Is that Ginkgo biloba supplement really what you think it is? DNA barcoding used to check authenticity of popular herbal supplements

Study: Authentication of Ginkgo biloba herbal dietary supplements using DNA barcoding  by Dr. Damon Little of The New York Botanical Garden

Dr. Damon Little, Associate Curator of Bioinformatics in the Cullman Program for Molecular Systematics at The New York Botanical Garden, has just published a new study in the journal Genome investigating the use of DNA barcoding to test the authenticity of Ginkgo biloba (G. biloba), an herbal dietary supplement sold to consumers that is supposed to boost cognitive capacity. Unfortunately, herbal supplements on the market are subject to mislabelling, and therefore consumers may not be getting the products and benefits they believe they are getting.

Dr. Little’s research is part of a larger effort to evaluate many of the popular herbal supplements on the retail market. He explains two potential dangers of mislabelled supplements:  (1) some adulterants are toxic (alone or in combination with other supplements/drugs); and (2) consumers may not receive the health benefit they seek from mislabelled supplements, potentially worsening their health.

It seems herbal products can be mislabelled either because the supplier incorrectly identified the plant materials (some grow their own materials; some contract with growers; some buy raw materials in bulk; and some buy processed materials in bulk) or because another (usually less expensive) material was substituted.

Although it is difficult to determine how or why a supplement is mislabelled, the process developed with this new research can help to estimate the frequency of mislabelled supplements on the market. It also provides a validated method that can be used by supplement manufacturers for better quality control.

Dr. Little has designed a novel DNA mini-barcode assay that can validate authenticity of G. biloba in herbal dietary supplements.

“I found that 83.8% of ginkgo supplements certainly contained ginkgo. In comparison, previous work has shown that 75% of black cohosh (Actaea racemosa) and 85% of saw palmetto (Serenoa repens) supplements contained the correct species,” says Dr. Little. “For the supplements in which I found no evidence of ginkgo, I cannot be sure if that is because the DNA was destroyed (for example by drying at very high temperatures) or if the samples simply do not contain any ginkgo.”

In any case, it is hoped that this assay will be used by supplement manufacturers to ensure their supplements contain the expected ingredients.

Dr. Little intends to continue this line of research with a focus on other popular herbal supplements.

“Authentication of Ginkgo biloba herbal dietary supplements using DNA barcoding” was published online today in the journal Genome. 
Source: journal Genome

Harvard Study Unveils What Meditation Literally Does To The Brain

Numerous studies have indicated the many physiological benefits of meditation, and the latest one comes from Harvard University.

An eight week study conducted by Harvard researchers at Massachusetts General Hospital (MGH) determined that meditation literally rebuilds the brains grey matter in just eight weeks. It’s the very first study to document that meditation produces changes over time in the brain’s grey matter. (1)

“Although the practice of meditation is associated with a sense of peacefulness and physical relaxation, practitioners have long claimed that meditation also provides cognitive and psychological benefits that persist throughout the day. This study demonstrates that changes in brain structure may underlie some of these reported improvements and that people are not just feeling better because they are spending time relaxing.” – (1) Sara Lazar of the MGH Psychiatric Neuroimaging Research Program and a Harvard Medical School Instructor in Psychology

The study involved taking magnetic resonance images (MRI) of the brain’s of 16 study participants two weeks prior to participating in the study. MRI images of the participants were also taken after the study was completed.

“The analysis of MR images, which focused on areas where meditation-associated differences were seen in earlier studies, found increased grey-matter density in the hippocampus, known to be important for learning and memory, and in structures associated with self-awareness, compassion and introspection.” (1)

For the study, participants engaged in meditation practices every day for approximately 30 minutes. These practices included focusing on audio recordings for guided meditation, non-judgmental awareness of sensations, feelings and state of mind.

“It is fascinating to see the brain’s plasticity and that, by practicing meditation, we can play an active role in changing the brain and can increase our well-being and quality of life. Other studies in different patient populations have shown that meditation can make significant improvements in a variety of symptoms, and we are now investigating the underlying mechanisms in the brain that facilitate this change.” – (1) Britta Holzel, first author of the paper and a research fellow at MGH and Giessen University in Germany

How To Meditate

A common misconception about meditation is that you have to sit a certain way or do something in particular to achieve the various benefits that it can provide. All you have to do is place yourself in a position that is most comfortable to you. It could be sitting cross legged, lying down in a bed, sitting on a couch etc, it’s your choice.

Another common misconception about meditation is that you have to “try” to empty your mind. One important factor I enjoyed reading from the study mentioned above is that participants were engaged in “non-judgmental awareness of sensations, feelings and state of mind.”  When meditating, you shouldn’t try to “empty” your mind. Instead, try to let your thoughts, feelings and whatever emotions you are feeling at the time flow. Don’t judge them, just let them come and go and be at peace with it.

I also believe that meditation is a state of being/mind more than anything else. I feel that one does not have to sit down for half an hour and “meditate” so to speak in order to reap the benefits of it, or to be engaged in the practice itself.  One can be engaged in meditation while they are on a walk, for example, or the time they have right before they sleep. Throughout the day, one can resist judging their thoughts, letting them flow until they are no more, or just be in a constant state of peace and self awareness. Contrary to popular belief, there is more than one way to meditate.

“You will have to understand one of the most fundamental things about meditation: that no technique leads to meditation. The old so-called techniques and the new scientific biofeedback techniques are the same as far as meditation is concerned. Meditation is not a byproduct of any technique. Meditation happens beyond mind. No technique can go beyond mind.” – Osho

Sources:

(1)  http://news.harvard.edu/gazette/story/2011/01/eight-weeks-to-a-better-brain/

http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Grey_matter.html

——–

The United Nations General Assembly today adopted an India-led resolution declaring June 21 as 'International Day of Yoga'. This comes less than three months after Prime Minister Narendra Modi proposed the idea.

It  was introduced by India's Ambassador to the United Nations Asoke Mukerji today and had 175 nations joining as co-sponsors, the highest number ever for any resolution in the 193-member UN Genral Assembly. This is also for the first time that such an initiative has been proposed and implemented by any country in the UN body in less than 90 days.
PM Modi  tweeted he was 'elated' at the UN declaration:
Through the resolution, adopted under the agenda of 'Global Health and Foreign Policy,' the General  Assembly recognised that Yoga "provides a holistic approach to health and well-being" and that wider the dissemination of information about benefits of practising Yoga would be beneficial for the health of the world population.

In introducing the resolution, Mr Mukerji quoted from PM Modi's address to the United Nations General Seembly in which he had asked world leaders to adopt an international Yoga day, saying that by changing lifestyle and creating consciousness, it can help us deal with climate change.

"Yoga embodies unity of mind and body; thought and action; restraint and fulfilment; harmony between man and nature; a holistic approach to health and well being," PM Modi had said.

In suggesting June 21 as the International Day of Yoga, PM Modi had said that the date, one of the two solstices, is the longest day in the Northern Hemisphere and has special significance in many parts of the world.

The UN in its annual calendar has listed nearly 118 international days, years and anniversaries for observance. The main significance of the UN declaring an International Day is to focus the attention of the international community on the topic and to encourage activities among the member states to commemorate the day.
Source:PTI

Snakebite-inundated rural PHCs find new saviour in Ayurveda

 

As govt struggles with anti-venom supply, Ayurvedic tablet miraculously saves woman in Satara PHC, prompting Health Director to make it available across rural Maharashtra

When a 40-year-old female farmhand from rural Malharpeth in Satara was rushed to the area's Primary Healthcare Centre (PHC) around one month ago, her chances of survival had already almost completely diminished — having suffered the bite of an extremely venomous Krait while working in a farm, she had been found unconscious and rushed to medical care, but was given only 20 minutes to live by local medical experts.

In a last ditch attempt to save her life, an oral ayurvedic tablet — 'Pinak' — was administered. Miraculously, the woman began responding within no time, and her life was saved. The exemplary incident sparked the interest of State Health Director Dr Satish Pawar, who is now involved in a bid to make the life-saving tablet available in the around 1,900 PHCs across Maharashtra.

On Wednesday, Pawar confirmed, "We are planning to make this tablet available in all state PHCs in a month or two. After several meetings with Ayurveda experts, we realised that unlike Anti Snake Venom (ASV), which is compulsorily administered by experts or doctors, this tablet can be administered by anybody, like an Auxiliary Nurse Midwife (ANM) — this reduces the usage of and dependency on ASVs, as the tablet is handy and will be soon ubiquitous."

Elaborating on the incident, Malharpeth PHC medical officer Dr Rashmi Kulkarni, told Mirror, "The middle- aged patient was brought to us in an unconscious state and had just about 20 minutes left to live, as the poison had already spread through her system.

Moreover, since ASV injections were unavailable at that time, we were helpless. We had no choice but to call up Ayurveda expert Dr Geeta Pawar who had worked with Sassoon hospital and co-invented Pinak, which we had at the PHC." She continued, "On her instructions, we immediately kept two tablets under the tongue of the patient — to our absolute surprise, the patient started responding 12 minutes later!

We later sent a detailed report to the State Health Director, so that in cases where ASVs — which are often in short supply — are not available, this oral Ayurveda tablet with no side effects can be administered." Kulkarni added that this is the first time an Ayurveda tablet had been known to replace an ASV.

State Deputy Director of Health Services, Dr Pandurang Pawar, said, "There are several remote areas — including the like of Ambegaon, Khed, Junnar, Velha, Nandurbar, Gadchiroli, etc. — where snakebites are still frequently reported, and deaths due to delays in reaching hospital are common. ASVs are also often not available, and quite costly too, with each injection priced at around Rs 4-8,000.

On the other hand, an Ayurveda tablet costs around Rs 400, and is much more easily available." Dr Ashok Nandapurkar, a civil surgeon at Aundh Civil Hospital who also heads 21 rural hospitals in the state, told Mirror, "Shortages of ASVs are rampant — annually, we need almost 10,000 vials of ASVs per annum, and since only one pharma company, Haffkine, manufactures them in association with the State, we regularly experience shortages.

In cases of snakebite — specially from a snake like the Krait — a neuroparalytic attack is imminent, and death is an almost 100 per cent guarantee; but for an Ayurveda tablet that is easy to administer. Treatment modules for snakebites are also something that are often missing — I myself have administered almost 60 ASV injections to one patient who suffered from a snakebite; in contrast, just giving two oral tablets seems very effective.

This will not only save time, but also government expenditure." Pinak co-inventor Dr Geeta Pawar said, "Pinak was invented when I was heading the Ayurveda department at Sassoon General Hospital in 2005. It is a curative not only in cases of snakebite victims, but also works on scorpion and honeybee stings. Since it is purely herbal, there are no recorded adverse effects caused by this tablet.

The clinical trial of this tablet took place at Sassoon in 2007- 2008, when 30 snakebite victims reacted positively to it, and were literally saved by its administration." She added, "The tablet came about when we noticed a severe adverse reaction and worsening of a paralytic attack caused by ASV administration in a patient at a Karad PHC. Thereafter, it was our effort to create a drug that would not only save patients instantly, but would also have no side effects at all."

  We are planning to make this tablet available in all state PHCs in a month or two. It can be administered by anybody, like an ANM.
Source:Pune Mirror

Research Shows This One Plant Can Kill Cancer Cells & Treat Diabetes

Bitter melon is a fruit that grows abundantly in Asia, Africa and the Caribbean. Traditionally it has been used to treat diabetes and other more mild diseases or illnesses.

More recently, bitter melon juice was shown to kill pancreatic cancer cells in vitro and in mice in a study done by the University of Colorado. Considering the results were seen in both in vitro and in vivo tests, the effectiveness of bitter melon juice in treating pancreatic cancer, and potentially other cancers, at a clinical level are promising.[1]

“IHC analyses of MiaPaCa-2 xenografts showed that BMJ(Bitter Melon Juice) also inhibits proliferation, induces apoptosis and activates AMPK (adenosine monophosphate-activated protein kinase) in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness.”

Pancreatic cancer is one of the most difficult cancers to treat due to the fact that it is often discovered late, leaving very little time to treat. Since traditional therapies (chemotherapy, radiation, surgery etc) were not showing promising results and littler advancement was being made, researchers have been looking elsewhere to find treatment.

Interestingly, cannabis, specifically cannabinoids, have been shown to induce apoptic (programmed) death of human pancreatic cancer cells in vitro and stop pancreatic tumor growth in vivo.  Cannabis is perhaps one of the most popular treatments being aggressively pursued right now given its promising results both in labs and anecdotally.

Scientific Evidence

Pancreatic Cancer

Many cancerous tumors have insulin receptors which move glucose to cancer cells helping them to grow and divide. Studies have shown that insulin encourages pancreatic cancer cells to grow in a dose dependant manner, since bitter melon has been shown to help regulate insulin levels, this could help prevent pancreatic cancer over the long-term.

The Colorado University study was led by Dr. Rajesh Agarwal. They examined effects of bitter melon on 4 different lines of pancreatic cancer cells (in vitro) and in mice. For the in vivo studies, mice were injected with pancreatic tumor cells and were randomly divided into one of two groups. One group of mice received water, which was the control group, and the other group was given bitter melon juice for six weeks.

Researchers studied the tumors at the end of the study and results showed that bitter melon juice not only inhibited cancer cell proliferation but also induced apoptosis (programmed cell death). Compared to the control, tumor growth was inhibited by 60% in the treatment group and there were no signs of toxicity or negative effects on the body. With toxicity and negative effects being a huge role in traditional mainstream treatments, this was positive to see.

Diabetes

A number of clinical studies have been conducted to evaluate the efficacy of bitter melon for treating diabetes. Since it is believed that diabetes is a precursor for pancreatic cancer, researchers felt bitter melon could treat diabetes as well after seeing pancreatic cancer results.

In 2011, results of a four week long clinical trial were published in the Journal of Ethnopharmacology that showed modest hypoglycemic effects and significant fructosamine management for those taking 2000mg/day of bitter melon.

As published by the study: “Bitter melon had a modest hypoglycemic effect and significantly reduced fructosamine levels from baseline among patients with type 2 diabetes who received 2,000 mg/day. However, the hypoglycemic effect of bitter melon was less than metformin 1,000 mg/day.”[3]

Another study published in 2008 in the international journal Chemistry and Biology indicated that compounds in bitter melon improved glycemic control, helped cells uptake glucose and improved overall glucose tolerance. This study was done in mice and led to promising advancements in treating diabetes and obesity with bitter melon.

In contrast, a study published in the Journal of Clinical Epidemiology in 2007 did not show significant benefit of the treatment of diabetes by bitter melon but 2 years later in the British Journal of Nutrition it was stated that “more, better-designed and clinical trials are required to confirm the fruit’s role in diabetes treatment.”

Since that 2007 study, more studies have been done to show beneficial effects which perhaps was a result of better design.

Conclusion

When it comes to bitter melon juice, the current research available is showing strong results for specific types of cancer cell destruction, diabetes treatment and potential prevention of pancreatic cancer. Further research and clinical trials would be helpful to better understand how effective this plant can be and in what specific cases. It remains a very promising option that could be explored under the correct supervision.

Other Uses of Bitter Melon

Bitter melon has been used as a traditional medicine for a long time. It has been used to treat: colic, fever, burns, chronic cough, painful menstruation and skin conditions.

How Synthetic Antidepressants Are Harming The Earth

“The amounts of SRIs flooding the Gaian system is disregulating the neuronal networks of the planet, including its individual species, from plants to animals.” - Stephen Harrod Buhner, Plant Intelligence and the Imaginal Realm: Into the Dreaming of Earth

Many are aware of the harm that taking synthetic antidepressants, namely serotonin reuptake inhibitors (SRIs), can cause on a personal level. Few, however, are aware of the harm it can do on a large scale. All life forms on earth, including the very earth itself, are negatively impacted by antidepressants, as they disrupt adaptive processes regulated by serotonin. For example, serotonin is found in plant tissues and, just like it is in humans, it is responsible for various functions crucial to a plant’s quality of life. Because they are not very biodegradable, excretion of SRIs impacts all organisms that use serotonin to function properly, including plants, the animals that eat those plants, and therefore all humans -not just those who directly take antidepressants. When looked at from this perspective, it becomes clear that the decision of whether or not to take SRIs is a much larger one than we thought, as the choice to do so provokes a negative ripple effect on the planet as a whole.

Serotonin In Plants

Serotonin has various functions in plants, including but not limited to reproduction, protection of plant cells, growth, free radical scavenging and the development of root systems -aka a plant’s predominant neural network. 5-HT1a and 2a receptors in the neural networks of plants interact with serotonin similar to the way they do in animals. 5-HT1a receptors, for example, interact with serotonin to create intracellular stability in a plant’s cytoskeleton. In response to environmental stress, 5-HT2a receptors interact with serotonin in the internal cytoskeleton of a plant by inhibiting old patterns of neural networks that are having difficulty adjusting to environmental changes and create new ones that are more adaptable.

How The Use Of Synthetic Antidepressants Harms Plants

Over 50 synthetic serotonin reuptake inhibitors (SRIs) are excreted into the earth, and not a single organism that uses serotonin to function is exempt of paying the harmful repercussions. SRIs are highly active even in trace amounts and are found in virtually all waste water streams in industrial nations, thereby interfering with reproduction, germination and root development in every system on the planet affected by serotonin. All forms of SRIs come equipped with the same destiny of collectively working with one another to deregulate the neuronal networks of the planet. The extent to which any specific type of SRI proves harmful varies, though, with some causing more destruction than others. For example, only 20 uM of Prozac reduces root development from 15-20 per nodal segment to only 4. Worsening the picture is the fact that these SRIs are not very biodegradable. By not very, I mean they take four months to degrade in streams -in the best case scenario. If they manage to sink to the sediment at the bottom of rivers and ponds before degrading, they do not seem to biodegrade at all.

Resources

• Whitlock Kelli. “Casting Prozac upon the waters.” University of Georgia Research Magazine, Summer 2005.
• P. Andrews et. al., “Primum non nocere: An evolutionary analysis of whether antidepressants do more harm than good”
• Ramon Pelagio-Flores et al., “Serotonin, a tryptophan-derived signal conserved in plants and animals, regulates root system architecture probably acting as a neural auxin inhibitor in Arabidopsis thaliana,” 490
• Buhner, Stephen. Plant Intelligence and the Imaginal Realm: Into the Dreaming of Earth. Vermont: Bear & Company, 2014

Yeast are first cells known to cure themselves of prions

Yeast cells can sometimes reverse the protein misfolding and clumping associated with diseases such as Alzheimer's, according to new research from the University of Arizona.
The new finding contradicts the idea that once prion proteins have changed into the shape that aggregates, the change is irreversible.
"It's believed that when these aggregates arise that cells cannot get rid of them," said Tricia Serio, UA professor and head of the department of molecular and cellular biology. "We've shown that's not the case. Cells can clear themselves of these aggregates."
Prions are proteins that change into a shape that triggers their neighbors to change, also. In that new form, the proteins cluster. The aggregates, called amyloids, are associated with diseases including Alzheimer's, Huntington's and Parkinson's.
"The prion protein is kind of like Dr. Jekyll and Mr. Hyde," said Serio, senior author of the paper published today in the open-access journal eLife. "When you get Hyde, all the prion protein that gets made after that is folded in that bad way."
For yeast, having clumps of amyloid is not fatal. Serio and her students exposed amyloid-containing cells of baker's yeast to 104 F (40 C), a temperature that would be a high fever in a human. When exposed to that environment, the cells activated a stress response that changed the clumping proteins back to the no-clumping shape.
The finding suggests artificially inducing stress responses may one day help develop treatments for diseases associated with misfolded prion proteins, Serio said.
"People are trying to develop therapeutics that will artificially induce stress responses," she said. "Our work serves as a proof of principal that it's a fruitful path to follow."

		These yeast cells contain a prion protein that can change shape from a non-clumping form to one that aggregates into clumps called amyloids. Proteins in these cells have the non-clumping...

First author on the paper "Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing" is Serio's former graduate student Courtney Klaips, now at the Max Planck Institute for Biochemistry in Munich. The other authors are Serio's students Megan Hochstrasser, now at the University of California, Berkeley, and Christine Langlois of Brown University. The paper is available here:http://dx.doi.org/10.7554/eLife.04288
National Institute of Health grants R01 GM069802001, F31 AG034754 and F31 GM099383 funded the research.
To accomplish their jobs inside cells, proteins must fold into specific shapes. Cells have quality-control mechanisms that usually keep proteins from misfolding. However, under some environmental stresses, those mechanisms break down and proteins do misfold, sometimes forming amyloids.
Cells respond to environmental stress by making specific proteins, known as heat-shock proteins, which are known to help prevent protein misfolding.
Serio and her students wanted to know whether particular heat-shock proteins could make amyloids revert to the normal shape. To that end, the team studied yeast cells that seemed unable to clear themselves of the amyloid form of the prion protein Sup35.
The researchers were testing one heat-shock protein at a time in an attempt to figure out which particular proteins were needed to clear the amyloids. However, the results weren't making sense, she said.
So she and Klaips decided to stress yeast cells by exposing them to a range of elevated temperatures - as much as 104 F (40 C) - and let the cells do what comes naturally.
As a result, the cells made a battery of heat-shock proteins. The researchers found at one specific stage of the cell's reproductive cycle, the yeast could turn aggregates of Sup35 back into the non-clumping form of the protein.
Yeast cells reproduce by budding. The mother cell partitions off a bit of itself into a much smaller daughter cell, which separates and then grows up.

		fluorescent green chunks in these yeast cells are prion proteins that have assumed the shape that aggregates into clumps called amyloids. The prion proteins in these cells are tagged...

The researchers found in the heat-stressed yeast, just when the daughter was being formed, the mother cell retained most of the heat-shock proteins called chaperones, especially Hsp-104. As a result, the mother had a particularly high concentration of Hsp-104 because little of the protein was shared with the daughter.
The mother cells ended up "curing" themselves of the Sup35 amyloid, although the daughters did not. The degree of curing was correlated with the concentration of Hsp-104 in the cell, and the higher the temperature the more Hsp-104 the cells had.
The Hsp-104 takes the protein in the amyloid and refolds it, Serio said. But she and her colleagues found that just inducing high levels of Hsp-104 in cells by itself does not change the amyloid protein back to the non-clumping form.
"Clearly the heat-shock proteins are collaborating in some way that we don't understand," she said.
Having the amyloid-forming version of the protein is not automatically bad, she said. It may be that shape is good under some environmental conditions, whereas the non-aggregating form is good under others.
Even in humans, amyloid forms of a protein can be helpful, she said. Amyloid proteins are associated with skin pigmentation and with hormone storage.
To clear the amyloid from yeast cells, these experiments triggered cells to make many different heat-shock proteins.
Serio now wants to figure out the minimal system necessary to clear amyloids from a cell. Knowing that may help the development of drug therapies for amyloid-related human diseases, she said.
Source:eLife

Now researchers can see how unfolded proteins move in the cell

CHAMPAIGN, Ill. — When a large protein unfolds in transit through a cell, it slows down and can get stuck in traffic. Using a specialized microscope -- a sort of cellular traffic camera -- University of Illinois chemists now can watch the way the unfolded protein diffuses.

By looking at the dynamics of how the unfolded protein moved in the cell (A), the researchers mapped areas in the cell with different rates of diffusion (B and C).  | Photo courtesy Hannah Gelman

Studying the relationship between protein folding and transport could provide great insight into protein-misfolding diseases such as Alzheimer’s and Huntington’s. Chemistry professor Martin Gruebele and graduate students Minghao Guo and Hannah Gelman published their findings in the journal PLOS ONE.

“We’re looking at the earliest stages of disease, the initial phases of transport of bad proteins,” Gruebele said. In the past, he said, much research on Alzheimer’s and similar disease focused on fibrils, large bundles of misfolded proteins that form in the brain.

“But now, we think the fibrils are just an end product that’s left over when the cell dies, and the actual killing mechanism has to do with migration of the protein to specific places in the cell like the outer membrane,” he said. “Understanding how these mechanisms work at a fundamental level is going to give people more handles on where to look to cure things.”

Researchers have hypothesized that an unfolded protein moves more slowly through the cell, because it would be a big, stringy mess rather than a tightly wrapped package. The Illinois team devised a way to measure how diffusion slows down when a protein unfolds using a fluorescence microscope, then used three-dimensional diffusion models to connect the protein’s unfolding to its motion.

The researchers found that the unfolded protein did indeed slow down, although its speed was not steady.  It sometimes zoomed swiftly to a new location, and sometimes sat idling in one area, like a vehicle in stop-and-go rush-hour traffic. They were able to map out areas of the cell with different rates of diffusion, the cellular version of a speed limit.

The unfolded protein’s slowdown is not only due to size, however. The researchers did additional experiments to prove that the unfolded protein stuck to other molecules in the cell. A class of molecules in the cell called chaperones have the job of binding to parts of proteins that come unfolded, and the researchers found that the unfolded protein interacted more with chaperones than did the properly folded protein. However, when high numbers of proteins unfold, the cell’s systems can get overloaded and the chaperones can’t handle them all.

“Looking at something like this can start to give people a handle on why something that seems relatively harmless in vitro sometimes can have such a large effect in the cell,” Gelman said. “A change that makes a slightly less effective protein in the test tube can turn into a completely fatal mutation in the cell. First, the protein’s role in the cell can no longer be fulfilled. Second, as more and more unfold, they can disrupt the function of the whole cell.”

The researchers think that the unfolded protein is likely to stick to nonchaperone molecules, as well, causing other problems in the cell and disrupting the flow within a cell. They plan to use the specialized microscope to study other proteins and how unfolding affects their diffusion, to see if the properties they observed are universal or if each protein has its own response.

They also hope to use their method to watch how unfolded or misfolded proteins move to the cell’s membrane, where they aggregate and create the problems seen in Alzheimer’s and other diseases.

“There’s a whole cascade of things,” Gruebele said. “If you have a single car accident in the middle of nowhere, it’s really only a problem for the owner. But if you have a single car that stops in the middle of the road on the freeway in Los Angeles, very soon the entire freeway is going to be backed up. What we’re looking at is like the car stopping on the freeway. We’re not worried yet about what happens to the line of cars an hour later – that’s the fibril.”

The National Science Foundation supported this work.

Source:Plos One

People with mental illness more likely to be tested for HIV, Penn Medicine study finds

First study to investigate rate of HIV testing in patients with specific mental illnesses

PHILADELPHIA--People with mental illness are more likely to have been tested for HIV than those without mental illness, according to a new study from a teamof researchers at Penn Medicine and the U.S. Centers for Disease Control and Prevention (CDC) published online this week in AIDS Patient Care and STDs. The researchers also found that the most seriously ill - those with schizophrenia and bipolar disease - had the highest rate of HIV testing.
The study assessed nationally representative data from 21,785 adult respondents from the 2007 National Health Interview Survey (NHIS) and provides an update of prior research using 1999 and 2002 NHIS data. The 2007 version is the most recent cycle of the survey that included information both on mental health diagnoses and HIV testing.
The current Penn-led study adds precision to earlier research by reporting on HIV-testing rates according to specific mental health diagnoses; previous studies did not differentiate persons with, for example, depression, bipolar disorder, and schizophrenia spectrum disorder.
The researchers found that 15 percent of respondents reported a psychiatric disorder. Of these, 89 percent had symptoms of depression and/or anxiety, 8.5 percent had bipolar disorder, and 2.6 percent had schizophrenia spectrum disorder. Among persons reporting at least one mental illness, 48.5 percent had been tested for HIV. The 48.5 percent rate compares to a testing rate of 35 percent among those without mental illness. More specifically, 64 percent of persons with schizophrenia, 63 percent of persons with bipolar disorder, and 47 percent of persons with depression and/or anxiety reported ever being tested for HIV.
"Our study shows that persons with mental illness and/or their care providers recognize that they are at higher risk and should be tested," said senior authorMichael B. Blank, PhD, associate professor in Psychiatry at Penn and co-director of the Penn Mental Health AIDS Research Center. "However, by no means we should be complacent since these results may in large part be due to individual vigilance. The fact is there are few formal prevention and screening efforts targeted at this at-risk population. In light of the fact that mentally ill people are more likely to engage in risky behavior, mental health providers should consider routinely offering HIV/AIDS testing, something that does not typically occur now."
HIV infection and mental illness are often co-occurring health conditions, with nearly half of persons living with HIV having a psychiatric disorder while between 5-23 percent of those with mental illness are infected with HIV.
In addition, the study found that persons aged 25-44, women, racial and ethnic minorities, individuals who are windowed/divorced/separated, those reporting excessive use of alcohol or tobacco, and persons with HIV risk factors were significantly more likely to be tested for HIV than their counterparts.
Separate research has found that mentally ill individuals are more likely than others to engage in high-risk behaviors associated with HIV transmission, including unprotected sexual intercourse, injection drug use, and sex with multiple partners.
"Our finding that persons with mental illness were tested for HIV at a higher rate than those without mental illness is encouraging and consistent with previous analyses," said lead author Baligh R. Yehia MD, MPP, MSHP, assistant professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania and director of the Penn Medicine Program for LGBT Health. "However, the large number of people with mental illness who still have not been tested necessitates increased public health prevention efforts, particularly in light of the increased HIV risk in this population."
The CDC recommends that all persons aged 13-64 be tested for HIV in healthcare settings and that persons with increased risk such as injecting drug users and their sex partners, sex workers, men who have sex with men, and heterosexuals with multiple sex partners be tested at least annually.
Source:
AIDS Patient Care and STDs

Scientists Study Blood Brain Barrier Function in Pediatric Neurological Diseases I

The blood brain barrier (BBB) in the human brain is a very important aspect in human physiology. The human BBB separates circulating blood from the central nervous system, thus protecting the brain from many infections and toxins. But the BBB also blocks the passage of many potentially useful drugs to the brain and it has long stymied scientists who want to learn more about this vital tissue because of the lack of realistic non-human lab models.

 
Even less is known about the BBB in children. There are significant structural and functional differences between the pediatric and adult BBB, but ethical considerations clearly limit research possibilities. So while it is known that the immature brain is especially vulnerable to damage from inflammation as well as from oxygen or blood deprivation and an altered BBB has been linked to cerebral palsy and to complications from traumatic brain injury in children, research to date on these questions has been hampered. 

Now bio engineering researchers at Temple University in Philadelphia have come up with an experimental workaround; a synthetic pediatric blood-brain barrier on a small chip and have tested it successfully using rat brain endothelial cells (RBECs) from rat pups and human endothelial cells. They will describe it at the ASCB/IFCB meeting in Philadelphia on December 8. The model BBB on a chip is the creation of postdoctoral fellow Sudhir Deosarkar in the laboratory of Mohammad Kiani at Temple University in Philadelphia in collaboration with Barbara Krynska from the Shriners Hospitals Pediatric Research Center at Temple's School of Medicine and Balabhaskar Prabhakarpandian from CFD Research Corporation in Huntsville, Alabama. 

Deosarkar calls his physiologically realistic in vitro pediatric BBB model on a chip, the B3C. It has two compartments, one to grow blood vessel cells in and another for cultured brain cells, mimicking the physiology of the BBB. The researchers fabricated the B3C using an optically clear, oxygen permeable polymer, polydimethylsiloxane, on a glass slide with vascular (apical) and tissue (basolateral) compartments. For a proof of principle test, Deosarkar grew the rat brain blood vessel cells on the vascular side of the chip and tested the barrier they formed under a variety of flow conditions with a range of tests including immunofluorescence staining of tight junctions that interconnected the endothelial cells as well as the electrical resistance across the barrier, and by tracking various sized molecules as they crossed to the tissue side of the model. The results were encouraging, Deosarkar reports. Because the interactions of endothelial cells with adjacent brain cells and factors secreted from these cells are necessary for BBB function, permeability of fluorescently tagged molecules was significantly reduced in the presence of factors from brain cells, modeling the of human BBB. 

By culturing RBECs and human endothelial cells under flow conditions, the researchers found that cell-cell junctions they formed accurately mimicked endothelial barrier formation in the brain. Says Deosarkar, "In this study, we have developed a first realistic pediatric BBB model (B3C) using RBECs from rat pups and human endothelial cells which could serve as an in vitro model system for studying BBB function in pediatric neurological diseases as well as for testing novel therapies for these diseases." 
 Source:Temple University

Specific Bacteria in Microbiota Helps Protect from Malaria

In a recent breakthrough research led by Miguel Soares, it was discovered that specific bacterial components in microbiota (human gut) can generate a natural defense mechanism to protect from malaria transmission.

 Over the past few years, the scientific community became aware that humans live under a continuous symbiotic relationship with a vast community of bacteria and other microbes that reside in the gut. These microbes, know as the gut microbiota, do not necessarily cause disease to humans and instead can influence a variety of physiologic functions that are essential to maintain health. Some of these microbes, including specific strains of Escherichia coli that are usual inhabitant of the human gut, express on their surface sugar molecules (known as carbohydrates or glycans). These glycans can be recognized by the human immune system, which results in the production of high levels of circulating natural antibodies in adult individuals. It has been speculated that natural antibodies directed against sugar molecules expressed by the microbiota may also recognize perhaps similar sugar molecules expressed by pathogens, that is, parasites that can cause diseases in humans. 

Bahtiyar Yilmaz, a PhD student of the Instituto Gulbenkian de Ciencia PhD programme in Miguel Soares' laboratory, found that the Plasmodium parasite, the causative agent of malaria, expresses a sugar molecule called alpha-gal, which is also expressed at the surface of a strain of E. coli that is part of the human gut microbiota. In a series of experiments performed in mice, Bahtiyar Yilmaz went on to find that expression of alpha-gal by these bacteria, when resident in the gut, is sufficient to induce the production of natural antibodies that can recognize the same sugar molecule when expressed at the surface of Plasmodium parasites. He then found that these antibodies attach to the alpha-gal sugar at the surface of Plasmodium parasites, immediately after the inoculation in the skin by a mosquito, the vector of malaria transmission. When this occurs the anti-alpha-gal antibodies activate an additional arm of the human immune system, called the complement cascade, which goes on to punch holes and kills the Plasmodium parasite before it can move out of the skin. The protective effect is such that when present at high levels at the time of the mosquito bite, anti-alpha-gal antibodies manage to arrest the transition of the parasite from the skin into the blood stream and by doing so block malaria transmission. 

It was well established before these studies, that only a fraction of all adult individuals that are confronted to the bite of mosquitoes in endemic areas of malaria do become infected by the Plasmodium parasite and eventually go on to contract malaria. This argued that adults might have a natural defense mechanism against malaria transmission, which is in sharp contrast with children under 3-5 years old that are much more susceptible to contract malaria. When analyzing individuals from an endemic area of malaria in Mali, in collaboration with a research team lead by Peter D. Crompton at National Institute of Allergy and Infectious Diseases (Maryland; USA) and at the University of Sciences, Techniques and Technologies of Bamako (Bamako, Mali), the research team lead by Miguel Soares established that those individuals that have the lowest levels of circulating anti-alpha-gal antibodies are also those that are the most susceptible to contract malaria. In contrast those individuals that have the highest levels of circulating anti-alpha-gal antibodies are less susceptible to be infected and to develop malaria. They conclude that the reason why young infants are so susceptible to contract malaria is probably due to the fact that they have not yet generated sufficient levels of circulating natural antibodies directed against the alpha-gal sugar molecule. 

With the goal of overcoming this shortcoming, Bahtiyar Yilmaz found that when mice are vaccinated against a synthetic form of alpha-gal that is rather easy and inexpensive to produce, they produced high levels of circulating anti-alpha-gal antibodies that are highly protective against malaria transmission by mosquitoes. Whether the same "trick" can be applied to humans and in particular to young infants to confer protection against malaria transmission is a "burning question" that remains to be answered. 

It is estimated that 3.4 billion people are at risk of contracting malaria and WHO data from 2012 reveal that about 460,000 African children died from malaria before reaching their fifth birthday. The present study argues that if one can induce the production of antibodies against alpha-gal in those children one may be able to revert these grim numbers. 

Miguel Soares adds: "We observed that children under 3 years old do not have sufficient levels of circulating anti-alpha-gal antibodies, which might be one of the reasons for their exquisite susceptibility to malaria. One of the beauties of the protective mechanism we just discovered is that it can be induced via a standard vaccination protocol, leading to the production of high levels of anti-alpha-gal antibodies that bind and kill the Plasmodium parasite. If we can vaccinate these young children against alpha-gal, many lives might be saved." 

 Source: Instituto Gulbenkian de Ciencia

To Resolve Inflammation, Macrophages Chase Neutrophils Away from Wounds

Macrophages are known for their Pac Man-like ability to gobble up pathogens and cellular debris in order to thwart infection.A new study in The Journal of Cell Biology describes how these immune cells also help resolve inflammation by inducing white blood cells called neutrophils to leave wounded tissue. 

Neutrophils are "first responders" that are attracted to wounds by signaling molecules called reactive oxygen species (ROS) that activate a protein kinase. When neutrophils finish their work, inflammation is partly resolved through apoptosis, or cell suicide, and the subsequent engulfment of the neutrophils' remains by macrophages. But neutrophils can also elect to leave wounded tissue in a process known as reverse migration. Whether macrophages promote this mode of inflammation resolution is unclear. 

Taking advantage of transparent zebrafish larvae, Anna Huttenlocher and colleagues from the University of Wisconsin-Madison found that neutrophils were generally recruited to wounds before macrophages, but, once they arrived, macrophages often contacted neutrophils and appeared to shepherd them away from the damaged tissue. Neutrophils remained in wounds for longer times in zebrafish larvae lacking macrophages, the researchers discovered. Like neutrophils, macrophages were attracted to wounds by ROS and protein kinase signaling, and macrophages lacking the ROS-generating enzyme Nox2 were unable to migrate into wounds and induce the departure of neutrophils. 

Interestingly, patients lacking the human equivalent of Nox2 suffer from recurring infections and exaggerated inflammation, a disorder known as chronic granulomatous disease. This new study suggests that one cause of the patients' symptoms may be the inability of macrophages to migrate to sites of inflammation to induce neutrophil reverse migration and inflammation resolution. 
 Source: