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Human Stem Cells Converted to Functional Lung Cells

For the first time, scientists have succeeded in transforming human stem cells into functional lung and airway cells. The advance, reported by Columbia University Medical Center (CUMC) researchers, has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study was published today in the journal Nature Biotechnology.

"Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine," said study leader Hans-Willem Snoeck, MD, PhD, professor of medicine (in microbiology & immunology) and affiliated with the Columbia Center for Translational Immunology and the Columbia Stem Cell Initiative. "Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplants -- that is, transplants that use a patient's own skin cells to generate functional lung tissue."

The research builds on Dr. Snoeck's 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endoderm -- precursors of lung and airway cells. (Human iPS cells closely resemble human ES cells but are generated from skin cells, by coaxing them into taking a developmental step backwards. Human iPS cells can then be stimulated to differentiate into specialized cells -- offering researchers an alternative to human ES cells.)

In the current study, Dr. Snoeck and his colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells (cells that cover the lung surface). The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

The findings have implications for the study of a number of lung diseases, including idiopathic pulmonary fibrosis (IPF), in which type 2 alveolar epithelial cells are thought to play a central role. "No one knows what causes the disease, and there's no way to treat it," says Dr. Snoeck. "Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures."

"In the longer term, we hope to use this technology to make an autologous lung graft," Dr. Snoeck said. "This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient. In this way, rejection problems could be avoided." Dr. Snoeck is investigating this approach in collaboration with researchers in the Columbia University Department of Biomedical Engineering.

"I am excited about this collaboration with Hans Snoeck, integrating stem cell science with bioengineering in the search for new treatments for lung disease," said GordanaVunjak-Novakovic, PhD, co-author of the paper and Mikati Foundation Professor of Biomedical Engineering at Columbia's Engineering School and professor of medical sciences at Columbia University College of Physicians and Surgeons.

Source: Science Daily

R.Sawas

Late starters' still have much to gain by exercising

Taking up exercise in your 60s will still help stave off major ill health and dementia, research suggests.

The study in the British Journal of Sports Medicine followed 3,500 healthy people at or around retirement age.

Those who took up exercise were three times more likely to remain healthy over the next eight years than their sedentary peers.

Exercise cut the risk of heart disease, stroke, diabetes, Alzheimer's disease and depression.

People who took up exercise in their 60s were also less likely to struggle with day-to-day activities such as washing and dressing.

Healthy agers

After eight years of follow-up, a fifth of the participants were defined as healthy - not suffering from any major chronic mental or physical illness.

This group was largely made up of people who always exercised and relative newcomers to exercise. Few were people who did no exercise at all.

Doing regular exercise throughout your life is ideal, say the researchers, but there are health benefits to be had even if you are a late starter.

Lead investigator Dr Mark Hamer, from University College London, said: "The take-home message really is to keep moving when you are elderly.

"It's [a] cliche, but it's a case of use it or lose it. You do lose the benefits if you don't remain active."

In the study, those who had regularly indulged in moderate or vigorous physical activity at least once a week were three to four times more likely to be healthy agers than those who had remained inactive, even after taking into account factors such as smoking.

Dr Hamer says physical activity does not necessarily mean going to the gym or going for a run - gardening or walking to the shops also counts.

The Department of Health recommends all adults, including those over 65, do 150 minutes of physical activity a week.

Doireann Maddock, of the British Heart Foundation, said: "It's well worth getting into the habit of keeping active, as we know it can help reduce the risk of heart disease along with many other conditions.

"Every 10 minutes counts, so even hopping off the bus a couple of stops early or taking a brisk walk on your lunch break will help."

Source : BBC

N.H.Khider

Walnuts are the healthiest nut, say scientists

Eating raw walnuts gives the full benefits of antioxidants.

Walnuts are the healthiest of all the nuts and should be eaten more as part of a healthy diet, US scientists say.

Scientists from Pennsylvania told the American Chemical Society that walnuts contain the highest level of antioxidants compared to other nuts.

Antioxidants are known to help protect the body against disease.

The scientists said that all nuts have good nutritional qualities but walnuts are healthier than peanuts, almonds, pecans and pistachios.

Dr Joe Vinson, from the University of Scranton, analysed the antioxidant levels of nine different types of nuts and discovered that a handful of walnuts contained twice as many antioxidants as a handful of any other commonly eaten nut.

He found that these antioxidants were higher in quality and potency than in any other nut.

Antioxidants are good because they stop the chain reactions that damage cells in the body when oxidation occurs.

Roasted nuts

The antioxidants found in walnuts were also two to 15 times as powerful as vitamin E, which is known to protect the body against damaging natural chemicals involved in causing disease, the study says.

Nuts are known to be healthy and nutritious, containing high-quality protein, lots of vitamins and minerals as well as dietary fibre. They are also dairy and gluten-free.

Previous research has shown that regular consumption of small amounts of nuts can reduce the risk of heart disease, some types of cancer, type two diabetes and other health problems.

Dr Vinson said there was another advantage in choosing walnuts as a source of antioxidants: "The heat from roasting nuts generally reduces the quality of the antioxidants.

"People usually eat walnuts raw or unroasted, and get the full effectiveness of those antioxidants."

Source ; BBC

N.H.Khider

Antibiotics not for running noses, warn doctors

Running noses and green phlegm do not mean patients need antibiotics, say doctors and public health experts.

It was described as a "prevailing myth" that the drugs were needed to treat such infections.

Public Health England and the Royal College of General Practitioners said the symptoms were often caused by viruses.

And the use of antibiotics was leading to resistance, they said.

Public Health England said its own research showed that 40% of people thought antibiotics would help a cough if the phlegm was green, while very few thought it would make a difference to clear-coloured phlegm.

Dr Cliodna McNulty, from the organization, said: "It's a prevailing myth that anyone with green phlegm or snot needs a course of antibiotics to get better.

"Most of the infections that generate lots of phlegm and snot are viral illnesses and will get better on their own although you can expect to feel pretty poorly for a few weeks.

"The problems of antibiotic resistance are growing. Everyone can help by not using antibiotics for the treatment of uncomplicated infections."

Taking antibiotics affects the trillions of bacteria that naturally live in the human body and can lead to resistance.

Dr Maureen Baker, chairwoman of the Royal College of GPs, said: "Overuse of antibiotics is a serious public health concern.

"Infections adapt to antibiotics used to kill them and can ultimately make treatment ineffective so it's crucial that antibiotics are used appropriately."

The green colour in phlegm and snot is the result of a protein made by the immune system to fight infection. The latest advice comes on European Antibiotics Awareness Day.

Source : BBC

N.H.Khider

Evolution of Bitter Taste Sensitivity

It's no coincidence that the expression "to leave a bitter taste in one's mouth" has a double meaning; people often have strong negative reactions to bitter substances, which, though found in healthful foods like vegetables, can also signify toxicity. For this reason, the ability to sense bitterness likely played an important role in human evolution.

A new study by University of Pennsylvania scientists provides new evidence underlining the significance of bitter taste perception. Their work suggests that a genetic mutation that makes certain people sensitive to the taste of a bitter compound appears to have been advantageous for certain human populations in Africa. Yet the reason why this trait was selected may not have to do with just taste. Instead, the molecular receptor under study may also play important roles in immune response or metabolism.

"We're starting to understand that these taste receptors are involved in so many functions other than just oral sensory perception," said Michael Campbell, lead author on the study and a postdoctoral fellow in Penn's Perelman School of Medicine's Department of Genetics.

The study, published in the journal Molecular Biology and Evolution, represents the first time that this bitter-taste sensing gene, TAS2R16, was studied in a large set of ethnically and culturally diverse African populations.

"Because Africa is the site of origin of all modern humans," said Sarah Tishkoff, the study's senior author and a Penn Integrates Knowledge Professor with appointments in the School of Arts and Sciences' Department of Biology and Penn Medicine's Department of Genetics. "Africans are going to have a large amount of diversity and non-Africans are going to have a subset of that diversity. In Africa, you get an opportunity to observe how these genetic variants are influencing phenotypes that you wouldn't have if you were only studying non-Africans."

Campbell, Tishkoff and other Penn researchers collaborated with Paul Breslin of Rutgers University and Monell Chemical Senses Center, as well as scientists from Addis Ababa University, France's Musée de L'Homme, Integral Molecular Inc., the Kenya Medical Research Institutes, Cameroon's Ministry of Scientific Research and Innovation, Tanzania's Muhimbili University of Health and Allied Sciences and the National institute on Deafness and Other Communication Disorders.

The work builds on a previous study by the group, which explored the evolutionary history of a gene called TAS2R38, responsible for the ability to perceive the bitter tasting compound PTC. In that research, published in Molecular Biology and Evolution in 2012, the geneticists discovered that something other than taste perception must have driven the selection of that gene.

The current work examines the related gene TAS2R16, which codes for a molecular receptor that binds salicin. Salicin is a chemical found naturally in willow bark, the source of aspirin. It acts as an anti-inflammatory but in large doses can be toxic. It is also found in many nuts, fruits and vegetables.

To understand the patterns of variation at TAS2R16 in humans globally, the researchers collected DNA from 595 people in 74 populations across Africa with diverse lifestyles, such as pastoralism, hunting-gathering and agriculture. They sequenced the stretch of DNA encompassing the TAS2R16 gene in all of these individuals and also examined previously collected DNA from 94 non-Africans from the Middle East, Europe, East Asia and the Americas and found 15 variants total, most of which were only found in Africa.

In addition, the researchers asked 296 of the Africans sampled to perform "taste tests" of progressively more concentrated solutions of salicin and report when they could detect a bitter taste. The team also performed a cellular analysis, led by Integral Molecular scientists, to see the molecular effects of different TAS2R16 mutations.

"The taste testing shows that the mutations in TAS2R16 had functional significance for the bitter taste perception system," Breslin said. "In this case, the mutation caused a gain of taste function."

When the researchers "mapped" individuals' genetic profiles onto their tasting ability, they found a strong correlation between one of the 15 variants and an increased sensitivity to salicin. The cell-based analysis offered an explanation for this sensitivity: cells with this genetic mutation had nearly twice as many receptors for salicin on their membranes as did cells with other forms of the TAS2R16 gene.

On a population level, the researchers found that the "high-sensitivity" variant for salicin was more prevalent in individuals from East Africa than in those from West Central or Central Africa, and non-Africans possessed only the "high-sensitivity" version of the gene. What's more, in East Africans this high-sensitivity variant, which arose roughly 1.1 million years ago, showed signs of being under a force of natural selection in humans, suggesting it conferred an evolutionary advantage at some point during our past.

"That's another sign that this variant must be tremendously important for human survival because it evolved in our human ancestors so long ago and carried over to us," Campbell said.

The geographic structure of TAS2R16 variants contrasts with the previous work on TAS2R38, variants of which did not appear to fall into any clear geographic pattern. These differences between two genes that both relate to bitter taste perception offer more support to the idea that taste was not the only force driving the evolution of this gene.

"The types of populations we're studying are diverse and they have diverse diets," Tishkoff said, "suggesting that there is likely something else going on here. By getting a handle on how much variation is in these populations, where it is located and what are the particular signatures of selection, it might start giving us clues as to what we should be looking at in terms of the biomedical or physiological significance of these genes."

Source: Science Daily

R.S