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Rescooped by Dr. Stefan Gruenwald from DNA and RNA research!

Super-resolution microscopy reveals mechanics of tiny ‘DNA walkers’ 

Super-resolution microscopy reveals mechanics of tiny ‘DNA walkers’  | Amazing Science |

Researchers have introduced a new type of “super-resolution” microscopy and used it to discover the precise walking mechanism behind tiny structures made of DNA that could find biomedical and industrial applications.


The researchers also demonstrated how the “DNA walker” is able to release an anticancer drug, representing a potential new biomedical technology, said Jong Hyun Choi, an associate professor of mechanical engineering at Purdue University.


Synthetic nanomotors and walkers are intricately designed systems that draw chemical energy from the environment and convert it into mechanical motion. However, because they are too small to be observed using conventional light microscopes, researchers have been unable to learn the precise steps involved in the walking mechanisms, knowledge essential to perfecting the technology.


“If you cannot resolve or monitor these walkers in action, you will be unable to understand their mechanical operation,” Choi said.

He led a Purdue team that has solved this problem by developing a super-resolution microscopy system designed to study the DNA walkers. The new findings appeared in the journal Science Advances on Jan. 20, 2017.

Via Integrated DNA Technologies
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A molecular microscope: Super - high - resolution snapshot of RNA folding

A molecular microscope: Super - high - resolution snapshot of RNA folding | Amazing Science |

Northwestern University engineers have invented a tool to make a super-high-resolution representation of RNA folding as it is being synthesized. It could potentially lead to future discoveries in basic biology, gene expression, RNA viruses, and disease.


Made up of long chains of nucleotides, RNA is responsible for many tasks in the cellular environment, including making proteins, transporting amino acids, gene expression, and carrying messages between DNA and ribosomes. To accomplish all these tasks, RNA folds into complex structures — “one of the biggest, most essential pieces of biology that we know comparatively nothing about,” said Julius B. Lucks, Ph.D, an associate professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering.


RNA folding is an essential requirement to life, but is difficult to investigate because the process occurs rapidly and is extremely hard to measure. Existing technology to image RNA folding is very-low-resolution and can’t image RNA’s individual components rapidly enough to capture these processes.


Instead, Lucks’s technology combines two existing components: a next-generation sequencing technique, which is typically used for sequencing human genomes, and a chemistry technique to turn RNA structure measurements into big data.


“Instead of treating it like a genome sequencer, we’re treating it like a molecular microscope to get a massive snapshot,” Lucks said. The technique captures the RNA-folding pathway in a massive dataset. Lucks’s group then uses computational tools to mine and organize the data, which reveals points where the RNA folds and what happens after it folds.


From the structural information that they gather, the researchers can reconstruct a movie of the RNA folding process. The team plans to make the data-analysis component open source, so researchers anywhere can download and run the program.


Lucks and his team have already used the technology to view the folding of a ribo-switch, a segment of RNA that acts as a genetic “light switch” to turn protein expression on or off in response to a molecular signal, in this case fluoride.

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Watching the brain in action real-time

Watching the brain in action real-time | Amazing Science |

Watching millions of neurons in the brain interacting with each other is the ultimate dream of neuroscientists! A new imaging method now makes it possible to observe the activation of large neural circuits, currently up to the size of a small-animal brain, in real time and three dimensions. Researchers at the Helmholtz Zentrum München and the Technical University of Munich have recently reported on their new findings in Nature’s journal ‘Light: Science & Applications’.


Nowadays it is well recognized that most brain functions may not be comprehended through inspection of single neurons. To advance meaningfully, neuroscientists need the ability to monitor the activity of millions of neurons, both individually and collectively. However, such observations were so far not possible due to the limited penetration depth of optical microscopy techniques into a living brain.

A team headed by Prof. Dr. Daniel Razansky, a group leader at the Institute of Biological and Molecular Imaging (IBMI), Helmholtz Zentrum München, and Professor of Molecular Imaging Engineering at the Technical University of Munich, has now found a way to address this challenge. The new method is based on the so-called optoacoustics*, which allows non-invasive interrogation of living tissues at centimeter scale depths.

”We discovered that optoacoustics can be made sensitive to the differences in calcium ion concentrations** resulting from neural activity and devised a rapid functional optoacoustic neuro-tomography (FONT) system that can simultaneously record signals from a very large number of neurons”, said Dr. Xosé Luis Deán-Ben, first author of the study. Experiments performed by the scientists in brains of adult zebrafish (Danio rerio) expressing genetically encoded calcium indicator GCaMP5G demonstrated, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the longstanding penetration barrier of optical imaging in opaque brains. The technique was also able to trace neural activity during unrestrained motion of the animals.

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'Radical' new microscope lens combines high resolution with large field of view

'Radical' new microscope lens combines high resolution with large field of view | Amazing Science |

Optical system can study sub-cellular processes in large biological specimens.


A new microscope lens that offers the unique combination of a large field of view with high resolution has been created by researchers in the UK. The new "mesolens" for confocal microscopes can create 3D images of much larger biological samples than was previously possible – while providing detail at the sub-cellular level. According to the researchers, the ability to view whole specimens in a single image could assist in the study of many biological processes and ensure that important details are not overlooked.


Laser-scanning confocal microscopes are an important tool in modern biological sciences. They emerged in the 1980s as an improvement on fluorescence microscopes, which view specimens that have been dyed with a substance that emits light when illuminated. Standard fluorescence microscopes are not ideal because they pick up fluorescence from behind the focal point, creating images with blurry backgrounds.


To eliminate the out-of-focus background, confocal microscopes use a small spot of illuminating laser light and a tiny aperture so that only light close to the focal plane is collected. The laser is scanned across the specimen and many images are taken to create the full picture. Due to the small depth of focus, confocal microscopes are also able to focus a few micrometres through samples to build up a 3D image.


In microscopy there is a trade-off between resolution and the size of the specimen that can be imaged, or field-of-view – you either have a large field-of-view and low resolution or a small field-of-view and high resolution. Current confocal microscopes struggle to image large specimens, because low magnification produces poor resolution.


"Normally, when a large object is imaged with a low-magnification lens, rays of light are collected from only a small range of angles (i.e. the lens has a low numerical aperture)," explains Gail McConnell from the Centre for Biophotonics at the University of Strathclyde, in Glasgow. "This reduces the resolution of the image and has an even more serious effect in increasing the depth of focus, so all the cells in a tissue specimen are superimposed and you cannot see them individually." Large objects can be imaged by stitching smaller images together. But variations in illumination and focus affect the quality of the final image.


McConnell and colleagues set out to design a lens that could image larger samples, while retaining the detail produced by confocal microscopy. They focused on creating a lens that could be used to image an entire 12.5 day-old mouse embryo – a specimen that is typically about 5 mm across. This was to "facilitate the recognition of developmental abnormalities" in such embryos, which "are routinely used to screen human genes that are suspected of involvement in disease", says McConnell.

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Super-resolution microscope builds 3-D images by mapping negative space

Super-resolution microscope builds 3-D images by mapping negative space | Amazing Science |

Scientists at The University of Texas at Austin have demonstrated a method for making three-dimensional images of structures in biological material under natural conditions at a much higher resolution than other existing methods. The method may help shed light on how cells communicate with one another and provide important insights for engineers working to develop artificial organs such as skin or heart tissue. The research is described today in the journal Nature Communications.


The scientists, led by physicist Ernst-Ludwig Florin, used their method, called thermal noise imaging, to capture nanometer-scale images of networks of collagen fibrils, which form part of the connective tissue found in the skin of animals. A nanometer is a billionth of a meter or about one-hundred-thousandth of the width of a human hair. Examining collagen fibrils at this scale allowed the scientists to measure for the first time key properties that affect skin's elasticity, something that could lead to improved designs for artificial skin or tissues.


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Underwater microscope provides views of ocean-floor sea creatures in their natural setting

Underwater microscope provides views of ocean-floor sea creatures in their natural setting | Amazing Science |

The Homo sapiens view of our world is all a matter of perspective, and we need to remember that we’re among the larger creatures on Earth. At around 1.7 meters in length, we’re much closer in size to the biggest animals that have ever lived – 30-meter-long blue whales – than the viruses and bacteria that are less than one-millionth our size.


Our relative size and their invisibility to our naked eye makes it easy to forget that there are vastly more of those little guys than us – not just in number, but also in mass and volume. And they’re vital to the health of our planet. For example, every other breath of oxygen you take is courtesy of the photosynthetic bacteria that live in the ocean.


As early microscope pioneer Antony Van Lewenhook discovered approximately 350 years ago, these little “animalcules” are in almost every nook and cranny you can think of on Earth. But until now, we haven’t been able to study most microscopic forms of ocean life in their native marine habitats at sufficient resolution to discern many of their miniature features. This is important, as there are thousands of different millimeter-sized underwater creatures we previously couldn’t study unless they were removed and brought to the lab.


Our new Benthic Underwater Microscope (BUM) changes that. In building our underwater microscopes, we are inspired by oceanographer Victor Smetacek’s question of whether an in situ computerized telemicroscope could “do for microbial ecology what Galileo’s telescope did for astronomy.” Simply put, we hope so. Underwater microscopy can help scientists tackle research questions in new ways. Using the BUM, we’ve already seen some amazing new coral behaviors.

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Research note: Yale unveils 3D view of the world inside of cells

Research note: Yale unveils 3D view of the world inside of cells | Amazing Science |

New generations of microscopy have opened up a dazzling world that exists in the interior of new cells. But even the best of the new technology has had a trouble of recording the depth of cellular structures – until now.


Yale University researchers, employing some tricks of powerful astronomy telescopes, have discovered a way to view in three dimensions tiny structures within cells such as mitochondria, the cellular power packs, and nuclear membranes that envelope DNA. In accompanying movie, researchers recorded three-dimensional representations of 19 paternal and maternal mouse chromosomes by using colored fluorescent tags attached to proteins that bind them together. The research paper was published online July 7, 2016, in the journal Cell.

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New imaging method reveals nanoscale details about DNA

New imaging method reveals nanoscale details about DNA | Amazing Science |

Researchers have developed a new enhanced DNA imaging technique that can probe the structure of individual DNA strands at the nanoscale. Since DNA is at the root of many disease processes, the technique could help scientists gain important insights into what goes wrong when DNA becomes damaged or when other cellular processes affect gene expression.


The new imaging method builds on a technique called single-molecule microscopy by adding information about the orientation and movement of fluorescent dyes attached to the DNA strand.

W. E. Moerner, Stanford University, USA, is the founder of single-molecule spectroscopy, a breakthrough method from 1989 that allowed scientists to visualize single molecules with optical microscopy for the first time. Of the 2014 Nobel Laureates for optical microscopy beyond the diffraction limit (Moerner, Hell & Betzig), Moerner and Betzig used single molecules to image a dense array of molecules at different times.


In The Optical Society's journal for high impact research, Optica, the research team led by Moerner describes their new technique and demonstrates it by obtaining super-resolution images and orientation measurements for thousands of single fluorescent dye molecules attached to DNA strands.


"You can think of these new measurements as providing little double-headed arrows that show the orientation of the molecules attached along the DNA strand," said Moerner. "This orientation information reports on the local structure of the DNA bases because they constrain the molecule. If we didn't have this orientation information the image would just be a spot."


A strand of DNA is a very long, but narrow string, just a few nanometers across. Single-molecule microscopy, together with fluorescent dyes that attach to DNA, can be used to better visualize this tiny string. Until now, it was difficult to understand how those dyes were oriented and impossible to know if the fluorescent dye was attached to the DNA in a rigid or somewhat loose way.


Adam S. Backer, first author of the paper, developed a fairly simple way to obtain orientation and rotational dynamics from thousands of single molecules in parallel. "Our new imaging technique examines how each individual dye molecule labeling the DNA is aligned relative to the much larger structure of DNA," said Backer. "We are also measuring how wobbly each of these molecules is, which can tell us whether this molecule is stuck in one particular alignment or whether it flops around over the course of our measurement sequence."

Via Mariaschnee
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Rescooped by Dr. Stefan Gruenwald from Limitless learning Universe!

World's first scanning helium microscope unveiled

World's first scanning helium microscope unveiled | Amazing Science |
Australian researchers build a world-first prototype of a new microscope that will open scientific doors.

Via Mariaschnee, CineversityTV
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New hybrid microscope offers unparalleled capabilities: Vibrations identify materials' composition

New hybrid microscope offers unparalleled capabilities: Vibrations identify materials' composition | Amazing Science |

A microscope being developed at the Department of Energy's Oak Ridge National Laboratory will allow scientists studying biological and synthetic materials to simultaneously observe chemical and physical properties on and beneath the surface. The Hybrid Photonic Mode-Synthesizing Atomic Force Microscope is unique, according to principal investigator Ali Passian of ORNL's Quantum Information System group. As a hybrid, the instrument, described in a paper published in Nature Nanotechnology, combines the disciplines of nanospectroscopy and nanomechanical microscopy.


"Our microscope offers a noninvasive rapid method to explore materials simultaneously for their chemical and physical properties," Passian said. "It allows researchers to study the surface and subsurface of synthetic and biological samples, which is a capability that until now didn't exist."


ORNL's instrument retains all of the advantages of an atomic force microscope while simultaneously offering the potential for discoveries through its high resolution and subsurface spectroscopic capabilities.


"The originality of the instrument and technique lies in its ability to provide information about a material's chemical composition in the broad infrared spectrum of the chemical composition while showing the morphology of a material's interior and exterior with nanoscale -- a billionth of a meter -- resolution," Passian said.


Researchers will be able to study samples ranging from engineered nanoparticles and nanostructures to naturally occurring biological polymers, tissues and plant cells.

The first application as part of DOE's BioEnergy Science Center was in the examination of plant cell walls under several treatments to provide submicron characterization. The plant cell wall is a layered nanostructure of biopolymers such as cellulose. Scientists want to convert such biopolymers to free the useful sugars and release energy.


An earlier instrument, also invented at ORNL, provided imaging of poplar cell wall structures that yielded unprecedented topological information, advancing fundamental research in sustainable biofuels.


Because of this new instrument's impressive capabilities, the researcher team envisions broad applications. "An urgent need exists for new platforms that can tackle the challenges of subsurface and chemical characterization at the nanometer scale," said co-author Rubye Farahi. "Hybrid approaches such as ours bring together multiple capabilities, in this case, spectroscopy and high-resolution microscopy."


Looking inside, the hybrid microscope consists of a photonic module that is incorporated into a mode-synthesizing atomic force microscope. The modular aspect of the system makes it possible to accommodate various radiation sources such as tunable lasers and non-coherent monochromatic or polychromatic sources.

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New handheld miniature microscope could ID cancer cells in doctor’s offices and operating rooms

New handheld miniature microscope could ID cancer cells in doctor’s offices and operating rooms | Amazing Science |

A miniature handheld microscope being developed by University of Washington mechanical engineers could allow neurosurgeons to differentiate cancerous from normal brain tissue at cellular level in real time in the operating room and determine where to stop cutting.

The new technology is intended to solve a critical problem in brain surgery: to definitively distinguish between cancerous and normal brain cells, during an operation, neurosurgeons would have stop the operation and send tissue samples to a pathology lab — where they are typically frozen, sliced, stained, mounted on slides and investigated under a bulky microscope.

Developed in collaboration with Memorial Sloan Kettering Cancer Center, Stanford University and the Barrow Neurological Institute, the new microscope is outlined in an open-access paper published in January in the journalBiomedical Optics Express.

“Surgeons don’t have a very good way of knowing when they’re done cutting out a tumor,” said senior author Jonathan Liu, UW assistant professor of mechanical engineering. “They’re using their sense of sight, their sense of touch, and pre-operative images of the brain — and oftentimes it’s pretty subjective. “Being able to zoom and see at the cellular level during the surgery would really help them to accurately differentiate between tumor and normal tissues and improve patient outcomes.”

The handheld microscope, roughly the size of a pen, combines technologies in a novel way to deliver high-quality images at faster speeds than existing devices. Researchers expect to begin testing it as a cancer-screening tool in clinical settings next year.

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Rescooped by Dr. Stefan Gruenwald from Bioscience News - GEG Tech top picks!

For the first time: The structure of DNA made visible

For the first time: The structure of DNA made visible | Amazing Science |

Enzo di Fabrizio - Professor at King Abdullah University of Science and Technology (KAUST), Saudi Arabia - and his team have developed a new technique to produce a direct image of the DNA helix and its inner structure. This is the first time scientists have ever been able to produce an image of DNA that allows a direct visual evaluation of quantitative and qualitative characteristics of the building blocks of life. The study is thought to open a whole new field of genetics research and nanobiology, giving the world a new tool to understand how proteins and other biomolecules interact within the DNA and the epigenetic influences.

Fabrizio and his team have produced the very first direct image of a DNA strand with resolution 20 times better than that achieved by Di Fabrizio in 2012. This record resolution (1,5 Å) allows an unprecedented reading of the DNA structural molecules, showing quantitative and qualitative characteristics of the sugar-phosphate backbone, the inner C-G A-T paired bases, down to the hydrogen bonds connecting the nucleotides. Other quantitative measures of the helix geometry, such as the grooves and the tilting, were also inferred and successfully compared to X-ray diffraction measures. The results of this research will be published today on Science Advances.

Enzo di Fabrizio explains why it took so long to actually see DNA. “A direct image of DNA is difficult to obtain for two reasons: the elements composing the DNA molecules have a very low contrast and there is an intrinsic difficulty in preparing the sample while maintaining its pristine shape and size. Our new technique overcomes both problems.” To obtain the DNA image Di Fabrizio used a high resolution transmission electron microscope (HRTEM) that allowed the imaging of a suspended single DNA molecule at room temperature with no need for additional treatment that could cause disturbance to the original structure of the strand.

The outcome of this research opens the door to a deeper understanding of the dramatic impact that epigenetic factors have on genetic materials. “DNA isn’t everything” Di Fabrizio stresses “two identical genes can express different proteins with very different characteristics due to a simple methyl group placed between the bases. These differences are not due to genetic mutations but to the activation or deactivation of the gene encoding.” Di Fabrizio says. Epigenetic influences are triggered by “environmental factors” such as diet, chemical exposure and stress-induced metabolic alterations and now, for the first time, we can measure details of base couple methylation or phosphorylation thanks to the new preparation method for HRTEM imaging. “This is seminal research that we hope will open the way to a deeper understanding of the DNA functioning, epigenetics and DNA-protein interaction giving also mutual inputs to molecular dynamics” Di Fabrizio concludes.

Via BigField GEG Tech
BigField GEG Tech's curator insight, September 2, 2015 11:10 AM

From 1952, DNA was sequenced, modified and extensively studied, but no technique was able to produce clear direct images of DNA. Now, researchers have developed a new technique to produce a direct image of the DNA helix and its inner structure.

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Rice University's new electron microscope will capture images at subnanometer resolution

Rice University's new electron microscope will capture images at subnanometer resolution | Amazing Science |

Rice University, renowned for nanoscale science, has installed microscopes that will allow researchers to peer deeper than ever into the fabric of the universe. The Titan Themis scanning/transmission electron microscope, one of the most powerful in the United States, will enable scientists from Rice as well as academic and industrial partners to view and analyze materials smaller than a nanometer — a billionth of a meter — with startling clarity.

The new microscope has the ability to take images of materials at angstrom-scale (one-tenth of a nanometer) resolution, about the size of a single hydrogen atom. Images will be captured with a variety of detectors, including X-ray, optical and multiple electron detectors and a 4K-resolution camera, equivalent to the number of pixels in the most modern high-resolution televisions. The microscope gives researchers the ability to create three-dimensional structural reconstructions and carry out electric field mapping of subnanoscale materials.

“Seeing single atoms is exciting, of course, and it’s beautiful,” said Emilie Ringe, a Rice assistant professor of materials science and nanoengineering and of chemistry. “But scientists saw single atoms in the ’90s, and even before. Now, the real breakthrough is that we can identify the composition of those atoms, and do it easily and reliably.” Ringe’s research group will operate the Titan Themis and a companion microscope that will image larger samples.

Electron microscopes use beams of electrons rather than rays of light to illuminate objects of interest. Because the wavelength of electrons is so much smaller than that of photons, the microscopes are able to capture images of much smaller things with greater detail than even the highest-resolution optical microscope.

“The beauty of these newer instruments is their analytical capabilities,” Ringe said. “Before, in order to see single atoms, we had to work a machine for an entire day and get it just right and then take a picture and hold our breath. These days, seeing atoms is routine.

“And now we can probe a particular atom’s chemical composition. Through various techniques, either via scattering intensity, X-rays emission or electron-beam absorption, we can figure out, say, that we’re looking at a palladium atom or a carbon atom. We couldn’t do that before.”

Ringe said when an electron beam ejects a bound electron from a target atom, it creates an empty site. “That can be filled by another electron within the atom, and the energy difference between this electron and the missing electron is emitted as an X-ray,” she said. “That X-ray is like a fingerprint, which we can read. Different types of atoms have different energies.” 

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Compact new microscope chemically identifies micrometer-sized particles

Compact new microscope chemically identifies micrometer-sized particles | Amazing Science |

A new, ;ow-cost, ten-times-higher-resolution spectroscopy technique could allow for detection of microscopic amounts of chemicals for applications in security, law enforcement, and research.


MIT researchers have developed a radical design for a low-cost, miniaturized microscope that can chemically identify individual micrometer-sized particles. It could one day be used in airports or other high-security venues as a highly sensitive and low-cost way to rapidly screen people for microscopic amounts of potentially dangerous materials. It could also be used for scientific analysis of very small samples or for measuring the optical properties of materials.


In an open-access paper in the journal Optics Letters, from The Optical Society (OSA), the researchers demonstrated their new “photothermal modulation of Mie scattering” (PMMS) microscope by measuring infrared spectra of individual 3-micrometer spheres made of silica or acrylic. The new technique uses a simple optical setup consisting of compact components that will allow the instrument to be miniaturized into a portable device about the size of a shoebox.


The new microscope’s use of visible wavelengths for imaging gives it a spatial resolution of around 1 micrometer, compared to the roughly 10-micrometer resolution of traditional infrared spectroscopy methods. This increased resolution allows the new technique to distinguish and identify individual particles that are extremely small and close together.*


“If there are two very different particles in the field of view, we’re able to identify each of them,” said Stolyarov. “This would never be possible with a conventional infrared technique because the image would be indistinguishable.”


“The most important advantage of our new technique is its highly sensitive, yet remarkably simple design,” said Ryan Sullenberger, associate staff at MIT Lincoln Labs and first author of the paper. “It provides new opportunities for nondestructive chemical analysis while paving the way towards ultra-sensitive and more compact instrumentation.”

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Computer simulations model the crowded cytoplasm of a bacterial cell in atomistic detail

Computer simulations model the crowded cytoplasm of a bacterial cell in atomistic detail | Amazing Science |

Biological macromolecules function in highly crowded cellular environments. The structure and dynamics of proteins and nucleic acids are well characterized in vitro, but in vivo crowding effects remain unclear. Using molecular dynamics simulations of a comprehensive atomistic model cytoplasm scientists found that protein-protein interactions may destabilize native protein structures, whereas metabolite interactions may induce more compact states due to electrostatic screening. Protein-protein interactions also resulted in significant variations in reduced macromolecular diffusion under crowded conditions, while metabolites exhibited significant two-dimensional surface diffusion and altered protein-ligand binding that may reduce the effective concentration of metabolites and ligands in vivo.


Metabolic enzymes showed weak non-specific association in cellular environments attributed to solvation and entropic effects. These effects are expected to have broad implications for the in vivo functioning of biomolecules.


This work is a first step towards physically realistic in silico whole-cell models that connect molecular with cellular biology.



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Rescooped by Dr. Stefan Gruenwald from Mineralogy, Geochemistry, Mineral Surfaces & Nanogeoscience!

Infrared vibrational nanocrystallography and nanoimaging

Infrared vibrational nanocrystallography and nanoimaging | Amazing Science |
Molecular solids and polymers can form low-symmetry crystal structures that exhibit anisotropic electron and ion mobility in engineered devices or biological systems. The distribution of molecular orientation and disorder then controls the macroscopic material response, yet it is difficult to image with conventional techniques on the nanoscale.
Scientists now have demonstrated a new form of optical nanocrystallography that combines scattering-type scanning near-field optical microscopy with both optical antenna and tip-selective infrared vibrational spectroscopy. From the symmetry-selective probing of molecular bond orientation with nanometer spatial resolution, they determined crystalline phases and orientation in aggregates and films of the organic electronic material perylenetetracarboxylic dianhydride. Mapping disorder within and between individual nanoscale domains, the correlative hybrid imaging of nanoscale heterogeneity provides insight into defect formation and propagation during growth in functional molecular solids.

Via Ath Godelitsas
Ath Godelitsas's curator insight, October 13, 2016 5:18 PM
From the symmetry-selective probing of molecular bond orientation with nanometer spatial resolution, the authors determined crystalline phases and orientation in aggregates and films of the organic electronic material perylenetetracarboxylic dianhydride.
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Combining wide-field micro-elastography with Optical Coherence Tomography (OCT)

Combining wide-field micro-elastography with Optical Coherence Tomography (OCT) | Amazing Science |

Incomplete excision of malignant tissue is a major issue in breast-conserving surgery, with typically 20 - 30% of cases requiring a second surgical procedure arising from postoperative detection of an involved margin. A team of scientists and engineers now report advances in the development of a new intraoperative tool, optical coherence micro-elastography, for the assessment of tumor margins on the micro-scale. They demonstrate an important step by conducting whole specimen imaging in intraoperative time frames with a wide-field scanning system acquiring mosaicked elastograms with overall dimensions of ~50 × 50 mm, large enough to image an entire face of most lumpectomy specimens. This capability is enabled by a wide-aperture annular actuator with an internal diameter of 65 mm. The team demonstrates feasibility by presenting elastograms recorded from freshly excised human breast tissue, including from a mastectomy, lumpectomies and a cavity shaving.

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Scientists Watch Bacterial Sensor Respond to Light in Real Time

Scientists Watch Bacterial Sensor Respond to Light in Real Time | Amazing Science |
High-speed X-ray camera reveals ultrafast atomic motions at the root of organisms’ ability to turn light into biological function.


Now, researchers have made a giant leap forward in taking snapshots of these ultrafast reactions in a bacterial light sensor. Using the world’s most powerful X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory, they were able to see atomic motions as fast as 100 quadrillionths of a second – 1,000 times faster than ever before.


Further, “We’re the first to succeed in taking real-time snapshots of an ultrafast structure transition in a protein, in which a molecule excited by light relaxes by rearranging its structure in what is known as trans-to-cis isomerization,” says the study’s principal investigator, Marius Schmidt from the University of Wisconsin, Milwaukee.


The technique could widely benefit studies of light-driven, ultrafast atomic motions. For example, it could reveal:


  • How visual pigments in the human eye respond to light, and how absorbing too much of it damages them.
  • How photosynthetic organisms turn light into chemical energy – a process that could serve as a model for the development of new energy technologies.
  • How atomic structures respond to light pulses of different shape and duration – an important first step toward controlling chemical reactions with light.


“The new data show for the first time how the bacterial sensor reacts immediately after it absorbs light,” says Andy Aquila, a researcher at SLAC’s Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. “The initial response, which is almost instantaneous, is absolutely crucial because it creates a ripple effect in the protein, setting the stage for its biological function. Only LCLS’s X-ray pulses are bright enough and short enough to capture biological processes on this ultrafast timescale.” The results were published today in Science.

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Pathway to ultra-resolution microscopy: Microscopy taps power of programmable DNA

Pathway to ultra-resolution microscopy: Microscopy taps power of programmable DNA | Amazing Science |

Proteins mostly do not work in isolation but rather make up larger complexes like the molecular machines that enable cells to communicate with each other, move cargo around in their interiors or replicate their DNA. Our ability to observe and track each individual protein within these machines is crucial to our ultimate understanding of these processes. Yet, the advent of super-resolution microscopy that has allowed researchers to start visualizing closely positioned molecules or molecular complexes with 10-20 nanometer resolution is not powerful enough to distinguish individual molecular features within those densely packed complexes.


A team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by Core Faculty member Peng Yin, Ph.D., has, for the first time, been able to tell apart features distanced only 5 nanometers from each other in a densely packed, single molecular structure and to achieve the so far highest resolution in optical microscopy. Reported on July 4 in a study in Nature Nanotechnology, the technology, also called "discrete molecular imaging" (DMI), enhances the team’s DNA nanotechnology-powered super-resolution microscopy platform with an integrated set of new imaging methods.


DNA-PAINT technologies, developed by Yin and his team are based on the transient binding of two complementary short DNA strands, one being attached to the molecular target that the researchers aim to visualize and the other attached to a fluorescent dye. Repeated cycles of binding and unbinding create a very defined blinking behavior of the dye at the target site, which is highly programmable by the choice of DNA strands and has now been further exploited by the team’s current work to achieve ultra-high resolution imaging.


"By further harnessing key aspects underlying the blinking conditions in our DNA-PAINT-based technologies and developing a novel method that compensates for tiny but extremely disruptive movements of the microscope stage that carries the samples, we managed to additionally boost the potential beyond what has been possible so far in super-resolution microscopy," said Mingjie Dai, who is the study’s first author and a Graduate Student working with Yin.

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New electron microscope method detects atomic-scale magnetism

New electron microscope method detects atomic-scale magnetism | Amazing Science |

Scientists can now detect magnetic behavior at the atomic level with a new electron microscopy technique developed by a team from the Department of Energy's Oak Ridge National Laboratory and Uppsala University, Sweden. The researchers took a counterintuitive approach by taking advantage of optical distortions that they typically try to eliminate.


"It's a new approach to measure magnetism at the atomic scale," ORNL's Juan Carlos Idrobo said. "We will be able to study materials in a new way. Hard drives, for instance, are made by magnetic domains, and those magnetic domains are about 10 nanometers apart." One nanometer is a billionth of a meter, and the researchers plan to refine their technique to collect magnetic signals from individual atoms that are ten times smaller than a nanometer.

"If we can understand the interaction of those domains with atomic resolution, perhaps in the future we will able to decrease the size of magnetic hard drives," Idrobo said. "We won't know without looking at it."


Researchers have traditionally used scanning transmission electron microscopes to determine where atoms are located within materials. This new technique allows scientists to collect more information about how the atoms behave.


"Magnetism has its origins at the atomic scale, but the techniques that we use to measure it usually have spatial resolutions that are way larger than one atom," Idrobo said. "With an electron microscope, you can make the electron probe as small as possible and if you know how to control the probe, you can pick up a magnetic signature."


The ORNL-Uppsala team developed the technique by rethinking a cornerstone of electron microscopy known as aberration correction. Researchers have spent decades working to eliminate different kinds of aberrations, which are distortions that arise in the electron-optical lens and blur the resulting images.

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Super-resolution microscopy reveals unprecedented detail of immune cells' surface

Super-resolution microscopy reveals unprecedented detail of immune cells' surface | Amazing Science |

When the body is fighting an invading pathogen, white blood cells--including T cells--must respond. Now, Salk Institute researchers have imaged how vital receptors on the surface of T cells bundle together when activated.


This study, the first to visualize this process in lymph nodes, could help scientists better understand how to turn up or down the immune system's activity to treat autoimmune diseases, infections or even cancer. The results were published this week in the Proceedings of the National Academy of Sciences.


"We had seen these receptors cluster and reposition in cultured cells that were artificially stimulated in the lab, but we've never seen their natural arrangements in lymph nodes until now," says senior author Björn Lillemeier, an associate professor in Salk's Nomis Laboratories for Immunobiology and Microbial Pathogenesis, and the Waitt Advanced Biophotonics Center.


T cells are activated when receptors embedded in their outer membrane bind to other immune cells that have digested an antigen, such as a virus, bacteria or cancer cell. In turn, the activated T cells switch on cellular pathways that help the body both actively seek out and destroy the antigen and remember it for the future. In the past, by looking at T-cell receptors embedded in isolated cells under the microscope, researchers discovered that the receptors are arranged in clusters--called protein islands--that merge when the cells are activated.


Lillemeier wanted more detail on how the receptors are arranged in tissue and how that arrangement might change when the T cells are activated in living hosts. The team used a super-resolution microscope developed in the laboratory of co-senior author Hu Cang, assistant professor at Salk's Waitt Advanced Biophotonics Center and holder of the Frederick B. Rentschler Developmental Chair. This microscopy approach, called light-sheet direct stochastic optical reconstruction microscopy (dSTORM), let the researchers watch T cell receptors in the membranes of T cells in mouse lymph nodes at a resolution of approximately 50 nanometers.


The new imagery confirmed the previous observation that protein islands of T-cell receptors merge into larger "microclusters" when T cells are activated. But it also showed that, before cells are activated, the protein islands are already arranged in groups--dubbed "territories" by Lillemeier's team. "The pre-organization on the molecular level basically turns the T cell into a loaded gun," says Lillemeier.

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Cooperating High-Precision Robots Manipulate Microparticles under Microscope

Cooperating High-Precision Robots Manipulate Microparticles under Microscope | Amazing Science |

The robotic manipulation of biological samples that are measured in microns is a challenging task, requiring high precision and dexterity. The end-effectors and the manipulators must be as flexible as possible to manage the variations in the size and shape of the samples, while at the same time protecting them from any form of damage (e.g. perforation).


This article discusses the work conducted at the Hamlyn Center for Robotic Surgery of Imperial College London to tackle these challenges. The manipulation tasks were semi-automated by developing a multi-robots cooperation and a compliant end-effector. This solution can be applied to cell measurements, single cell surgery, tissue engineering and cell enucleation.

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A new technique for super-resolution digital microscopy using lens-free holograms

A new technique for super-resolution digital microscopy using lens-free holograms | Amazing Science |

Researchers from the California NanoSystems Institute at UCLA have created a new technique using lens-free holograms that greatly enhances digital microscopy images, which are sometimes blurry and pixelated.

The new technique, called “wavelength scanning pixel super-resolution,” uses a device that captures a stack of digital images of the same specimen, each with a slightly different wavelength of light. Then, researchers apply a newly devised algorithm that divides the pixels in each captured image into a number of smaller pixels, resulting in a much higher-resolution digital image of the specimen.

The research team was led by Aydogan Ozcan, Chancellor’s Professor of Electrical Engineering and Bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science. The study appears in an open-access paper in the journal Light: Science and Applications, published by the Nature Publishing Group.

“These results mean we can see and inspect large samples with finer details at the sub-micron [nanoscale] level,” Ozcan said. “We have applied this method to lens-based conventional microscopes, as well as our lensless on-chip microscopy systems that create microscopic images using holograms, and it works across all these platforms.”

The benefits of this new method are wide-ranging, but especially significant in pathology, where rapid microscopic imaging of large numbers of tissue or blood cells is key to diagnosing diseases such as cancer. The specimens used in the study were blood samples, used to screen for various diseases, and Papanicolaou tests, which are used to screen for cervical cancer.

Ozcan said that wavelength scanning super-resolution works on both colorless and dye-stained samples. The entire apparatus fits on a desktop, so its size and convenience could be of great benefit to doctors and scientists using microscopes in resource-limited settings such as clinics in developing countries.

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Guts of giant mimivirus imaged in 3D brings X-ray laser images of live cells one step closer

Guts of giant mimivirus imaged in 3D brings X-ray laser images of live cells one step closer | Amazing Science |

What looks like a blurry, misshapen flower is actually the innards of one of the world's largest viruses, imaged in three dimensions using powerful X-rays. The same technique could one day create three-dimensional (3D) snapshots of individual molecules, and perhaps even of live bacteria.

The mimivirus (Acanthamoeba polyphaga mimivirus; shown rotating above) carries DNA inside an icosahedral (20-faced) outer shell, and is nearly as large as a typical bacterium. Researchers used the Linac Coherent Light Source (LCLS) at the SLAC National Accelerator Laboratory in Menlo Park, California, to fire powerful X-rays at a single virus particle and build up the 125-nanometre-resolution picture of its internal electron density.

The scans — which are published on 2 March in Physical Review Letters1 — are a proof of principle that extremely powerful X-ray beams could one day take pictures of small objects that cannot be crystallized, says Janos Hajdu, a molecular biophysicist at Uppsala University in Sweden.

Structural biologists routinely fire beams of X-rays at complex molecules and viruses to decode their shapes. But a single molecule does not scatter sufficient X-rays to allow its shape to be reconstructed. In X-ray crystallography, the problem is solved by arranging many copies of the same object into a crystal and looking at repeating patterns in the scattered light. But some molecules are hard to crystallize. And larger, more-complex objects tend to differ from one specimen to the next — for example, genetic material is not arranged in the same way inside all living cells of the same bacterium strain.

The solution could lie in machines known as free-electron lasers, which produce short, densely-packed pulses of X-rays. Each pulse packs in so many high-energy X-ray photons that the machines can — in theory — produce pictures even of single molecules. The LCLS was the first of a handful of such facilities that now exist around the world.

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New nonlinear SIM microscope gives deepest view yet of living cells

New nonlinear SIM microscope gives deepest view yet of living cells | Amazing Science |

Two new microscopy techniques are helping scientists see smaller structures in living cells than ever glimpsed before.

Scientists can now view structures just 45 to 84 nanometers wide, Nobel prize-winning physicist Eric Betzig of the Howard Hughes Medical Research Institute’sJanelia research campus in Ashburn, Va., and colleaguesreport in the Aug. 28 Science. The techniques beat the previous resolution of 100 nanometers and shatters the 250 nanometer “diffraction barrier,” imposed by the bending of light.

Using other tricks to improve the super-resolution methods also allowed the researchers to take ultraquick pictures with less cell-damaging light than before. As a result, scientists can watch sub-second interactions within cells, revealing new insights into how cells work.

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