Depression linked to telomere enzyme, aging, chronic disease

Depression linked to telomere enzyme, aging, chronic disease

Now a research team led by Owen Wolkowitz, MD, professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study will be reported today at the annual meeting of the American Psychiatric Association in San Francisco.

Telomerase is an enzyme that lengthens protective end caps on the chromosomes' DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.

The heightened telomerase activity in untreated major depression might represent the body's attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.

The researchers made another discovery that may suggest a protective role for telomerase. Using magnetic resonance imaging (MRI), they found that, in untreated, depressed study participants, the size of the hippocampus, a brain structure that is critical for learning and memory, was associated with the amount of telomerase activity measured in the white blood cells. Such an association at a single point in time cannot be used to conclude that there is a cause-and-effect relationship with telomerase helping to protect the hippocampus, but it is plausible, Wolkowitz said.

Remarkably, the researchers also found that the enzyme's activity went up when some patients began taking an antidepressant. In fact, depressed participants with lower telomerase activity at baseline -- as well as those in whom enzyme activity increased the most with treatment -- were the most likely to become less depressed with treatment.

"Our results are consistent with the beneficial effect of telomerase when it is boosted in animal studies, where it has been associated with the growth of new nerve cells in the hippocampus and with antidepressant-like effects, evidenced by increased exploratory behavior," Wolkowitz said. Wolkowitz cautions that his new findings are preliminary due to the small size of the study and must be confirmed through further research.

The researchers also measured telomere length in the same immune cells. Only very chronically depressed individuals showed telomere shortening, Wolkowitz said.

"The longer people had been depressed, the shorter their telomeres were," he said. "Shortened telomere length has been previously demonstrated in major depression in most, but not all, studies that have examined it. The duration of depression may be a critical factor."

The 20 depressed participants enrolled in the study had been untreated for at least six weeks and had an average lifetime duration of depression of about 13 years. After baseline evaluation and laboratory measures, 16 of the depressed participants were treated with sertraline, a member of the most popular class of anti-depressants, the serotonin-selective-reuptake-inhibitors (SSRIs), and then evaluated again after eight weeks. There were 20 healthy participants who served as controls.

The ongoing study still is accepting depressed participants who are not now taking antidepressants. Wolkowitz's team also studies chronic inflammation and the biochemical phenomenon of oxidative stress, which he said have often been reported in major depression. Wolkowitz is exploring the hypothesis that inflammation and oxidative stress play a role in telomere shortening and accelerated aging in depression.

"New insights into the mechanisms of these processes may well lead to new treatments -- both pharmacological and behavioral -- that will be distinctly different from the current generation of drugs prescribed to treat depression," he said. "Additional studies might lead to simple blood tests that can measure accelerated immune-cell aging."

Wolkowitz's research is funded by the National Institutes of Health. He is on the scientific advisory board of Telome Health, Inc., a private biotechnology company.

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Vast methane-based ecosystem uncovered

Vast methane-based ecosystem uncovered

The seep lies deep in the western North Atlantic Ocean, far from the life-sustaining energy of the sun. Mussels blanketing the the seep rely on bacteria that use the methane to make energy. The process, known as chemosynthesis, forms the basis for life in the harsh environment and could help scientists better understand how organisms can survive under these types of extreme conditions.

"UNCW and FSU have done two previous cruises together and this is perhaps our biggest discovery," said UNCW researcher Dr. Steve Ross. "Studies of this kind and of these communities help scientists understand how life thrives in harsh environments, and perhaps even on other planets."

The new seep discovery is only the third documented seep site on the U.S. Atlantic Coast, and by far the most extensive; the two seep areas at this site are estimated to be at least a kilometer long and in places hundreds of meters across. Sea cucumbers were also seen tucked into the tight mounds of mussels and shrimp swam above them. Many species of fishes, including some with unusual behaviors, were also common around the unique ecosystem..

Stationed aboard NOAA's Ronald H. Brown research vessel, the research teams used the diverse capabilities of the Woods Hole Oceanographic Institution's Remotely Operated Vehicle (ROV), Jason II, to document and study the newly discovered methane seep.. The teams have been able to capture high definition video, sample the sediment at the site, collect live mussels for genetic and reproductive studies, collect large dead shells and rocks for aging analysis, take water samples to examine water chemistry, and sample associated animals to examine food webs.

The seep discovery could potentially play an important role in advancing scientific understanding of hydrocarbon resources and gas hydrates (important possible future energy resources) along the US continental slope .

Major funding for the research expedition was provided by the Bureau of Ocean Energy Management, with NOAA providing funding for the Ronald H. Brown and Jason ROV. US Geological Survey and other collaborators also provided a variety of resources.

TAG:Extreme Survival Fish Marine Biology Sustainability Energy and the Environment Renewable Energy

First genomic survey of human skin fungal diversity

First genomic survey of human skin fungal diversity

Human skin surfaces are complex ecosystems for microorganisms, including fungi, bacteria and viruses, which are known collectively as the skin microbiome. Although fungal infections of the skin affect about 29 million people in the United States, fungi can be slow and hard to grow in laboratories, complicating diagnosis and treatment of even the most common fungal skin conditions, such as toenail infections.

The research team from the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), both parts of NIH, extended their recent genome sequencing study of skin bacteria, using DNA sequencing techniques optimized for identifying fungi. The study appears in the May 22, 2013 early online issue of Nature.

The researchers found that a single type of fungus, belonging to the genus Malassezia, is predominant on the head and trunk. Hands, which harbor a great diversity of bacteria, are home for relatively few types of fungi. In contrast, feet, including toenails, heels and toe webs contain tremendous diversity.

"Applying DNA sequencing to a study of the skin's fungi is the natural progression in understanding microbial life that co-exists on our bodies," said NHGRI Scientific Director Daniel Kastner, M.D., Ph.D. "Along with recent genome sequencing to define bacterial diversity, this analysis of fungal diversity provides a more complete human microbiome picture."

"Fungal communities occupy complex niches, even on the human body," said Heidi Kong, M.D., co-senior author and an investigator in the dermatology branch of NCI's Center for Cancer Research. "By gaining a more complete awareness of the fungal and bacterial ecosystems, we can better address associated skin diseases, including skin conditions which can be related to cancer treatments."

The researchers collected samples at 14 body sites from 10 healthy adults. DNA sequencing of the fungi in the samples identified fragments of DNA, called phylogenetic markers, which can be counted and used to distinguish one type of fungus from another. The sequencing efforts generated more than 5 million markers, from the samples, representing more than 80 fungal types, or genera. In contrast, traditional culturing methods produced 130 colonies of fungi that represented only 18 fungal genera.

In 20 percent of the study participants, the researchers observed problems such as heel and toe web scaling or toenail changes consistent with possible fungal infections. From genome sequencing analysis, the researchers found that different individuals with heel site infections have common fungal communities at that site, while those with toenail infections display tremendously different fungal communities.

"DNA sequencing reveals the great diversity of fungi, even those that are hard to grow in culture," said Julie Segre, Ph.D., co-senior author and senior investigator, NHGRI Genetics and Molecular Biology Branch. Her expertise is the development of microbial DNA sequencing technology. "DNA sequencing enabled us to learn immeasurably more about where fungi predominate as a part of the human skin microbiome."

The researchers identified fungi from two phyla, Ascomycetes and Basidiomycetes, as part of the normal fungal census at the 14 skin sites. The most common genus Malassezia was present in 11 of 14 sites sampled on the body. The researchers found Malassezia fungus on every skin surface of healthy volunteers, whether on the back of the head, behind the ears, in nostrils and on the heels. Heels were also home to many additional fungi, including the genera Aspergillus, Cryptococcus, Rhodotorula, and Epicoccum.

"DNA sequence-based methods of identification enabled us to differentiate among species of fungi and to conclude that the diversity of fungi is highly dependent on the body site rather than the person who is sampled," said Dr. Kong. A dermatologist, Dr. Kong explained why these sites were selected for exploration: "Our study focused on areas of the skin where we commonly find skin diseases that have been associated with fungi."

The most complex site, the heel, is home to about 80 genus-level types of fungi. The researchers found about 60 types in toenail swab samples and 40 types in samples from the webs of the toes. Sites with moderate fungal diversity are inside the bend of the arm, inside of the forearm and palm, with each location supporting 18 to 32 genera of fungi. Surprisingly, head and trunk body sites -- including the back, back of the neck, inside the ears, behind the ears, and between the eyebrows -- have far fewer fungi types, with just two to 10 genera each.

The research team compared fungal diversity data with the skin bacteria on the same healthy adults. They found that while arms have high measures of bacterial diversity, they have lower fungal diversity. They found the reverse to be true for sites on the feet. Core body sites had neither a high bacterial diversity nor a high fungal diversity. The researchers had previously shown that bacterial diversity can be predicted by whether skin is moist, dry or oily. Fungal diversity, instead, seems to depend upon where a particular skin site is on the body.

The researchers observed, in addition, that there is greater similarity in the fungal community structure on the left and right sides of the same person's body compared to the same body parts on any two individuals. Fungal communities also appear to be quite stable over time, with little change when tested on two separate occasions, up to three months apart.

"The data from our study gives us a baseline about normal individuals that we never had before," Dr. Segre said. "The bottom line is your feet are teeming with fungal diversity, so wear your flip flops in locker rooms if you don't want to mix your foot fungi with someone else's fungi."

TAG:Skin Care Human Biology Psoriasis Fungus Microbes and More Microbiology

Largest genetic sequencing study of human disease

Largest genetic sequencing study of human disease

May 22, 2013 — Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.

The exact cause of these diseases -- autoimmune thyroid disease, celiac disease, Crohn's disease, psoriasis, multiple sclerosis and type 1 diabetes- is unknown, but is believed to be a complex combination of genetic and environmental factors. In each disease only a proportion of the heritability is explained by the identified genetic variants. The techniques used to date, have generally identified common (in the population) variants of weak effect.

In this study, using high-throughput sequencing techniques,a global team of scientists sought to identify new variants, including rare and potentially high risk ones, in 25 previously identified risk genes in a sample of nearly 42,000 individuals (24,892 with autoimmune disease and 17,019 controls).

It has been suggested -- in the 'rare-variant synthetic genome-wide association hypothesis' -- that a small number of rare variants in risk genes are likely to be a major cause of the heritability of these conditions. However, the study published today in the journal Nature, suggests that the genetic risk of these diseases more likely involves a complex combination of hundreds of weak-effect variants which are each common in the population.

The authors estimate that rare variants in these risk genes account for only around three per cent of the heritability of these conditions that can be explained by common variants.

David van Heel, Professor of Gastrointestinal Genetics at Barts and The London School of Medicine and Dentistry at Queen Mary and director of the Barts and The London Genome Centre, led the study. He said: "These results suggests that risk for these autoimmune diseases is not due to a few high-risk genetic variations but seems rather due to a random selection from many common genetic variants which each have a weak effect.

"For each disease there are probably hundreds such variants and the genetic risk is likely to come from inheriting a large number of these variants from both parents. If this is the case then it may never be possible to accurately predict an individual's genetic risk of these common autoimmune diseases. However, the results do provide important information about the biological basis of these conditions and the pathways involved, which could lead to the identification new drug targets."

The research utilised high-throughput sequencing techniques performed at the Barts and The London Genome Centre and demonstrated for the first time that the sequencing can call genotypes as accurately as 'gold standard techniques' such as genotyping array platforms. Additional laboratory work was carried out at the Blizard institute at Queen Mary.

Professor Richard Trembath, Vice Principal and Executive Dean for Health at Barts and The London School of Medicine and Dentistry, Queen Mary, and a co-author on the paper said: "The results prompt a re-assessment of the genetic architecture that determines risk for development of common auto-immune disorders and will fuel future careful assessment of regions of the human genome beyond those presently known to confer susceptibility to these important medical conditions."

This study was primarily funded by the Medical Research Council with additional funding from Coeliac UK.

TAG:Personalized Medicine Diseases and Conditions Asthma Genes Cholesterol Chronic Illness

Model of Sun's magnetic field created

Model of Sun's magnetic field created

Scientists have known since the 18th Century that the Sun regularly oscillates between periods of high and low solar activity in an 11-year cycle, but have been unable to fully explain how this cycle is generated.

In the 'Information Age', it has become increasingly important to be able to understand the Sun's magnetic activity, as it is the changes in its magnetic field that are responsible for 'space weather' phenomena, including solar flares and coronal mass ejections. When this weather heads in the direction of Earth it can damage satellites, endanger astronauts on the International Space Station and cause power grid outages on the ground.

The research, published in the journal Nature, explains how the cyclical nature of these large-scale magnetic fields emerges, providing a solution to the mathematical equations governing fluids and electromagnetism for a large astrophysical body.

The mechanism, known as a dynamo, builds on a solution to a reduced set of equations first proposed in the 1950s which could explain the regular oscillation but which appeared to break down when applied to objects with high electrical conductivity. The mechanism takes into account the 'shear' effect of mass movement of the ionised gas, known as plasma, which makes up the Sun. More importantly it does so in the extreme parameter regime that is relevant to astrophysical bodies.

"Previously, dynamos for large, highly conducting bodies such as the Sun would be overwhelmed by small-scale fluctuations in the magnetic field. Here, we have demonstrated a new mechanism involving a shear flow, which served to damp these small-scale variations, revealing the dominant large-scale pattern," said Professor Steve Tobias, from the University of Leeds' School of Mathematics, a co-author of the research.

What is more, this mechanism could be used to describe other large, spinning astronomical bodies with large-scale magnetic fields such as galaxies.

The dynamo was developed through simulations using the high-performance computing facilities located at the University of Leeds.

"The fact that it took 50 years and huge supercomputers shows how complicated the dynamo process really is." said Prof Fausto Cattaneo, from the University of Chicago's Department of Astronomy and Astrophysics.

The presence of spots on the Sun has been known since antiquity, and further analysed after the invention of the telescope by Galileo in the 16th Century. However, their cyclic nature, with periods of high activity (lots of sunspots) and low activity (few sunspots) following each other, was not identified until the 18th Century. At the start of the 20th Century it was then recognised that these sunspots were the result of the Sun's magnetic field. Since then much effort has been devoted to understanding what processes lead to the formation of sunspots and the origin of their cyclic behaviour.

TAG:Sun Solar Flare Astronomy Space Telescopes Space Exploration Northern Lights

Fragile mega-galaxy is missing link in history of cosmos

Fragile mega-galaxy is missing link in history of cosmos

May 22, 2013 — Two hungry young galaxies that collided 11 billion years ago are rapidly forming a massive galaxy about 10 times the size of the Milky Way, according to UC Irvine-led research published Wednesday in the journal Nature.

Capturing the creation of this type of large, short-lived star body is extremely rare -- the equivalent of discovering a missing link between winged dinosaurs and early birds, said the scientists, who relied on the once-powerful Herschel space telescope and observatories around the world. The new mega-galaxy, dubbed HXMM01, "is the brightest, most luminous and most gas-rich submillimeter-bright galaxy merger known," the authors write.

HXMM01 is fading away as fast as it forms, a victim of its own cataclysmic birth. As the two parent galaxies smashed together, they gobbled up huge amounts of hydrogen, emptying that corner of the universe of the star-making gas.

"These galaxies entered a feeding frenzy that would quickly exhaust the food supply in the following hundreds of million years and lead to the new galaxy's slow starvation for the rest of its life," said lead author Hai Fu, a UC Irvine postdoctoral scholar.

The discovery solves a riddle in understanding how giant elliptical galaxies developed quickly in the early universe and why they stopped producing stars soon after. Other astronomers have theorized that giant black holes in the heart of the galaxies blew strong winds that expelled the gas. But cosmologist Asantha Cooray, the UC Irvine team's leader, said that they and colleagues across the globe found definitive proof that cosmic mergers and the resulting highly efficient consumption of gas for stars are causing the quick burnout.

"Finding this type of galaxy is as important as the discovery of the archaeopteryx was in understanding dinosaurs' evolution into birds, because they were both caught at a critical transitional phase," Fu said.

The new galaxy was initially spotted by UC Irvine postdoctoral scholar Julie Wardlow, also with Cooray's group. She noticed "an amazing, bright blob" in images of the so-called cold cosmos -- areas where gas and dust come together to form stars -- recorded by the European Space Agency's Herschel telescope with important contributions from NASA's Jet Propulsion Laboratory in Pasadena. "Herschel captured carpets of galaxies, and this one really stood out."

Follow-up views at a variety of wavelengths were obtained at more than a dozen ground-based observatories, particularly the W. M. Keck Observatory in Hawaii.

TAG:Galaxies Astrophysics Stars Cosmology Astronomy Space Telescopes

Promising new approach to treatment of lung cancer

Promising new approach to treatment of lung cancer

This advance in nanomedicine combines the extraordinarily small size of nanoparticles, existing cancer drugs, and small interfering RNA (siRNA) that shut down the ability of cancer cells to resist attack.

The combination of these forces resulted in the virtual disappearance of lung tumors in experimental animals.

Lung cancer is the leading cancer killer in both men and women. Despite advances in surgery, chemotherapy still plays a major role in its treatment. However, that treatment is constrained by the toxic effects of some drugs needed to combat it and the difficulty of actually getting those drugs into the lungs.

The findings were made by Oleh Taratula at Oregon State University and Tamara Minko and O. Garbuzenko at Rutgers University and the Cancer Institute of New Jersey. They were just published in the Journal of Controlled Release.

"Lung cancer damage is usually not localized, which makes chemotherapy an important part of treatment," said Taratula, an assistant professor in the OSU College of Pharmacy and co-author on this study. "However, the drugs used are toxic and can cause organ damage and severe side effects if given conventionally through intravenous administration.

"A drug delivery system that can be inhaled is a much more efficient approach, targeting just the cancer cells as much as possible," he said. "Other chemotherapeutic approaches only tend to suppress tumors, but this system appears to eliminate it."

A patent is being applied for on the technology, and more testing will be necessary before it is ready for human clinical trials, the researchers said.

The foundation of the new system is a "nanostructured lipid nanocarrier," tiny particles much smaller than a speck of dust that are easily inhaled and also readily attach to cancer cells. This carrier system delivers the anticancer drug. However, it also brings siRNA that makes the cancer cell more vulnerable.

Cancer cells often have two forms of resistance to drugs -- "pump" resistance that tends to pump the drug out of cells, and "nonpump" resistance that helps keep the cell from dying. The siRNA used in this system helps to eliminate both those forms of resistance, and leaves the cancer cell vulnerable to the drug being used to kill it.

By being inhaled, this system also avoids degradation of the chemotherapeutic agents that occurs when they are injected, researchers said. They arrive in more intact form, ready to do their job on lung cancer cells, while minimizing any side effects.

In more conventional chemotherapy for lung cancer, the drugs tend to accumulate in the liver, kidney and spleen, with much less of the drugs ever making it to the lungs. In this study, the amount of the drug delivered to the lungs rose to 83 percent with the inhalation approach, versus 23 percent with injection.

This work was supported by the National Cancer Institute, National Science Foundation, and the Department of Defense.

TAG:Lung Cancer Colon Cancer Cancer Prostate Cancer Lung Disease Diseases and Conditions

Footwear's (carbon) footprint: Bulk of shoes' carbon footprint comes from manufacturing processes

Footwear's (carbon) footprint: Bulk of shoes' carbon footprint comes from manufacturing processes

But what's surprising to researchers isn't the size of a shoe's carbon footprint, but where the majority of that footprint comes from.

The researchers found that more than two-thirds of a running shoe's carbon impact can come from manufacturing processes, with a smaller percentage arising from acquiring or extracting raw materials. This breakdown is expected for more complex products such as electronics, where the energy that goes into manufacturing fine, integrated circuits can outweigh the energy expended in processing raw materials. But for "less-advanced" products -- particularly those that don't require electronic components -- the opposite is often the case.

So why does a pair of sneakers, which may seem like a relatively simple product, emit so much more carbon dioxide in its manufacturing phase?

A team led by Randolph Kirchain, principal research scientist in MIT's Materials Systems Laboratory, and research scientist Elsa Olivetti broke down the various steps involved in both materials extraction and manufacturing of one pair of running shoes to identify hotspots of greenhouse-gas emissions. The group found that much of the carbon impact came from powering manufacturing plants: A significant portion of the world's shoe manufacturers are located in China, where coal is the dominant source of electricity. Coal is also typically used to generate steam or run other processes in the plant itself.

A typical pair of running shoes comprises 65 discrete parts requiring more than 360 processing steps to assemble, from sewing and cutting to injection molding, foaming and heating. Olivetti, Kirchain and their colleagues found that for these small, light components such processes are energy-intensive -- and therefore, carbon-intensive -- compared with the energy that goes into making shoe materials, such as polyester and polyurethane.

The group's results, Kirchain says, will help shoe designers identify ways to improve designs and reduce shoes' carbon footprint. He adds that the findings may also help industries assess the carbon impact of similar consumer products more efficiently.

"Understanding environmental footprint is resource intensive. The key is, you need to put your analytical effort into the areas that matter," Kirchain says. "In general, we found that if you have a product that has a relatively high number of parts and process steps, and that is relatively light [weight], then you want to make sure you don't overlook manufacturing."

Kirchain and his colleagues have published their results in the Journal of Cleaner Production.

The sum of a shoe's parts

In 2010, nearly 25 billion shoes were purchased around the world, the majority of them manufactured in China and other developing countries. As Kirchain and his co-authors write in their paper, "An industry of that scale and geographic footprint has come under great pressure regarding its social and environmental impact."

In response, companies have started to take account of their products' greenhouse-gas contributions, in part by measuring the amount of carbon dioxide associated with every process throughout a product's lifecycle. One such company, ASICS, an athletic equipment company based in Japan, approached Kirchain to perform a lifecycle assessment for a running shoe manufactured in China.

The team took a "cradle-to-grave" approach, breaking down every possible greenhouse gas-emitting step: from the point at which the shoes' raw materials are extracted to the shoes' demise, whether burned, landfilled or recycled.

The researchers divided the shoes' lifecycle into five major stages: materials, manufacturing, usage, transportation and end-of-life. These last three stages, they found, contributed very little to the product's carbon footprint. For example, running shoes, unlike electronics, require very little energy to use, aside from the energy needed to infrequently wash the shoes.

The bulk of emissions, they found, came from manufacturing. While part of the manufacturing footprint is attributable to a facility's energy source, other emissions came from processes such as foaming and injection molding of parts of a sneaker's sole, which expend large amounts of energy in the manufacture of small, lightweight parts. As Kirchain explains it, "You have a lot of effort going into the molding of the material, but you're only getting a very small part out of that process."

"What stood out was this manufacturing burden being on par with materials, which we hadn't seen in similar products," Olivetti adds. "Part of that is because it's a synthetic product. If we were looking at a leather shoe, it would be much more materials-driven because of the carbon intensity of leather production."

An improved design

In tallying the carbon emissions from every part of a running shoe's lifecycle, the researchers were also able to spot places where reductions might be made. For example, they observed that manufacturing facilities tend to throw out unused material. Instead, Kirchain and his colleagues suggest recycling these scraps, as well as combining certain parts of the shoe to eliminate cutting and welding steps. Printing certain features onto a shoe, instead of affixing them as separate fabrics, would also streamline the assembly process.

Kirchain and Olivetti view their results as a guide for companies looking to evaluate the impact of similar products.

"When people are trying for streamlined approaches to [lifecycle assessments], often they put emphasis on the materials impact, which makes a lot of sense," Olivetti says. "But we tried to identify a set of characteristics that would point you to making sure you were also looking at the manufacturing side -- when it matters."

TAG:Electronics Petroleum Materials Science Global Warming Air Quality Energy and the Environment