DNA Constructs Antenna for Solar Energy

Researchers at Chalmers University of Technology have found an effective solution for collecting sunlight for artificial photosynthesis. By combining self-assembling DNA molecules with simple dye molecules, the researchers have created a system that resembles nature's own antenna system.

Artificial photosynthesis is an exciting area of energy research. A large number of the worlds' energy problems could be resolved if it were possible to recreate the ability plants have to transform solar energy into fuel. Earth receives enough solar energy every hour to satisfy our energy needs for an entire year.
A research team at Chalmers University of Technology has made a nanotechnological breakthrough in the first step required for artificial photosynthesis. The team has demonstrated that it is possible to use self-assembling DNA molecules as scaffolding to create artificial systems that collect light. The results were recently published in the scientific Journal of the American Chemical Society.
Scaffolding in plants and algae consists of a large number of proteins that organise chlorophyll molecules to ensure effective light collection. The system is complicated and would basically be impossible to construct artificially.
"It's all over if a bond breaks," says Jonas Hannestad, PhD of physical chemistry. "If DNA is used instead to organise the light-collecting molecules, the same precision is not achieved but a dynamic self-constructing system arises."
With a system that builds itself, the researchers have begun to approach nature's method. If any of the light-collecting molecules break, it will be replaced with another one a second later. In this sense, it is a self-repairing system as opposed to if molecules had been put there by researchers with synthetic organic chemistry.
The sun's light is moved to a reaction centre in plants and algae so they can synthesise sugars and other energy-rich molecules.
"We can move energy to a reaction centre, but we have not resolved how the reactions themselves are to take place there," says Bo Albinsson, professor of physical chemistry and head of the research team. "This is actually the most difficult part of artificial photosynthesis. We have demonstrated that an antenna can easily be built. We have recreated that part of the miracle."
The Chalmers researchers are combining artificial photosynthesis with DNA nanotechnology. When constructing nano-objects that are billionths of a metre, DNA molecules have proven to function very well as building material. This is because DNA strands have the ability to attach to each other in a predictable manner. As long as the correct assembly instructions are given from the start, DNA strands in a test tube can bend around each other and basically form any structure.
"It's like a puzzle where the pieces only fit together in one specific way," says Bo Albinsson. "That is why it is possible to draw a fairly complex structure on paper and then know basically what it will look like. We subsequently use those traits to control how light collection will take place.
 

Journal Reference:

1. Jakob G. Woller, Jonas K. Hannestad, Bo Albinsson. Self-Assembled Nanoscale DNA–Porphyrin Complex for Artificial Light Harvesting. Journal of the American Chemical Society, 2013; 135 (7): 2759 DOI: 10.1021/ja311828v

Courtesy: ScienceDaily
 

Bigbrain: An Ultra-High Resolution 3-D Roadmap of the Human Brain

A landmark three-dimensional (3-D) digital reconstruction of a complete human brain, called the BigBrain, now for the first time shows the brain anatomy in microscopic detail -- at a spatial resolution of 20 microns, smaller than the size of one fine strand of hair -- exceeding that of existing reference brains presently in the public domain. The new tool is made freely available to the broader scientific community to advance the field of neuroscience.

Researchers from Germany and Canada, who collaborated on the ultra-high resolution brain model, present their work in the 21 June issue of the journal Science.

"The authors pushed the limits of current technology," said Science's senior editor Peter Stern about the international scientific effort. "Such spatial resolution exceeds that of presently available reference brains by a factor of 50 in each of the three spatial dimensions."

The sophisticated modern image processing methods reveal an unprecedented look at the very fine details of the human brain's microstructure, or cellular level. The anatomical tool will allow for three-dimensional cytoarchitectonic mapping of the human brain and serve as an atlas for small cellular circuit data, or single layers or sublayers of the cerebral cortex, explained the researchers.

Until recently, reference brains did not probe further than the macroscopic, or visible, components of the brain. Now, the BigBrain provides a resolution much finer than the typical 1 mm resolution from MRI studies.

The project "has been a tour-de-force to assemble images of over 7,400 individual histological sections, each with its own distortions, rips and tears, into a coherent 3-D volume," said senior author Dr. Alan Evans, a professor at the Montreal Neurological Institute at McGill University in Montreal, Canada. "This dataset allows for the first time a 3-D exploration of human cytoarchitectural anatomy."

Thin sections of a 65-year-old human female brain, which was embedded in paraffin wax, were cut with a special large-scale tool called a microtome. Then, the 20-micrometer thick histological sections were mounted on slides, stained to detect cell structures and finally digitized with a high-resolution flatbed scanner so researchers could reconstruct the high-resolution 3-D brain model. It took approximately 1,000 hours to collect the data. The resulting images reveal differences in the laminar pattern between brain areas.

The new reference brain, which is part of the European Human Brain Project, serves as a powerful tool to facilitate neuroscience research and "redefines traditional maps from the beginning of the 20th century," explained lead author Dr. Katrin Amunts from the Research Centre Jülich and director of the Cecile and Oskar Vogt Institute for Brain Research at the Heinrich Heine University Düsseldorf in Germany. "The famous cytoarchitectural atlases of the early 1900's were simplified drawings of a brain and were based on pure visual analysis of cellular organization patterns," added Dr. Amunts.

Because of the sheer volume of this dataset, the researchers say that there will be a push by those who want to use it to develop new and valuable tools for visualization, data management and analysis.

"We plan to repeat this process in a sample of brains so that we can quantify cytoarchitectural variability," said Dr. Evans. "We will also integrate this dataset with high-resolution maps of white matter connectivity in post-mortem brains. This will allow us to explore the relationship between cortical microanatomy and fiber connectivity," said Dr. Amunts.

"We are planning to integrate our receptor data of the human brain in the reference frame provided by the BigBrain," continued senior co-author Dr. Karl Zilles, who is senior professor of the Jülich Aachen Research Alliance and former director of the Cecile and Oskar Vogt Institute for Brain Research at the Heinrich Heine University Düsseldorf in Germany. "We will also transfer high-resolution maps of quantitative data on the regional and laminar distribution of native receptor complexes to the BigBrain. This will allow us to explore the relationship between cortical microanatomy and key molecules of neurotransmission."

The fine-grained anatomical resolution will allow scientists to gain insights into the neurobiological basis of cognition, language, emotions and other processes, according to the study. The researchers also stated that they plan to extract measurements of cortical thickness to gain insights into understanding aging and neurodegenerative disorders; create cortical thickness maps to compare data from in vivo imaging; integrate gene expression data from the Allen Institute; and generate a brain model with a resolution of 1 micron to capture details of single cell morphology.

Public access of the BigBrain dataset will be provided through the CBRAIN Portal with free registration, stated the researchers

Journal Reference:

1. K. Amunts, C. Lepage, L. Borgeat, H. Mohlberg, T. Dickscheid, M.-E. Rousseau, S. Bludau, P.-L. Bazin, L. B. Lewis, A.-M. Oros-Peusquens, N. J. Shah, T. Lippert, K. Zilles, A. C. Evans. BigBrain: An Ultrahigh-Resolution 3D Human Brain Model. Science, 2013; 340 (6139): 1472 DOI: 10.1126/science.1235381

Courtesy: ScienceDaily

Alzheimer's Disease Protein Controls Movement in Mice

Researchers in Berlin and Munich, Germany and Oxford, United Kingdom, have revealed that a protein well known for its role in Alzheimer's disease controls spindle development in muscle and leads to impaired movement in mice when the protein is absent or treated with inhibitors. The results, which are published in The EMBO Journal, suggest that drugs under development to target the beta-secretase-1 protein, which may be potential treatments for Alzheimer's disease, might produce unwanted side effects related to defective movement.

Alzheimer's disease is the most common form of dementia found in older adults. The World Health Organization estimates that approximately 18 million people worldwide have Alzheimer's disease. The number of people affected by the disease may increase to 34 million by 2025. Scientists know that the protein beta-secretase-1 or Bace1, a protease enzyme that breaks down proteins into smaller molecules, is involved in Alzheimer's disease. Bace1 cleaves the amyloid precursor protein and generates the damaging Abeta peptides that accumulate as plaques in the brain leading to disease. Now scientists have revealed in more detail how Bace1 works.
"Our results show that mice that lack Bace1 proteins or are treated with inhibitors of the enzyme have difficulties in coordination and walking and also show reduced muscle strength," remarked Carmen Birchmeier, one of the authors of the paper, Professor at the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and an EMBO Member. "In addition, we were able to show that the combined activities of Bace1 and another protein, neuregulin-1 or Nrg1, are needed to sustain the muscle spindles in mice and to maintain motor coordination."
Muscle spindles are sensory organs that are found throughout the muscles of vertebrates. They are able to detect how muscles stretch and convey the perception of body position to the brain. The researchers used genetic analyses, biochemical studies and interference with pharmacological inhibitors to investigate how Bace1 works in mice. "If the signal strength of a specific form of neuregulin-1 known as IgNrg1 is gradually reduced, increasingly severe defects in the formation and maturation of muscle spindles are observed in mice. Furthermore, it appears that Bace1 is required for full IgNrg1 activity. The graded loss of IgNrg1 activity results in the animals having increasing difficulties with movement and coordination," says Cyril Cheret, the first author of the work.
Drug developers are interested in stopping the Bace1 protein in its tracks because it represents a promising route to treat Alzheimer's disease. If the protein were inhibited, it would interfere with the generation of the smaller damaging proteins that accumulate in the brain as amyloid plaques and would therefore provide some level of protection from the effects of the disease. "Our data indicate that one unwanted side effect of the long-term inhibition of Bace1 might be the disruption of muscle spindle formation and impairment of movement. This finding is relevant to scientists looking for ways to develop drugs that target the Bace1 protein and should be considered," says Birchmeier. Several Bace1 inhibitors are currently being tested in phase II and phase III clinical trials for the treatment of Alzheimer's disease.
 

Journal Reference:

1. Cyril Cheret, Michael Willem, Florence R Fricker, Hagen Wende, Annika Wulf-Goldenberg, Sabina Tahirovic, Klaus-Armin Nave, Paul Saftig, Christian Haass, Alistair N Garratt, David L Bennett, Carmen Birchmeier. Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles. The EMBO Journal, 2013; DOI: 10.1038/emboj.2013.146

 

 Courtesy: ScienceDaily

Brain Memory

Memory improved in mice injected with a small, drug-like molecule discovered by UCSF San Francisco researchers studying how cells respond to biological stress.

The same biochemical pathway the molecule acts on might one day be targeted in humans to improve memory, according to the senior author of the study, Peter Walter, PhD, UCSF professor of biochemistry and biophysics and a Howard Hughes Investigator.
The discovery of the molecule and the results of the subsequent memory tests in mice were published in eLife, an online scientific open-access journal, on May 28, 2013.
In one memory test included in the study, normal mice were able to relocate a submerged platform about three times faster after receiving injections of the potent chemical than mice that received sham injections.
The mice that received the chemical also better remembered cues associated with unpleasant stimuli -- the sort of fear conditioning that could help a mouse avoid being preyed upon.
Notably, the findings suggest that despite what would seem to be the importance of having the best biochemical mechanisms to maximize the power of memory, evolution does not seem to have provided them, Walter said.
"It appears that the process of evolution has not optimized memory consolidation; otherwise I don't think we could have improved upon it the way we did in our study with normal, healthy mice," Walter said.
The memory-boosting chemical was singled out from among 100,000 chemicals screened at the Small Molecule Discovery Center at UCSF for their potential to perturb a protective biochemical pathway within cells that is activated when cells are unable to keep up with the need to fold proteins into their working forms.
However, UCSF postdoctoral fellow Carmela Sidrauski, PhD, discovered that the chemical acts within the cell beyond the biochemical pathway that activates this unfolded protein response, to more broadly impact what's known as the integrated stress response. In this response, several biochemical pathways converge on a single molecular lynchpin, a protein called eIF2 alpha.
Scientists have known that in organisms ranging in complexity from yeast to humans different kinds of cellular stress -- a backlog of unfolded proteins, DNA-damaging UV light, a shortage of the amino acid building blocks needed to make protein, viral infection, iron deficiency -- trigger different enzymes to act downstream to switch off eIF2 alpha.
"Among other things, the inactivation of eIF2 alpha is a brake on memory consolidation," Walter said, perhaps an evolutionary consequence of a cell or organism becoming better able to adapt in other ways.
Turning off eIF2 alpha dials down production of most proteins, some of which may be needed for memory formation, Walter said. But eIF2 alpha inactivation also ramps up production of a few key proteins that help cells cope with stress.
Study co-author Nahum Sonenberg, PhD, of McGill University previously linked memory and eIF2 alpha in genetic studies of mice, and his lab group also conducted the memory tests for the current study.
The chemical identified by the UCSF researchers is called ISRIB, which stands for integrated stress response inhibitor. ISRIB counters the effects of eIF2 alpha inactivation inside cells, the researchers found.
"ISRIB shows good pharmacokinetic properties [how a drug is absorbed, distributed and eliminated], readily crosses the blood-brain barrier, and exhibits no overt toxicity in mice, which makes it very useful for studies in mice," Walter said. These properties also indicate that ISRIB might serve as a good starting point for human drug development, according to Walter.
Walter said he is looking for scientists to collaborate with in new studies of cognition and memory in mouse models of neurodegenerative diseases and aging, using ISRIB or related molecules.
In addition, chemicals such as ISRIB could play a role in fighting cancers, which take advantage of stress responses to fuel their own growth, Walter said. Walter already is exploring ways to manipulate the unfolded protein response to inhibit tumor growth, based on his earlier discoveries.
At a more basic level, Walter said, he and other scientists can now use ISRIB to learn more about the role of the unfolded protein response and the integrated stress response in disease and normal physiology.
Additional UCSF study authors are Diego Acosta-Alvear, PhD, Punitha Vedantham, PhD, Brian Hearn, PhD, Ciara Gallagher, PhD, Kenny Ang, PhD, Chris Wilson, PhD, Voytek Okreglak, PhD, Byron Hann, MD, PhD, Michelle Arkin, PhD, and Adam Renslo, PhD. Other authors are Han Li, PhD, and Avi Ashkenazi, PhD, from Genentech; and, Karim Nader, PhD, Karine Gamache, and Arkady Khoutorsky, PhD, from McGill University. The study was funded by the Howard Hughes Medical Institute.

Journal Reference:

1. C. Sidrauski, D. Acosta-Alvear, A. Khoutorsky, P. Vedantham, B. R. Hearn, H. Li, K. Gamache, C. M. Gallagher, K. K.-H. Ang, C. Wilson, V. Okreglak, A. Ashkenazi, B. Hann, K. Nader, M. R. Arkin, A. R. Renslo, N. Sonenberg, P. Walter. Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife, 2013; 2 (0): e00498 DOI: 10.7554/eLife.00498#sthash.ev68BZ7D.dpuf

Courtesy: ScienceDaily

Odors from human skin cells can be used to identify melanoma

According to new research from the Monell Center and collaborating institutions, odors from human skin cells can be used to identify melanoma, the deadliest form of skin cancer. In addition to detecting a unique odor signature associated with melanoma cells, the researchers also demonstrated that a nanotechnology-based sensor could reliably differentiate melanoma cells from normal skin cells. The findings suggest that non-invasive odor analysis may be a valuable technique in the detection and early diagnosis of human melanoma.

Melanoma is a tumor affecting melanocytes, skin cells that produce the dark pigment that gives skin its color. The disease is responsible for approximately 75 percent of skin cancer deaths, with chances of survival directly related to how early the cancer is detected. Current detection methods most commonly rely on visual inspection of the skin, which is highly dependent on individual self-examination and clinical skill.
The current study took advantage of the fact that human skin produces numerous airborne chemical molecules known as volatile organic compounds, or VOCs, many of which are odorous. "There is a potential wealth of information waiting to be extracted from examination of VOCs associated with various diseases, including cancers, genetic disorders, and viral or bacterial infections," notes George Preti, PhD, an organic chemist at Monell who is one of the paper's senior authors.
In the study, published online ahead of print in the Journal of Chromatography B, researchers used sophisticated sampling and analytical techniques to identify VOCs from melanoma cells at three stages of the disease as well as from normal melanocytes. All the cells were grown in culture.
The researchers used an absorbent device to collect chemical compounds from air in closed containers containing the various types of cells. Then, gas chromatography-mass spectrometry techniques were used to analyze the compounds and identified different profiles of VOCs emitting from melanoma cells relative to normal cells.
Both the types and concentrations of chemicals were affected. Melanoma cells produced certain compounds not detected in VOCs from normal melanocytes and also more or less of other chemicals. Further, the different types of melanoma cells could be distinguished from one another.
Noting that translation of these results into the clinical diagnostic realm would require a reliable and portable sensor device, the researchers went on to examine VOCs from normal melanocytes and melanoma cells using a previously described nano-sensor.
Constructed of nano-sized carbon tubes coated with strands of DNA, the tiny sensors can be bioengineered to recognize a wide variety of targets, including specific odor molecules. The nano-sensor was able to distinguish differences in VOCs from normal and several different types of melanoma cells.
"We are excited to see that the DNA-carbon nanotube vapor sensor concept has potential for use as a diagnostic. Our plan is to move forward with research into skin cancer and other diseases," said A.T. Charlie Johnson, PhD, Professor of Physics at the University of Pennsylvania, who led the development of the olfactory sensor.
Together, the findings provide proof-of-concept regarding the potential of the two analytical techniques to identify and detect biomarkers that distinguish normal melanocytes from different melanoma cell types.
"This study demonstrates the usefulness of examining VOCs from diseases for rapid and noninvasive diagnostic purposes," said Preti. "The methodology should also allow us to differentiate stages of the disease process."
Current studies are focusing on analysis of VOCs from tumor sites of patients diagnosed with primary melanoma.

Journal Reference:

1. Jae Kwak, Michelle Gallagher, Mehmet Hakan Ozdener, Charles J. Wysocki, Brett R. Goldsmith, Amaka Isamah, Adam Faranda, Steven S. Fakharzadeh, Meenhard Herlyn, A.T. Charlie Johnson, George Preti. Volatile biomarkers from human melanoma cells. Journal of Chromatography B, 2013; DOI: 10.1016/j.jchromb.2013.05.007

Courtesy: ScienceDaily

Menopause May Be an Unintended Outcome of Men's Preference for Younger Mates

After decades of laboring under other theories that never seemed to add up, a team led by biologist Rama Singh has concluded that what causes menopause in women is men.

Singh, an evolutionary geneticist, backed by computer models developed by colleagues Jonathan Stone and Richard Morton, has determined that menopause is actually an unintended outcome of natural selection -- the result of its effects having become relaxed in older women.
Over time, human males have shown a preference for younger women in selecting mates, stacking the Darwinian deck against continued fertility in older women, the researchers have found.
"In a sense it is like aging, but it is different because it is an all-or-nothing process that has been accelerated because of preferential mating," says Singh, a professor in McMaster's Department of Biology whose research specialties include the evolution of human diversity.
Stone is an associate professor in the Department of Biology and associate director of McMaster's Origins Institute, whose themes include the origins of humanity, while Morton is a professor emeritus in Biology.
While conventional thinking has held that menopause prevents older women from continuing to reproduce, in fact, the researchers' new theory says it is the lack of reproduction that has given rise to menopause.
Their work appears in the online, open-access journal PLOS Computational Biology.
Menopause is believed to be unique to humans, but no one had yet been able to offer a satisfactory explanation for why it occurs, Singh says.
The prevailing "grandmother theory" holds that women have evolved to become infertile after a certain age to allow them to assist with rearing grandchildren, thus improving the survival of kin. Singh says that does not add up from an evolutionary perspective.
"How do you evolve infertility? It is contrary to the whole notion of natural selection. Natural selection selects for fertility, for reproduction -- not for stopping it," he says.
The new theory holds that, over time, competition among men of all ages for younger mates has left older females with much less chance of reproducing. The forces of natural selection, Singh says, are concerned only with the survival of the species through individual fitness, so they protect fertility in women while they are most likely to reproduce.
After that period, natural selection ceases to quell the genetic mutations that ultimately bring on menopause, leaving women not only infertile, but also vulnerable to a host of health problems.
"This theory says that natural selection doesn't have to do anything," Singh says. "If women were reproducing all along, and there were no preference against older women, women would be reproducing like men are for their whole lives."
The development of menopause, then, was not a change that improved the survival of the species, but one that merely recognized that fertility did not serve any ongoing purpose beyond a certain age.
For the vast majority of other animals, fertility continues until death, Singh explains, but women continue to live past their fertility because men remain fertile throughout their lives, and longevity is not inherited by gender.
Singh points out that if women had historically been the ones to select younger mates, the situation would have been reversed, with men losing fertility.
The consequence of menopause, however, is not only lost fertility for women, but an increased risk of illness and death that arises with hormonal changes that occur with menopause. Singh says a benefit of the new research could be to suggest that if menopause developed over time, that ultimately it could also be reversed.

Journal Reference:

1. Richard A. Morton, Jonathan R. Stone, Rama S. Singh. Mate Choice and the Origin of Menopause. PLoS Computational Biology, 2013; 9 (6): e1003092 DOI: 10.1371/journal.pcbi.1003092

Courtesy: ScienceDaily

How Birds Lost Their Penises

In animals that reproduce by internal fertilization, as humans do, you'd think a penis would be an organ you couldn't really do without, evolutionarily speaking. Surprisingly, though, most birds do exactly that, and now researchers reporting in the Cell Press journal Current Biology on June 6 have figured out where, developmentally speaking, birds' penises have gone.

It turns out that land fowl, which have only rudimentary penises as adults, have normally developing penises as early embryos. Later in development, however, the birds turn on a genetic program that leads their budding penises to stop growing and then wither away.
"Regulation of the balance between cell proliferation and cell death is essential for controlled growth and development," said Martin Cohn of the Howard Hughes Medical Institute and University of Florida, Gainesville. "Too much cell division or too little cell death can lead to overgrowth or mis-regulated growth, as in cancer. If the balance is tipped in the other direction, deficient cell division or excess cell death can lead to underdevelopment or even absence of a tissue or organ.
"Our discovery shows that reduction of the penis during bird evolution occurred by activation of a normal mechanism of programmed cell death in a new location, the tip of the emerging penis."
A critical gene in the process is one called Bmp4. In chicken development, Bmp4 switches on and the birds' developing genitals shrink away. In more well-endowed ducks and emus, that gene stays off and their penises continue to grow.
It's not entirely clear why chickens and other birds would have lost their penises, said graduate student Ana Herrera, lead author of the study, but it may be that the loss leaves hens with greater control over their reproductive lives.
The findings could have implications for understanding evolutionary loss more broadly. (Think of snakes and their lost limbs, as another example.) They might yield some answers to medical questions as well.
"Genitalia are one of the fastest-evolving organs in animals, from mollusks to mammals," Cohn said. "It is also the case that genitalia are affected by birth defects more than almost any other organ. Dissecting the molecular basis of the naturally occurring variation generated by evolution can lead to discoveries of new mechanisms of embryonic development, some of which are totally unexpected. This allows us to not only understand how evolution works but also gain new insights into possible causes of malformations."
 

Journal Reference:

1. Ana M. Herrera, Simone G. Shuster, Claire L. Perriton, Martin J. Cohn. Developmental Basis of Phallus Reduction during Bird Evolution. Current Biology, 2013; DOI: 10.1016/j.cub.2013.04.062

Courtesy: ScienceDaily
 

Alzheimer's, Schizophrenia, Autism Now Have New Research Tool: Mature Brain Cells Derived from Skin Cells

Difficult-to-study diseases such as Alzheimer's, schizophrenia, and autism now can be probed more safely and effectively thanks to an innovative new method for obtaining mature brain cells called neurons from reprogrammed skin cells.

According to Gong Chen, the Verne M. Willaman Chair in Life Sciences and professor of biology at Penn State University and the leader of the research team, "the most exciting part of this research is that it offers the promise of direct disease modeling, allowing for the creation, in a Petri dish, of mature human neurons that behave a lot like neurons that grow naturally in the human brain." Chen added that the method could lead to customized treatments for individual patients based on their own genetic and cellular information. The research will be published in the journal Stem Cell Research.
"Obviously, we don't want to remove someone's brain cells to experiment on, so recreating the patient's brain cells in a Petri dish is the next best thing for research purposes and drug screening," Chen said. Chen explained that, in earlier work, scientists had found a way to reprogram skin cells from patients to become unspecialized or undifferentiated pluripotent stem cells (iPSCs). "A pluripotent stem cell is a kind of blank slate," Chen explained. "During development, such stem cells differentiate into many diverse, specialized cell types, such as a muscle cell, a brain cell, or a blood cell. So, after generating iPSCs from skin cells, researchers then can culture them to become brain cells, or neurons, which can be studied safely in a Petri dish."
Now, in their new research, Chen and his team have found a way to differentiate iPSCs into mature human neurons much more effectively, generating cells that behave similarly to neurons in the brain. Chen explained that, in their natural environment, neurons are always found in close proximity to star-shaped cells called astrocytes, which are abundant in the brain and help neurons to function properly. "Because neurons are adjacent to astrocytes in the brain, we predicted that this direct physical contact might be an integral part of neuronal growth and health," Chen explained.
To test this hypothesis, Chen and his colleagues began by culturing iPSC-derived neural stem cells, which are stem cells that have the potential to become neurons. These cells were cultured on top of a one-cell-thick layer of astrocytes so that the two cell types were physically touching each other.
"We found that these neural stem cells cultured on astrocytes differentiated into mature neurons much more effectively," Chen said, contrasting them with other neural stem cells that were cultured alone in a Petri dish. "It was almost as if the astrocytes were cheering the stem cells on, telling them what to do, and helping them fulfill their destiny to become neurons."
To demonstrate the superiority of the neurons grown next to astrocytes, Chen and his co-authors used an electrophysiology recording technique to show that the cells grown on astrocytes had many more synaptic events -- signals sent out from one nerve cell to the others. In another experiment, after growing the neural stem cells next to astrocytes for just one week, the researchers showed that the newly differentiated neurons start to fire action potentials -- the rapid electrical excitation signal that occurs in all neurons in the brain. In a final test, the team members added human neural stem cells to a mixture with mouse neurons. "We found that, after just one week, there was a lot of 'cross-talk' between the mouse neurons and the human neurons," Chen said. He explained that "cross-talk" occurs when one neuron contacts its neighbors and releases a chemical called a neurotransmitter to modulate its neighbor's activity.
"Previous researchers could only obtain brain cells from deceased patients who had suffered from diseases such as Alzheimer's, schizophrenia, and autism," Chen said. "Now, researchers can take skin cells from living patients -- a safe and minimally invasive procedure -- and convert them into brain cells that mimic the activity of the patient's own brain cells." Chen added that, by using this method, researchers also can figure out how a particular drug will affect a particular patient's own brain cells, without needing the patient to try the drug -- eliminating the risk of serious side effects. "The patient can be his or her own guinea pig for the design of his or her own treatment, without having to be experimented on directly," Chen said.
In addition to Chen, other researchers who contributed to this study include Xin Tang, Li Zhou, and Alecia M. Wagner from Penn State; Maria C.N. Marchetto and Fred H. Gage from the Salk Institute; and Alysson R. Muotri from the University of California at San Diego.
The research was funded by the Penn State Stem Cell Fund, the National Institutes of Health, the JPB Foundation, the Mathers Foundation, the McDonnell Foundation, and the California Institute for Regenerative Medicine.

Journal Reference:

1. Xin Tang, Li Zhou, Alecia M. Wagner, Maria C.N. Marchetto, Alysson R. Muotri, Fred H. Gage, Gong Chen. Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells. Stem Cell Research, 2013; DOI: 10.1016/j.scr.2013.05.002

Courtesy: ScienceDaily

'Sex Superbug' More Dangerous Than AIDS? Rumors of New Infection False

A "sex superbug" originally found in Japan in 2011 was allegedly discovered in Hawaii last week, causing fear that the antibiotic-resistant strain of gonorrhea may spread. Now, reports claim that the infection found on patients is not nearly as dangerous as once thought. 

The "sex superbug," known scientifically as H041, and was discovered when a Japanese sex worker contracted gonorrhea in 2011. Unlike other strains of gonorrhea, which could be treated with some antibiotics, this new strain could not be stopped.

"This might be a lot worse than AIDS in the short run because the bacteria is more aggressive and will affect more people quickly," Alan Christianson, a doctor of naturopathic medicine, told UPI. "Getting gonorrhea from this strain might put someone into septic shock and death in a matter of days."

Hawaii state officials then confirmed two more cases of the sex superbug May 1, or so they thought. Because the patients were not responding to initial treatments, Center for Disease Control and Prevention workers believed it was H041.

"It's an emergency situation," William Smith, executive director of the National Coalition of STD Directors, told CNBC. "As time moves on, it's getting more hazardous."

However, it was soon revealed that the gonorrhea in Hawaii was not as dangerous as H041. It resisted initial treatments, but after follow-up appointments, both patients were cleared of their infection.

 "There is no multi-drug super resistant superbug yet in Hawaii or the United States," said Peter Whiticir of the State Department of Health's STD/AIDS Prevention Control branch.

Although the sex superbug has not reared its head outside of Japan, the need for prevention and awareness is still high.

"We don't have the superbug in Hawaii that I repeat again, but I think it does raise people's consciousness that gonorrhea is out there, there are new strains that are developing and evolving and we need to be aware of that and protect ourselves," Whiticir added.

Courtesy: By Daniel Distant , Christian Post Reporter

http://www.christianpost.com/news/sex-superbug-more-dangerous-than-aids-rumors-of-new-infection-false-95486/

Potential New Way to Suppress Tumor Growth Discovered

Researchers at the University of California, San Diego School of Medicine, with colleagues at the University of Rochester Medical Center, have identified a new mechanism that appears to suppress tumor growth, opening the possibility of developing a new class of anti-cancer drugs.

Writing in this week's online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), Willis X. Li, PhD, a professor in the Department of Medicine at UC San Diego, reports that a particular form of a signaling protein called STAT5A stabilizes the formation of heterochromatin (a form of chromosomal DNA), which in turn suppresses the ability of cancer cells to issue instructions to multiply and grow.

Specifically, Li and colleagues found that the unphosphorylated form of STAT promotes and stabilizes heterochromatin, which keeps DNA tightly packaged and inaccessible to transcription factors. "Therefore, genes 'buried' in heterochromatin are not expressed," explained Li.

Phosphorylation is a fundamental cellular function in which a phosphate group is added to a protein or molecule, causing it to turn it on or off or to alter its function. An unphosphorylated STAT lacks this phosphate group.

Li said that in previous studies with fruit flies, the unphosphorylated form of STAT caused chromatin to condense into heterochromatin, while the phosphorylated version prompted dispersal and loss of heterochromatin, furthering gene expression.

"Unphosphorylated STAT promotes and stabilizes heterochromatin formation, which in turn suppresses gene transcription," said Li. "When we expressed either HP1 (the central component of heterochromatin) or unphosphorylated STAT5A in human cancer cells, many genes important for cancer growth are suppressed. These cancer cells do not grow as fast or big as their control parental cancer cells in mouse xenograft models."

Most of the known tumor suppressors, such as p53 or Rb, function by inhibiting cell cycle progression or by spurring cell death, or apoptosis. Li said their findings reveal a potential new way to inhibit cancer gene expression, and may represent a new class of tumor suppressors.

"We are in the process of identifying small molecule drugs that may promote heterochromatin formation without stopping cell division or causing cell death," he said. "These drugs, if found, may be effective in treating cancers with fewer side effects."

Co-authors are Xiaoyu Hu, Amy Tsurumi and Hartmut Land, Department of Biomedical Genetics, University of Rochester Medical Center; Pranabananda Dutta, Jinghong Li and Jingtong Wang, Department of Medicine, UCSD.

Funding for this research came, in part, from the National Institutes of Health grants R01CA131326 and RO1CA138249 and a Leukemia & Lymphoma Society Research Scholar grant

Journal Reference:

1. Xiaoyu Hu, Pranabananda Dutta, Amy Tsurumi, Jinghong Li, Jingtong Wang, Hartmut Land, and Willis X. Li. Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth. PNAS, 2013 DOI: 10.1073/pnas.1221243110

Courtesy: ScienceDaily

Enzyme from Wood-Eating Gribble Could Help Turn Waste Into Biofuel

Scientists have discovered a new enzyme that could prove an important step in the quest to turn waste (such as paper, scrap wood and straw) into liquid fuel. To do this they turned to the destructive power of tiny marine wood-borers called 'gribble', which have been known to destroy seaside piers.

 

Using advanced biochemical analysis and X-ray imaging techniques, researchers from the University of York, University of Portsmouth and the National Renewable Energy Laboratory in the USA have determined the structure and function of a key enzyme used by gribble to break down wood. The findings, published in PNAS, will help the researchers to reproduce the enzymes effects on an industrial scale in a bid to create sustainable liquid biofuels.
To create liquid fuel from woody biomass, such as wood and straw, the polysaccharides (sugar polymers) that make up the bulk of these materials have to be broken down into simple sugars. These are then fermented to produce liquid biofuels. This is a difficult process and making biofuels in this way is currently too expensive.
To find more effective and cheaper ways of converting wood to liquid fuel, scientists are studying organisms that can break down wood in hope of developing industrial processes to do the same.
Gribble are of interest as they are voracious consumers of wood and have all the enzymes needed for its digestion. The enzymes attach to a long chain of complex sugars and chop off small soluble molecules that can be easily digested or fermented. The researchers identified a cellulase (an enzyme that converts cellulose into glucose) from gribble that has some unusual properties and used the latest imaging technology to understand more about it.
The research team leader, Professor Simon McQueen-Mason, from the Centre for Novel Agricultural Products at the University of York, explains: "Enzymes are proteins that serve as catalysts, in this case one that degrades cellulose. Their function is determined by their three-dimensional shape, but these are tiny entities that cannot be seen with high power microscopes. Instead, we make crystals of the proteins, where millions of copies of the protein are arrayed in the same orientation."
Dr John McGeehan, a structural biologist from the University of Portsmouth team, said: "Once we succeeded in the tricky task of making crystals of the enzyme, we transported them to the Diamond Light Source, the UK's national synchrotron science facility. Rather than magnify the enzyme with a lens as in a standard microscope, we fired an intense beam of X-rays at the crystals to generate a series of images that can be transformed into a 3D model. The Diamond synchrotron produced such good data that we could visualise the position of every single atom in the enzyme. Our US colleagues then used powerful supercomputers, called Kraken and Red Mesa, to model the enzyme in action. Together these results help to reveal how the cellulose chains are digested into glucose."
This information will help the researchers to design more robust enzymes for industrial applications. While similar cellulases have been found in wood-degrading fungi, the enzyme from gribble shows some important differences. In particular, the gribble cellulase is extremely resistant to aggressive chemical environments and can work in conditions seven times saltier than sea water. Being robust in difficult environments means that the enzymes can last much longer when working under industrial conditions and so less enzyme will be needed.
Professor McQueen-Mason explained: "This is the first functionally characterised animal enzyme of this type and provides us with a previously undiscovered picture of how they work.
"While this enzyme looks superficially similar to equivalent ones from fungi, closer inspection highlights structural differences that give it special features, for example, the enzyme has an extremely acidic surface and we believe that this is one of the features that contributes to its robustness."
The ultimate aim is to reproduce the effect of this enzyme on an industrial scale. Rather than trying to get the cellulase from gribble, the team have transferred the genetic blueprint of this enzyme to an industrial microbe that can produce it in large quantities, in the same way that enzymes for biological washing detergents are made. By doing this they hope to cut the costs of turning woody materials into biofuels.
Professor McQueen-Mason added: "The robust nature of the enzymes makes it compatible for use in conjunction with sea water, which would lower the costs of processing. Lowering the cost of enzymes is seen as critical for making biofuels from woody materials cost effective. Its robustness would also give the enzymes a longer working life and allow it to be recovered and re-used during processing."
The work is part of the BBSRC Sustainable Bioenergy Centre (BSBEC), a £24M investment that brings together six world-class research programmes to develop the UK's bioenergy research capacity. Funding from a BBSRC USA Partnering Award was instrumental in forming a highly synergistic collaboration with the US DOE funded research team at NREL.
Douglas Kell, BBSRC's Chief Executive, said: "This is an exciting step in realising the potential of these important enzymes. If we can harness them effectively, waste materials could be used to make sustainable fuels. It's a double bonus; avoiding competition with land for food production as well as utilising unused materials from timber and agricultural industries."
 

Journal Reference:

1. Marcelo Kern, John E. McGeehan, Simon D. Streeter, Richard N. A. Martin, Katrin Besser, Luisa Elias, Will Eborall, Graham P. Malyon, Christina M. Payne, Michael E. Himmel, Kirk Schnorr, Gregg T. Beckham, Simon M. Cragg, Neil C. Bruce, and Simon J. McQueen-Mason. Structural characterization of a unique marine animal family 7 cellobiohydrolase suggests a mechanism of cellulase salt tolerance. PNAS, June 3, 2013 DOI: 10.1073/pnas.1301502110

Courtesy: ScienceDaily
 

A Step Closer to Artificial Livers: Researchers Identify Compounds That Help Liver Cells Grow Outside Body

Prometheus, the mythological figure who stole fire from the gods, was punished for this theft by being bound to a rock. Each day, an eagle swept down and fed on his liver, which then grew back to be eaten again the next day.

Modern scientists know there is a grain of truth to the tale, says MIT engineer Sangeeta Bhatia: The liver can indeed regenerate itself if part of it is removed. However, researchers trying to exploit that ability in hopes of producing artificial liver tissue for transplantation have repeatedly been stymied: Mature liver cells, known as hepatocytes, quickly lose their normal function when removed from the body.
"It's a paradox because we know liver cells are capable of growing, but somehow we can't get them to grow" outside the body, says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT, a senior associate member of the Broad Institute and a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.
Now, Bhatia and colleagues have taken a step toward that goal. In a paper appearing in the June 2 issue of Nature Chemical Biology, they have identified a dozen chemical compounds that can help liver cells not only maintain their normal function while grown in a lab dish, but also multiply to produce new tissue.
Cells grown this way could help researchers develop engineered tissue to treat many of the 500 million people suffering from chronic liver diseases such as hepatitis C, according to the researchers.
Lead author of the paper is Jing (Meghan) Shan, a graduate student in the Harvard-MIT Division of Health Sciences and Technology. Members of Bhatia's lab collaborated with researchers from the Broad Institute, Harvard Medical School and the University of Wisconsin.
Large-scale screen
Bhatia has previously developed a way to temporarily maintain normal liver-cell function after those cells are removed from the body, by precisely intermingling them with mouse fibroblast cells. For this study, funded by the National Institutes of Health and Howard Hughes Medical Institute, the research team adapted the system so that the liver cells could grow, in layers with the fibroblast cells, in small depressions in a lab dish. This allowed the researchers to perform large-scale, rapid studies of how 12,500 different chemicals affect liver-cell growth and function.
The liver has about 500 functions, divided into four general categories: drug detoxification, energy metabolism, protein synthesis and bile production. David Thomas, an associate researcher working with Todd Golub at the Broad Institute, measured expression levels of 83 liver enzymes representing some of the most finicky functions to maintain.
After screening thousands of liver cells from eight different tissue donors, the researchers identified 12 compounds that helped the cells maintain those functions, promoted liver cell division, or both.
Two of those compounds seemed to work especially well in cells from younger donors, so the researchers -- including Robert Schwartz, an IMES postdoc, and Stephen Duncan, a professor of human and molecular genetics at the University of Wisconsin -- also tested them in liver cells generated from induced pluripotent stem cells (iPSCs). Scientists have tried to create hepatocytes from iPSCs before, but such cells don't usually reach a fully mature state. However, when treated with those two compounds, the cells matured more completely.
Bhatia and her team wonder whether these compounds might launch a universal maturation program that could influence other types of cells as well. Other researchers are now testing them in a variety of cell types generated from iPSCs.
In future studies, the MIT team plans to embed the treated liver cells on polymer tissue scaffolds and implant them in mice, to test whether they could be used as replacement liver tissues. They are also pursuing the possibility of developing the compounds as drugs to help regenerate patients' own liver tissues, working with Trista North and Wolfram Goessling of Harvard Medical School.
Eric Lagasse, an associate professor of pathology at the University of Pittsburgh, says the findings represent a promising approach to overcoming the difficulties scientists have encountered in growing liver cells outside of the body. "Finding a way of growing functional hepatocytes in cell culture would be a major breakthrough," says Lagasse, who was not part of the research team.
Making connections
Bhatia and colleagues have also recently made progress toward solving another challenge of engineering liver tissue, which is getting the recipient's body to grow blood vessels to supply the new tissue with oxygen and nutrients. In a paper published in the Proceedings of the National Academy of Sciences in April, Bhatia and Christopher Chen, a professor at the University of Pennsylvania, showed that if preformed cords of endothelial cells are embedded into the tissue, they will rapidly grow into arrays of blood vessels after the tissue is implanted.
To achieve this, Kelly Stevens in the Bhatia lab worked with Peter Zandstra at the University of Toronto to design a new system that allows them to create 3-D engineered tissue and precisely control the placement of different cell types within the tissue. This approach, described in the journal Nature Communications in May, allows the engineered tissue to function better with the host tissue.
"Together, these papers offer a path forward to solve two of the longstanding challenges in liver tissue engineering -- growing a large supply of liver cells outside the body and getting the tissues to graft to the transplant recipient," Bhatia says.
 

Story Source:
The above story is reprinted from materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton.

Courtesy: ScienceDaily