New gene editing method shows promising results for correcting muscular dystrophy


UT Southwestern Medical Center researchers successfully used a new gene editing method to correct the mutation that leads to Duchenne muscular dystrophy (DMD) in a mouse model of the condition.

Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in DNA, allowing the body’s DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the “defect” in a gene rather than just transiently adding a “functional” one, said Dr. Eric Olson, Director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern and Chairman of Molecular Biology.

Using CRISPR/Cas9, the Hamon Center team was able to correct the genetic defect in the of DMD and prevent the development of features of the disease in boys, which causes and degeneration, often along with breathing and heart complications.

“Our findings show that CRISPR/Cas9 can correct the genetic mutation that leads to DMD, at least in mice,” said Dr. Eric Olson, holder of the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research. “Even in mice with only a subset of corrected cells, we saw widespread and progressive improvement of the condition over time, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle.”

He also pointed out “this is very important for possible clinical application of this approach in the future. Skeletal muscle is the largest tissue in the human body and current gene therapy methods are only able to affect a portion of the muscle. If the corrected tissue can replace the diseased muscle, patients may get greater clinical benefit.”

Although the genetic cause of DMD has been known for nearly 30 years, there are no treatments that can cure the condition. Duchenne muscular dystrophy breaks down muscle fibers and replaces them with fibrous and/or fatty tissue causing the muscle to gradually weaken.

DMD affects an estimated 1 in 3,600–6,000 male births in the United States, according to the Centers for Disease Control (CDC). Left untreated, those with DMD eventually require use of a wheelchair between age 8 and 11, and have a life expectancy of 25 years. Initial symptoms include difficulty running and jumping, and delays in speech development. DMD can be detected through high levels of a protein called creatine kinase as it leaks into the blood stream, and is confirmed by genetic testing.

Genome editing through the CRISPR/Cas9 system is not currently feasible in humans. However, it may be possible, through advancements in technology, to use this technique to develop therapies for DMD in the future, Dr. Olson said.

“At the moment, we still need to overcome technical challenges, in particular to find better ways to deliver CRISPR/Cas9 to the target tissue and to scale up,” Dr. Olson said. “But in the future we might be able to use this technique therapeutically, for example to directly target and correct the mutation in and .”

Added Chengzu Long, a graduate student in the Olson lab: “We are working on a more clinically feasible method to correct mutations in adult tissues, and have already made some progress.”

The research, published online in the journal Science, is the inaugural paper from UT Southwestern’s newly established Hamon Center for Regenerative Science and Medicine, made possible earlier this year by a $10 million endowment gift from the Hamon Charitable Foundation. The Center’s goal is to understand the basic mechanisms for tissue and organ formation, and then to use that knowledge to regenerate, repair, and replace tissues damaged by aging and injury.

Degenerative diseases of the heart, brain, and other tissues represent the largest cause of death and disability in the world, affecting virtually everyone over the age of 40 and accounting for the lion’s share of health care costs. Regenerative medicine represents a new frontier in science, which seeks to understand the mechanistic basis of tissue aging, repair, and regeneration and to leverage this knowledge to improve human health.

Scientists report genetic abnormalities in birds, insects, plants near Fukushima


Fukushima’s nuclear disaster has caused genetic damage, a decline in the population and other changes to non-human organisms from plants to butterflies to birds in the area, US and Japanese scientists say.

Barn swallow (image from wikipedia.org by<br /><br />
Malene Thyssen)

In a series of articles published in the latest of US science magazine Journal of Heredity, researches revealed the widespread impact of the March 2011 Fukushima nuclear disaster on biological organisms in the region.

A growing body of empirical results from studies of birds, monkeys, butterflies, and other insects suggests that some species have been significantly impacted by the radioactive releases related to the Fukushima disaster,” stated Dr. Timothy Mousseau, of the University of South Carolina, lead author of one of the studies.

Scientists of all the studies agreed that chronic low-dose exposure to ionizing radiation leads to genetic damage and increased mutation rates in reproductive and non-reproductive cells.

In one study, Mousseau compared effects on non-human organisms of the Fukushima catastrophe with the 1986 nuclear disaster in Chernobyl, Ukraine.

Barn swallows with abnormal white spots on their plumage were found near the Chernobyl plant after the disaster while similarly plumaged swallows in Fukushima were also reported in the wake of the 2011 crisis, the researcher said.

Barn swallows with aberrant white feathers were first detected in Fukushima in 2012 and were observed in increasing frequencies in 2013 and 2014. Although such partial albinos are believed to have reduced probabilities of survival, there are sufficient data to suggest that this character can be inherited and may at least in part result from a mutation(s) in the germline, based on parent–offspring resemblance,” the study said.

 Workers prepare frozen pipes for the construction of an ice wall at the tsunami-crippled Tokyo Electric Power Co.'s Fukushima Daiichi Nuclear Power Plant in Okuma, Fukushima Prefecture (AFP Photo / Pool / Kimimasa Mayama)

Workers prepare frozen pipes for the construction of an ice wall at the tsunami-crippled Tokyo Electric Power Co.’s Fukushima Daiichi Nuclear Power Plant in Okuma, Fukushima Prefecture (AFP Photo / Pool / Kimimasa Mayama)

Mousseau said that researchers were monitoring these species for signs of population decline due to abnormalities in mitochondrial DNA, since the same problem was reported in Chernobyl.

Genetic mutations have been previously found in three generations of pale grass blue butterflies living near the crippled Fukushima plant. Researchers found size reduction, slowed growth, high mortality and morphological abnormality both at the Fukushima site and among laboratory-bred butterflies with parents collected from the contaminated site.

Non-contaminated larvae fed leaves from contaminated host plants collected near the reactor showed high rates of abnormality and mortality,” explained Dr. Joji Otaki of the University of the Ryukyus in Okinawa, Japan.

Researchers also suggested that there may be possible evolution of radiation resistance in Fukushima butterflies as well.

Another study showed the impact of radiation on rice. Healthy seedlings were exposed to low-level gamma radiation at a contaminated site in Fukushima Prefecture. After three days, such effects as activation of genes involved in self-defense, ranging from DNA replication and repair to stress responses to cell death were observed.

Mousseau called for continuing studies at Chernobyl which could predict likely effects in the future at the Fukushima site. Following the Chernobyl nuclear power plant meltdown scientists were able to obtain biological samples for research after extensive delays which resulted in limited information on the impacts. At Fukushima scientists began collecting information only a few months after the catastrophe, which enabled them to reveal the serious effects on non-human organisms.

Detailed analyses of genetic impacts to natural populations could provide the information needed to predict recovery times for wild communities at Fukushima as well as any sites of future nuclear accidents,” Mousseau said. “There is an urgent need for greater investment in basic scientific research of the wild animals and plants of Fukushima.

The findings raise fears over the long-term effects of radiation on people who faced exposure in the days and weeks following the disaster.

Fukushima studies are beginning to reveal the severe legacy of radiation leaks.


A range of studies on the impact of the Fukushima disaster have revealed the major impact even low-dose exposure to ionising radiation can have on animals and plants.

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Severe genetic mutations found in pale grass blue butterflies (Zizeeria maha) found in 2012 near the Fukushima disaster, with so-called eclosion failure (left) in which the butterfly can’t fight its way out of its cocoon, and bent wings (left).

A series of research that began just a few months after the meltdown of the Fukushima Daiichi power plant in Japan in 2011 has been published in the Journal of Heredity, and it’s revealing some serious fallout from the radiation leak.

The studies looked at a range of non-human organisms and show that genetic damage, mutations and populations declines have all resulted from the disaster.

“A growing body of empirical results from studies of birds, monkeys, butterflies, and other insects suggests that some species have been significantly impacted by the radioactive releases related to the Fukushima disaster,” Timothy Mousseau from the University of South Carolina in the US, who led one of the studies, explained in a press release.

One thing that all of the published studies have in common is that they hypothesise that low-dose exposure to ionising radiation, like the kind that followed Fukushima, causes genetic damage and increases mutation rates in both reproductive and non-reproductive cells.

A study on the common pale grass blue butterfly, for example, found size reduction, slowed growth, high mortality and morphological abnormality both in butterflies from contaminated sites and their offspring. Some of their results also suggested that Fukushima butterflies might even have evolved radiation resistance.

Another paper showed that rice seedlings in a contaminated site had activated self-defence genes – which can be involved in DNA replication and repair, as well as cell death – in response to the low-level gamma radiation.

A review in the series looked at species from both Chernobyl and Fukushima and showed significant consequences of radiation, such as major popular declines in birds, butterflies and cicadas, as well as morphological changes in the feathers of birds.

While the studies can’t necessarily undo the damage, they most importantly act as a baseline that can be used in future research on the effects of radiation leaks in the environment – something that is needed to help protect the environment from future damage.

“Detailed analyses of genetic impacts to natural populations could provide the information needed to predict recovery times for wild communities at Fukushima as well as any sites of future nuclear accidents,” Mousseau said in a press release. “There is an urgent need for greater investment in basic scientific research of the wild animals and plants of Fukushima.”

Complete response of sunitinib therapy for renal cell cancer recurrence in the native kidney after renal transplantation: a case report.


No case report has yet shown that sunitinib therapy for the postoperative recurrence of renal cancer in a native kidney after renal transplantation can achieve complete response (CR).Case presentationA tumor was detected in the right native kidney of a 35-year-old Japanese male 10 years after renal transplantation. A tumor thrombus that reached the atrium was detected, which suggested cT3cN0M0.

Because of the risk of perioperative complications, preoperative therapy with sunitinib was selected and 8 courses were administered. The size of the primary tumor was reduced by 33%, while that of the tumor thrombus was decreased by 39.5%.Right nephrectomy and removal of the tumor thrombus were then performed.

Contrast-enhanced computed tomography (CT) four months after surgery suggested local relapse. Sunitinib was administered for 9 months, which led to complete response (CR).

Conclusions: This study presented the case of sunitinib therapy for renal cancer in the native kidney after renal transplantation.

PLANTS MAY USE NEWLY DISCOVERED MOLECULAR LANGUAGE TO COMMUNICATE.


A Virginia Tech scientist has discovered a potentially new form of plant communication, one that allows them to share an extraordinary amount of genetic information with one another.

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The finding by Jim Westwood, a professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences, throws open the door to a new arena of science that explores how plants communicate with each other on a molecular level. It also gives scientists new insight into ways to fight parasitic weeds that wreak havoc on food crops in some of the poorest parts of the world.

His findings were published on Aug. 15 in the journal Science.

“The discovery of this novel form of inter-organism communication shows that this is happening a lot more than any one has previously realized,” said Westwood, who is an affiliated researcher with the Fralin Life Science Institute. “Now that we have found that they are sharing all this information, the next question is, ‘What exactly are they telling each other?’.”

Westwood examined the relationship between a parasitic plant, dodder, and two host plants, Arabidopsis and tomatoes. In order to suck the moisture and nutrients out of the host plants, dodder uses an appendage called a haustorium to penetrate the plant. Westwood has previously broken new ground when he found that during this parasitic interaction, there is a transport of RNA between the two species. RNA translates information passed down from DNA, which is an organism’s blueprint.

His new work expands this scope of this exchange and examines the mRNA, or messenger RNA, which sends messages within cells telling them which actions to take, such as which proteins to code. It was thought that mRNA was very fragile and short-lived, so transferring it between species was unimaginable.

But Westwood found that during this parasitic relationship, thousands upon thousands of mRNA molecules were being exchanged between both plants, creating this open dialogue between the species that allows them to freely communicate.

Through this exchange, the parasitic plants may be dictating what the host plant should do, such as lowering its defenses so that the parasitic plant can more easily attack it. Westwood’s next project is aimed at finding out exactly what the mRNA are saying.

Using this newfound information, scientists can now examine if other organisms such a bacteria and fungi also exchange information in a similar fashion. His finding could also help solve issues of food scarcity.

“Parasitic plants such as witchweed and broomrape are serious problems for legumes and other crops that help feed some of the poorest regions in Africa and elsewhere,” said Julie Scholes, a professor at the University of Sheffield, U.K., who is familiar with Westwood’s work but was not part of this project. “In addition to shedding new light on host-parasite communication, Westwood’s findings have exciting implications for the design of novel control strategies based on disrupting the mRNA information that the parasite uses to reprogram the host.”

Westwood said that while his finding is fascinating, how this is applied will be equally as interesting.

“The beauty of this discovery is that this mRNA could be the Achilles hill for parasites,” Westwood said. “This is all really exciting because there are so many potential implications surrounding this new information.”

VACCINES HAVE MADE WORLD A HEALTHIER PLACE TO LIVE.


As you will see below, vaccines have become the miracle that the world needed to protect itself against these deadly diseases. Pre-vaccine era estimated annual morbidity in the US vs the most recent reports of disease cases in the US.

This inforgraphic designed by Leon Farrant is based on Centers for Disease Control & Prevention data collected in 2007 on past incidence of these diseases. This was published here, in the Journal of the American Medical Association.

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First Date And Job Interview Tips: How The Science Of Body Language Can Help You In Awkward Moments


When do you experience your most awkward moments in life? Some people would say on a first date, others on a job interview. (Many would say, “um, both are terrible.”) Too often self-consciousness and uncertainty ends in sheer embarrassment as you hear your too-loud laugh echoing off the conference room walls or when you accidentally expose yourself while reaching for the coffee cup you knocked to the floor. Dates and interviews don’t need to be so weird. Really.

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It’s simply a matter of applied science, or in this case, applied social science, and it begins and ends with “impression management,” which is all about making a very conscious attempt to control your behavior — mostly by using good old-fashioned body language — in order to make exactly the kind of impression you want to make. One caveat: There is a flip side to the impression management coin, and it is important to remember because this is where many people often fail.  Along with controling the details of self-presentation, you might also become aware of your response to the other person. When your date or potential boss does the unexpected — or simply the expected — a weird reaction on your part could be more telling than all the pro-active steps you’ve taken to create a positive first impression. Keeping that in mind…

Tip #1

The oldest rule in the book is true, so stop fighting it and use it to your advantage instead. Appearance is the first nonverbal message received and strongly influences how we judge one another. This simple truth might inspire some people to sprint in the direction of a plastic surgeon’s office, but a lot can be achieved simply through how you dress.

The most significant thing your clothes tell others is whether you fit in or, more importantly, whether you fit with them. Sometimes it means you take care to own a few but clearly expensive outfits; other times it means you spend some time digging through bins at Goodwill to find the perfect quaint style. Ever meet a person who makes a great first-impression, yet after knowing him or her you one day realize they’re actually not half as attractive as you originally thought? Clothes and attitude, baby. Clothes and attitude.

Tip #2

Act like you’re happy to be there. Entering an interview, try to calmly look at each person in the room and then repeat as necessary. While you’re at it, why not smile slightly, too. Though you know you’re nervous and about to pee in your pants, the other people in the room simply think you’re stuck up or ignoring them when you nervously stare straight ahead and don’t acknowledge their presence. Trying to appear happy to be there while on a date, your tendency might be to act overly (falsely) happy, but it’s more about controling your nervous gestures, such as glancing away, and simply maintaining your cool… and your eye contact. Pretty simple, right?

Remember this: Nonverbal communication trumps verbal communication whenever the two do not match up. So, whether you’re on a date or a job interview, you need to concentrate on aligning your nonverbal behavior with your desired message, whether that be “Take me home, now!” or “Gimme the job!”

Tip #3

Social psychologist Amy Cuddy suggests, whether you’re about to enter a job interview or go on a first date, stand in front of a mirror, put your hands on your hips, tilt your chin up, and make yourself as tall as you can be. “Power posing,” as Cuddy and others refer to it, even for just two minutes, increases testosterone levels (associated with dominance) and decreases cortisol (associated with stress). Together, this shift in hormones can help you feel more in control in the two situations most likely to make you feel out of control, and so encourages you to act more naturally and with greater confidence. You feel more able to be you.

Tip #4

In a study conducted at Indiana University, American participants watched videos of speed-dating events in Germany and then guessed which daters were sexually attracted to each other. Based on posture, tone of voice, and eye contact, all participants correctly judged men’s interest and incorrectly judged women’s interest. What tripped them up? They judged women who were “just being sociable” as sexually interested. Let that be a lesson to you.

So what are the true signs of sexual interest? Men tend to draw attention to themselves by laughing loud and at times spreading their arms wide. Men and women both smile more broadly. Women’s voices tend to sound sing-songy, while men’s voices drop an octave. When flirting, many people mimic the other person’s stance and movements. The final sign of interest? Making physical contact, as when you briefly touch the other person’s hand or arm. These are the signs understood as flirtation. If you’re naturally flirty, try to avoid displaying these behaviors while in a job interview or while on a date with someone you’re not quite sure of. And if you more naturally tend toward an Asperger’s-like demeanor, reverse engineer your behavior to match the above signals whenever you want to flirt.

Tip #5

Warmth and competence account for about 80 percent of how all of us, including potential bosses and first dates, evaluate other people. Unfortunately, people often see warmth and competence as inversely related so you must get the balance right in any given situation. On a date, well, you might want to aim for a more approachable behavior. Signals of warmth include: appropriate self-disclosure, use of humor, natural smiles, leaning toward someone, and getting physically closer.

In any business context and especially a job interview, Cuddy says it’s important you don’t come across as really really nice, because people might not think you’re the bulb with the highest wattage. How do you do this? Assume a posture that is expansive, open, and takes up more as opposed to less space.  Such a posture signals power and dominance and will counter-act any possibility of over niceness. What you want to avoid is what Cuddy refers to as a ‘contractive’ posture — when your limbs touch your torso as if protecting your vital organs and when you take up minimal space by crossing your legs or not sitting up to your tallest height. When animals are prey they make themselves as small as possible, Cuddy warns.

The Big Bad Bonus Dating Tip

Trust the truth of who you are and what you want.

In a 2006 study, 39 male students were shown10 pairs of pictures and asked to pick their favorite. Yet each pair contained the same combination of one picture of an infant and another of an adult. The researchers gauged the men’s interest in babies by how many times they preferred the photo of an infant over an adult. Next, 29 female students at another university were asked to look at each man’s photo and judge how interested he was in children. Oddly, the women’s perceptions matched the men’s expressed interest in infants (as evidenced by the choices they made among the paired photographs).

Now here comes the interesting part: The women were then asked which men they would be interested in as a “mate.” The women who previously said they wanted a long-term relationship found the men who were interested in children more attractive, while women who said they wanted a short-term relationship found the men less interested in children more attractive. Simply by looking at a man, a woman understands if he is potential “father material.”

Gold to kill brain cancer tumour cells


It is a golden idea that could revolutionize cancer treatment.

A “Trojan horse” treatment for an aggressive form of brain cancer, which involves using tiny nanoparticles of gold to kill tumour cells has been successfully tested by scientists in UK.

The ground-breaking technique could eventually be used to treat glioblastoma multiforme – the commonest and most aggressive brain tumour in adults and notoriously difficult to treat.

Most patients die within a few months of diagnosis and just six in every 100 patients with the condition are alive after five years.

The research involved engineering nanostructures containing both gold and cisplatin, a conventional chemotherapy drug. These were released into tumour cells that had been taken from glioblastoma patients and grown in the lab.

Once inside, these “nanospheres” were exposed to radiotherapy. This caused the gold to release electrons which damaged the cancer cell’s DNA and its overall structure, thereby enhancing the impact of the chemotherapy drug.

The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

Gold is a benign material which in itself poses no threat to the patient, and the size and shape of the particles can be controlled very accurately. When exposed to radiotherapy, the particles emit a type of low energy electron, known as Auger electrons, capable of damaging the diseased cell’s DNA and other intracellular molecules. This low energy emission means that they only have an impact at short range, so they do not cause any serious damage to healthy cells that are nearby.

In the new study, the researchers first wrapped gold nanoparticles inside a positively charged polymer, polyethylenimine. This interacted with proteins on the cell surface called proteoglycans which led to the nanoparticles being ingested by the cell. Once there, it was possible to excite it using standard radiotherapy, which many GBM patients undergo as a matter of course. This released the electrons to attack the cell DNA. While gold nanospheres, without any accompanying drug, were found to cause significant cell damage, treatment-resistant cell populations did eventually recover several days after the radiotherapy. As a result, the researchers then engineered a second nanostructure which was suffused with cisplatin. The chemotherapeutic effect of cisplatin combined with the radio sensitizing effect of gold nanoparticles resulted in enhanced synergy enabling a more effective cellular damage.

Subsequent tests revealed that the treatment had reduced the visible cell population by a factor of 100 thousand, compared with an untreated cell culture, within the space of just 20 days.

No population renewal was detected. The researchers believe that similar models could eventually be used to treat other types of challenging cancers.

New vaccine to prevent chikungunya developed


In a breakthrough, scientists have developed a new vaccine candidate to provide protection from the mosquito-borne viral illness chikungunya.

The experimental vaccine elicited neutralising antibodies in all 25 adult volunteers who participated in a recent early-stage clinical trial conducted by researchers at the National Institute of Allergy and Infectious Diseases (NIAID).

The most distinctive symptom of chikungunya infection is severe joint pain accompanied by headache and fever. There are currently no vaccines or specific drug treatments for chikungunya.

In 2010, Vaccine Research Centre (VRC) scientists and colleagues tested this candidate chikungunya vaccine in non-human primates.

All of the immunised animals were protected from infection when later exposed to chikungunya virus.

In the newly reported trial, 23 healthy volunteers received three injections (two other volunteers received two injections) of vaccine at one of three different dosages (10, 20 or 40 microgrammes) over a 20-week span.

Antibody production was measured at multiple time points following each injection.

Investigators detected chikungunya neutralising antibodies in all volunteers following the second injection, with a significant boost of neutralising antibodies seen following the third injection.

Vaccine-induced antibodies persisted in all volunteers, even those who received the lowest dosage, for at least 11 months after the final vaccination, suggesting that the vaccine could provide durable protection against disease.

“The candidate vaccine prompted a robust immunological response in recipients and was very well tolerated,” noted VRC scientist Julie E Ledgerwood, principal investigator of the trial.

“Notably, the levels of neutralising antibody produced in response to the experimental vaccine were comparable to those seen in two patients who had recovered from a chikungunya virus infection acquired elsewhere.

“This observation gives us additional confidence that this vaccine would provide as much protection as natural infection,” Ledgerwood said.

Whereas traditional vaccines are typically made from either killed viruses or from weakened live viruses, the experimental vaccine used in the trial is a different type: a virus-like particle (VLP) vaccine.

VLP vaccines contain the outer shell proteins of a virus without any of the material the virus needs to replicate inside cells.

The finding was published in The Lancet journal.

Using skin whitening products? Some creams may contain toxic mercury


Some people slather and even inject creams containing mercury onto or under their skin to lighten it, putting themselves and others at risk for serious health problems, scientists say.

Researchers say they can now identify these creams and intervene much faster than before.
“In the US, the limit on mercury in products is 1 part per million,” said Gordon Vrdoljak, of the California department of public health (CDPH).

“In some of these creams, we’ve been finding levels as high as 210,000 parts per million — really substantial amounts of mercury. If people are using the product quite regularly, their hands will exude it, it will get in their food, on their countertops, on the sheets their kids sleep on,” said Vrdoljak.

Identifying the toxic products has been a slow process, however. So, Vrdoljak turned to an instrument that uses a technique called total reflection x-ray fluorescence.

He found that the machine can screen product samples for mercury content far more efficiently, and just as accurately, as its well-established but time-consuming counterpart. That means the team can identify the sources of mercury poisoning and help those affected much faster than before.

“Testing one product using the old technique could take days,” Vrdoljak said.

“Using the new instrument, I can run through 20 or 30 samples in a day quite easily. By identifying those products that contain mercury, we can direct people to remove them and clean up their households,” he said.

Although the metal does lighten skin, dark spots and even acne, research has shown that the silvery liquid can cause a number of health problems, including lower cognitive functioning, kidney damage, headaches, fatigue, hand tremors, depression and other symptoms.

As a result, the US and many other countries have set low limits on or have banned mercury in consumer products.

But demand is high among certain populations for these skin-lightening products, researchers said.

The work has led to two product recalls earlier this year, but often, they find the cosmetics are homemade and come in unmarked containers, researchers said.

The research was presented at the National Meeting and Exposition of the American Chemical Society (ACS) in San Francisco.