop patches for people with damaged cardiac tissue