Superbright, fast X-rays image single layer of proteins

In biology, a protein’s shape is key to understanding how it causes disease or toxicity. Researchers who use X-rays to take snapshots of proteins need a billion copies of the same protein stacked and packed into a neat crystal. Now, scientists using exceptionally bright and fast X-rays can take a picture that rivals conventional methods with a sheet of proteins just one protein molecule thick.Using a type of laser known as XFEL, the technique opens the door to learning the structural details of almost 25 percent of known proteins, many of which have been overlooked due to their inability to stack properly. The team of researchers led by the Department of Energy’s Pacific Northwest and Lawrence Livermore National Laboratories report their results with this unique form of X-ray diffraction in the March issue of the International Union of Crystallography Journal.”In this paper, we’re proving it’s possible to use an XFEL to study individual monolayers of protein,” said PNNL microscopist James Evans. “Just being able to see any diffraction is brand new.”Evans co-led the team of two dozen scientists with LLNL physicist Matthias Frank. The bright, fast X-rays were produced at the Linac Coherent Light Source at SLAC National Accelerator Laboratory in Menlo Park, Calif., the newest of DOE’s major X-ray light source facilities at the national laboratories. LCLS, currently the world’s most powerful X-ray laser, is an X-ray free-electron laser. It produces beams millions of times brighter than earlier X-ray light sources.Coming in at around 8 angstrom resolution (which can make out items a thousand times smaller than the width of a hair), the proteins appear slightly blurry but match the expected view based on previous research. Evans said this level of clarity would allow researchers, in some cases, to see how proteins change their shape as they interact with other proteins or molecules in their environment.To get a clearer view of protein monolayers using XFEL, the team will need to improve the resolution to 1 to 3 angstroms, as well as take images of the proteins at different angles, efforts that are currently underway.Not Your Family’s CrystalResearchers have been using X-ray crystallography for more than 60 years to determine the shape and form of proteins that form the widgets and gears of a living organism’s cells. The conventional method requires, however, that proteins stack into a large crystal, similar to how oranges stack in a crate. …

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Teenage physical fitness reduces the risk of suicidal behavior later in life

June 26, 2013 — Being in good physical shape at 18 years of age can be linked with a reduced risk of attempted suicide later in life. So says a study of over one million Swedish men conducted by researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden.A new, extensive report from the Swedish National Board of Health and Welfare on child and adolescent health shows that teenagers and young adults in Sweden have worse mental health than their age cohorts in other western countries.Another report that is part of a new social welfare study shows that the number of serious suicide attempts among 19-23 year olds with activity compensation has increased from 115 per year to 460 per year in Sweden between 1995-2010.At the same time, the number of suicides in the 10 to 45 age group increased. Even the percentage of young people with no activity compensation who attempted to take their life increased.In order to break this trend, research has now focused on the factors that can prevent mental illness and the risk of suicidal behavior.Researchers at the Sahlgrenska Academy, University of Gothenburg, have been able to use a study of 1,136,527 Swedish men to show that there is a link between exercising as a young person and a reduced risk of suicidal behavior later in life.”Being in poor physical shape at 18 years of age, measured as the test results on an exercise bike during their medical exam for compulsory military service, can be linked to a risk of suicidal behavior as an adult that is 1.8 times greater,” says Margda Waern, researcher at the Sahlgrenska Academy, University of Gothenburg.The study shows that the increased risk was evident even 42 years after the exam for military service.It has previously been shown that physical exercise has a highly positive effect on brain function, e.g. more nerve cells are developed with physical exercise.”The teenage years are a critical period in terms of brain development since this is when social and emotional faculties are established. Therefore, it was important to do a larger study on the importance of physical fitness in terms of suicidal behavior in this age group,” says Maria Åberg, researcher at the Sahlgrenska Academy who led the study together with Professor Margda Waern.In the study, which covers all Swedish men born between 1950 and 1987 who completed the previously mandatory exam, researchers compared the results from physical tests during the exam with the national registers of disease and death.By carefully examining the roughly 340,000 brothers who took part in the study, researchers were able to study how hereditary factors and the home environment affect this relationship.In a much discussed study published in 2012, the researcher group showed that good physical fitness as a teenager can also be linked to decreased risk of severe depression later in life.”But even when we exclude individuals who suffer from severe depression in connection with suicide or attempted suicide, the link between poor physical shape and an increased risk of suicidal behavior remains,” says Margda Waern.While depression is a particularly strong predictor of suicidal behavior in later life, the picture among younger people is complex and many factors are involved.”One theory is that the brain becomes more resistant to different types of stress if you are physically active,” says Maria Åberg.Researchers think that physical exercise should be considered in suicide prevention projects aimed at young people.The new findings are supported by earlier cross-sectional studies where teenagers are interviewed about their physical fitness connected with the risk for suicidal thoughts.

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Sugar solution makes tissues see-through

June 23, 2013 — Japanese researchers have developed a new sugar and water-based solution that turns tissues transparent in just three days, without disrupting the shape and chemical nature of the samples. Combined with fluorescence microscopy, this technique enabled them to obtain detailed images of a mouse brain at an unprecedented resolution.The team from the RIKEN Center for Developmental biology reports their finding today in Nature Neuroscience.Over the past few years, teams in the USA and Japan have reported a number of techniques to make biological samples transparent, that have enabled researchers to look deep down into biological structures like the brain.”However, these clearing techniques have limitations because they induce chemical and morphological damage to the sample and require time-consuming procedures,” explains Dr. Takeshi Imai, who led the study.SeeDB, an aqueous fructose solution that Dr. Imai developed with colleagues Drs. Meng-Tsen Ke and Satoshi Fujimoto, overcomes these limitations.Using SeeDB, the researchers were able to make mouse embryos and brains transparent in just three days, without damaging the fine structures of the samples, or the fluorescent dyes they had injected in them. They could then visualize the neuronal circuitry inside a mouse brain, at the whole-brain scale, under a customized fluorescence microscope without making mechanical sections through the brain.They describe the detailed wiring patterns of commissural fibers connecting the right and left hemispheres of the cerebral cortex, in three dimensions, for the first time.Dr. Imai and colleagues report that they were also able to visualize in three dimensions the wiring of mitral cells in the olfactory bulb, which is involved the detection of smells, at single-fiber resolution.”Because SeeDB is inexpensive, quick, easy and safe to use, and requires no special equipment, it will prove useful for a broad range of studies, including the study of neuronal circuits in human samples,” explain the authors.

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Changes in cell shape may lead to metastasis, not the other way around

June 21, 2013 — A crucial step toward skin cancer may be changes in the genes that control cell shape, report a team of scientists from The Methodist Hospital Research Institute, the Institute of Cancer Research, London, and Harvard Medical School in an upcoming issue of Nature Cell Biology (now online).Using automated high content screening and sophisticated computational modeling, the researchers’ screening and analysis of tens of millions of genetically manipulated cells helped them identify more than a dozen genes that influence cell shape. Their work could lead to a better understanding of how cells become metastatic and, eventually, pinpoint new gene therapy targets for cancer treatment.”We found that by altering the way the cells are grown to better mimic conditions in a living organism, gene expression could have a profound impact on cell shape,” said Zheng Yin, the paper’s lead author and a postdoctoral fellow at the Department of Systems Medicine and Bioengineering of The Methodist Hospital Research Institute (TMHRI). “This matters because many cancer biologists believe metastasis depends in part on the ability of cells to take on different shapes to escape their confines and spread to healthy tissue. We developed a method of identifying and analyzing the shapes of fruit fly cells, then validated and expanded the discoveries in mammal cancer cells..”The scientists began their study in fruit fly immune cells called hemocytes. Under normal conditions, each hemocyte was found to take on just one of five distinct shapes about 98 percent of the time. In contrast to conventional wisdom, other shapes and “intermediate” forms were rare, suggesting genes that control cell shape behave more like light switches than teakettles coming to a slow boil. Genetic manipulation of these cells in a lab setting supported that view as well.Next the group examined human and mouse melanoma cells, which also take on a variety of forms. The researchers identified seven genes that cause cells to take on an especially rounded form, or else an elongated form. One of these genes, PTEN, had a particularly strong impact. When turned off, virtually all cells became elongated or large and rounded, two shapes that can help cancerous cells escape confinement, travel blood vessels, and infiltrate healthy tissues. …

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