Thursday, July 24, 2008
Neuron Membrane Model to Study Alzheimer's
NIST scientists have built a model of the membrane that surrounds neurons in the brain, a tool which should help to discover the mechanisms behind Alzheimer's onset.
The brain’s neurons transmit nerve impulses down a long stem that is surrounded by a two-layer membrane. In the neuron’s normal, “rest” state, this membrane actively sorts sodium ions to the outside of the cell and potassium ions to the inside. To transmit a nerve impulse, an electrochemical change ripples down the membrane in advance of the impulse, making it temporarily more permeable and allowing the ions to swap places. That in turn changes the electrical potential across the membrane, allowing the impulse to pass. Afterwards, the membrane returns to rest and begins sorting the ions again.Medical experts have hypothesized for years that small polypeptides called amyloid beta peptides somehow create a “leaky” membrane that disrupts this balanced back-and-forth switching of the electrical potential and, in turn, normal impulse transmission. Alzheimer’s disease—the progressive brain disorder that is the nation’s sixth leading cause of death—is believed to start with such breakdowns. As the disease progresses, amyloid beta peptides clump together to form plaques that further destroy nerve function.
Studying the beginnings of Alzheimer’s is nearly impossible in humans because by the time the disease is diagnosed, most patients have moved into its later stages. Researchers at NIST have developed a laboratory model that recreates a simplified version of the nerve cell membrane, allowing the study of Alzheimer’s disease mechanisms at the molecular level. A clever piece of molecular-level design, the system is built by first covering a silica surface with gold. Sulfur atoms, which bond well to gold, are then added to act as anchors to hold the bilayer membrane. The result is a stable, tethered membrane with an aqueous environment on both sides that accurately models the behavior of the nerve cell membrane.
A collaborative team of researchers from NIST, Carnegie Mellon University, the University of California-Irvine and the Biochemistry Institute (BCHI) in Vilnius, Lithuania, exposed the membrane model to different concentrations of a specific form of amyloid beta peptides comprised of soluble, tiny (5-6 nanometers, approximately twice the diameter of a DNA helix) chains. The researchers found increased cation movement across the normally strong barrier at the higher concentrations of the peptides. The data support the hypothesis that membrane “leakiness” is not due to a permanent hole being formed but rather to an aggregation of amyloid beta peptides in the membrane that allows cations to be passed from peptide to peptide across the bilayer, like a baton handed off by relay runners.
Press release: NIST Membrane Model May Unlock Secrets of Early-Stage Alzheimer's
Image: Diagram of NIST's “tethered bilayer membrane” model shows the silica surface covered with gold at the bottom. Sulfur atoms (yellow spheres) bind to the gold and act as anchors for the tethers, chains of atoms extending up to the lipid bilayer membrane at the top of the structure. Credit: NIST
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Tuesday, July 22, 2008
Innocent Dating, or Eugenics for 21st Century?
Actually, it's all pretty innocent. A Swiss company called GenePartner has launched its dating service designed to match men and women based on the correlation of genes that express the HLA (human leukocyte antigen) molecules. And why? Well, there is evidence that people tend to choose a partner on the basis of their HLA-dependent odortype. (Matching of HLA antigens is also important for organ transplantation.)
More about the concept behind the service:
The GenePartner project was inspired by a famous study performed by Prof. Dr. Wedekind at the University of Bern in Switzerland. In this study, Prof. Dr. Wedekind recruited female volunteers to smell T-shirts worn by men for three consecutive days and rate them for attractiveness. He then analyzed the particular part of DNA that codes for HLA (human leukocyte antigen) molecules and found that women preferred T-shirts from men whose HLA molecules were most different from their own. Sensing and classifying the HLA genes is something our bodies do automatically and subconsciously.HLA molecules play a central role in controlling the activation of immunological effectors during an immune response and are therefore essential for immune resistance. A greater variety in HLA genes offers a greater variety in possible immune responses. In terms of evolution, this makes perfect sense: children of couples with a higher variety in their HLA genes (and hence, immune responses) will have better protection from a greater variety of diseases. Simply put, this means that their body has more weapons to use in its defence against a disease. An important additional effect is that comparing HLA genes can help identify kinship and prevent potential inbreeding.
In 2003, the GenePartner team decided to take this discovery one step further and see if there are specific patterns of HLA genes that "attract" each other more. In collaboration with the Swiss Institute for Behavioural Genetics, we tested a large number of individuals (both romantically involved couples and persons not in a relationship) for their HLA genes. The results were astounding and led to the development of a formula that combines the diversity factor studied by Prof. Dr. Wedekind, together with several other evolutionary factors researched and developed by the Swiss Institute for Behavioral Genetics.
The GenePartner formula measures the genetic compatibility between two individuals and makes an accurate prediction of the strength of their basis for a long-lasting and fulfilling romantic relationship.
Hat tip: ScienceRoll!
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Monday, July 21, 2008
Mouse Spinal Cord Gene Map Goes Online
The Allen Institute for Brain Science is making publicly available its genome-wide map of expressions of spinal cord genes.
From the institute:
Since mice and humans share 90 percent of genes, and the mouse is a well-established model for the study of human diseases, the Allen Spinal Cord Atlas will provide scientists and physicians with an expanded foundation of knowledge to discover new treatments for numerous diseases and disorders. The Allen Spinal Cord Atlas will utilize the same concept and technology as the Institute’s inaugural Allen Brain Atlas.From start to finish, the Allen Spinal Cord Atlas will be completed within a swift, twelve-month timeframe. While inaugural data—approximately 2,000 genes—from the Allen Spinal Cord Atlas is now available, the Institute will continue to follow its founding mission and upload additional information until the projected completion in early 2009. It is estimated that hundreds of users from universities, research institutes, pharmaceutical companies and government organizations will use the atlas.
When completed, the Allen Spinal Cord Atlas will detail approximately 20,000 genes including data from youth and adult developmental stages. It will also feature data across the full length of the spinal cord as well as anatomical reference sections.
Press release: ALLEN INSTITUTE FOR BRAIN SCIENCE UNVEILS WORLD'S FIRST GENOME-WIDE SPINAL CORD ATLAS (PDF)
Image: Slide cartridges from the Allen Spinal Cord Atlas being sorted.
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Friday, July 18, 2008
The Ergopip: Pipette Remixed
We are not terribly sure that this newly designed pipette adds any more grandeur to the institution where it is coming from, the University of Cambridge. However, it does seem to offer a more convenient way for those in labs to go though routines.
From the Department of Engineering at the University of Cambridge:
While current models satisfy the need for precision and reliability, their design falls a long way short in terms of ease of use. They are entirely thumb-operated and are known to cause cases of repetitive strain injury. The students have designed a comfortable, easy-to-use pipette, the Ergopip, which distributes workload to the user's fingers and is just as precise and reliable as existing versions.
Full story from The Engineer Online: Students design better pipette...
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Tuesday, July 15, 2008
MarrowXpress Gets Green Light in US
A month ago we reported that the EU has given approval to ThermoGenesis Corp. (Rancho Cordova, CA) to market the company's MarrowXpress device, which isolates and concentrates stem cells from bone marrow aspirate. Today's news is that the FDA has classified the device as a piece of laboratory equipment for medical use, and approved it for sale in the US.
From ThermoGenesis:
Last month, the Company announced it had submitted a 510(k) pre-market notification application to the FDA. Upon its review, the FDA determined that the device was exempt from the agency’s pre-market notification requirements and will instead be regulated as laboratory equipment labeled for a specific medical use. The device is a derivative of the Company’s AutoXpress™ (AXP™) Platform that is used to volume reduce and collect stem cells from umbilical cord blood.“This notification that we can immediately begin marketing our MXP device is a major regulatory milestone for the Company and particularly exciting since we received this notification just several weeks after filing our submission, and since it follows by less than a month from having received the CE-Mark enabling us to market the device in the European Community,” noted Dr. William Osgood, Chief Executive Officer.
Press release: THERMOGENESIS ANNOUNCES FDA AUTHORIZATION TO MARKET MARROWXPRESS™ (MXP™) (PDF)
Product page: MarrowXpress...
Flashback: MarrowXpress Stem Cell Processing System Gets CE Mark
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Wednesday, July 2, 2008
Novel Molecular Probes Detect Protein-Protein Interaction
Investigators from MIT are reporting in the online June 27 issue of J. Am. Chem. Soc. a new method to tag intracellular (or in vitro) proteins to allow the study of their interactions.
Here's what the authors note in the study:
One protein partner is fused to Escherichia coli biotin ligase (BirA), while the other protein partner is fused to BirA’s “acceptor peptide” (AP) substrate. If the two proteins interact, BirA will catalyze site-specific biotinylation of AP, which can be detected by streptavidin staining. To minimize nonspecific signals, we engineered the AP sequence to reduce its intrinsic affinity for BirA. The rapamycin-controlled interaction between FKBP and FRB proteins could be detected in vitro and in cells with a signal to background ratio as high as 28. We also extended the method to imaging of the phosphorylation-dependent interaction between Cdc25C phosphatase and 14-3-3ε phosphoserine/threonine binding protein. Protein−protein interaction detection by proximity biotinylation has the advantages of low background, high sensitivity, small AP tag size, and good spatial resolution in cells.
The following is from a statement issued by MIT:
The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.
Their work is conceptually related to an approach that uses GFPs (green fluorescent proteins), which glow when activated, as probes. Half of each GFP molecule is attached to the proteins of interest, and when the proteins interact, the GFP halves fuse and glow. However, this technique results in many false positives, because the GFP halves seek each other out and bind even when the proteins they are attached to are not interacting, said Ting.
The new probes could be used to study nearly any protein-protein interaction, Ting [Alice Ting, MIT Pfizer-Laubach Career Development Assistant Professor of Chemistry] said. The researchers tested their probes on two signaling proteins involved in suppression of the immune system, and on two proteins that play a role in cell division. They are currently using the probe to image the interaction of proteins involved in synapse growth in live neurons.
Press release: New probe may help untangle cells' signaling pathways ...
Abstract: Protein-Protein Interaction Detection in Vitro and in Cells by Proximity Biotinylation J. Am. Chem. Soc., ASAP Article, 10.1021/ja801445p
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Monday, June 30, 2008
BioTime Begins First Complete Database of Human Stem Cell Differentiations
BioTime Inc of Emeryville, California, a daughter company of Embryome Sciences, has launched an online database that aims to document and map all the different cells that were lab created out of human embryonic stem cells.
From the announcement:
In a paper published today [June 27, 2008] titled "The International Embryome Initiative: A Collaborative Database for Navigating the Complexities of Human Embryonic Stem Cell Differentiation," available online at www.futuremedicine.com/loi/rme, BioTime and Embryome Sciences describe the collaboration to map the "embryome" in a manner similar to the international initiatives to map the human DNA or genome in the 1990s. While the database launched today at Embryome.com is currently populated with nearly 2,000 distinct cell types, the complete map will require the collective efforts of hundreds of scientists over the coming months.The California Institute for Regenerative Medicine, which is the funding arm of the $3 billion California stem cell initiative, has agreed to be the first subscriber to all features of the database on behalf of all researchers residing within the state of California.
Press release: BioTime, Inc. and Embryome Sciences, Inc. Launch Embryome.com and the International Embryome Initiative ...
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Zinc Finger DNA-Binding Protein Technology Gives T-Cells Shield Against HIV
Sangamo BioSciences, Inc., based in Richmond, California, is reporting positive news showing that CD4 T-cells can be made HIV resistant with the help of the company's proprietary zinc finger DNA-binding protein nucleases (ZFN), specially developed transcription factors.
From Sangamo:
Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. Individuals carrying a naturally occurring mutation of their CCR5 gene, a variant known as CCR5-delta32, have been shown to be resistant to HIV infection."The data described in this paper are an important demonstration of the potential therapeutic properties of our product," commented Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "We have demonstrated that a single treatment with our CCR5-specific ZFNs generates a population of HIV-resistant human T-cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation. ZFN-modification of these cells is permanent and makes them resistant to HIV. The modified cells preferentially survive and expand in an animal after HIV infection, providing a reservoir of healthy and uninfectable immune cells. Furthermore, we observed that animals given the ZFN-modified cells had increased numbers of CD4 cells and substantially lower levels of HIV in their blood compared to animals given non-modified cells demonstrating statistically significant protection from the virus. In an HIV-infected patient, such modified cells could be available as a protected reservoir within the immune system to fight both opportunistic infections and HIV itself."
Several major pharmaceutical companies have initiated programs to develop small molecule or monoclonal antibody approaches to block the binding of HIV to CCR5. However, a small molecule or antibody approach requires the constant presence of a sufficiently high concentration of these drugs or antibody to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell and other tissues in the body. One such drug has been approved by the US Food and Drug Administration with a "black box" warning, the strongest for prescription drugs, concerning the risk of liver toxicity and the possibility of heart attacks.
Sangamo's ZFN technology represents a means of potentially circumventing these limitations or risks by specifically modifying only CD4 T-cells, the principal target of HIV pathology, in a one-time exposure of the cells to ZFNs. This results in permanent modification of the CCR5 protein such that HIV cannot enter and infect the cells. This approach could potentially enable the generation of a reservoir of protected CD4 T-cells that are available to fight the opportunistic infections that are characteristic of AIDS as well as HIV itself. Sangamo expects to initiate a clinical trial to evaluate this approach by the end of the year.
Sangamo ZFP technology page...
Abstract in Nature: Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
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Tuesday, June 24, 2008
Genetic Silencing Technology Improves With Help From Quantum Dots
At the University of Washington and Emory University, scientists have developed a new technique that allows for faster selective silencing of particular genes. At the heart of the method, which is designed for selective regulation of protein production, are specially engineered multifunctional nanoparticles composed of short-interfering RNA (siRNA) and semiconductor quantum dots (QDs), all enclosed by a proton-absorbing polymeric coating (aka proton sponge).
Each quantum dot was surrounded by a proton sponge that carried a positive charge. Without any quantum dots attached, the siRNA's negative charge would prevent it from penetrating a cell's wall. With the quantum-dot chaperone, the more weakly charged siRNA complex crosses the cellular wall, escapes from the endosome (a fatty bubble that surrounds incoming material) and accumulates in the cellular fluid, where it can do its work disrupting protein manufacture.Key to the newly published approach is that researchers can adjust the chemical makeup of the quantum dot's proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the siRNA.
Quantum dots were dramatically better than existing techniques at stopping gene activity. In experiments, a cell's production of a test protein dropped to 2 percent when siRNA was delivered with quantum dots. By contrast, the test protein was produced at 13 percent to 51 percent of normal levels when the siRNA was delivered with one of three commercial reagents, or reaction-causing substances, now commonly used in laboratories.
Central to the finding is that fluorescent quantum dots allow scientists to watch the siRNA's movements. Previous siRNA trackers gave off light for less than a minute, while quantum dots, developed for imaging, emit light for hours at a time. In the experiments the authors were able to watch the process for many hours to track the gene-silencer's path.
The new approach is also five to 10 times less toxic to the cell than existing chemicals, meaning the quantum dot chaperones are less likely to harm cells. The ideal delivery vehicle would have no effect; the only biological change would be siRNA blocking cells' production of an unwanted protein.
The exact reason that the quantum dots were more effective than previous techniques is, however, still a mystery.
University of Washington press release: Gene silencer and quantum dots reduce protein production to a whisper ...
Abstract: Proton-Sponge Coated Quantum Dots for siRNA Delivery and Intracellular Imaging J. Am. Chem. Soc., ASAP Article, 10.1021/ja800086u
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Friday, June 20, 2008
OMX, World's Highest Resolution Wide-field Light Microscope Goes Live
An interdisciplinary group of researchers at UC Davis and UCSF, in collaboration with the Issaquah, WA based Applied Precision, Inc, built the world's first commercial OMX (Optical Microscopy eXperimental) microscope, a device designed to provide hitherto unprecedented level of resolution with visible spectrum light. According to a statement by UC Davis, this technology is not only twice as powerful as the best conventional light microscope, but it also has potential for a 10-fold improvement, possibly "allowing the imaging of small structures within cells." Furthermore, the microscope "can also produce rapid three-dimensional images of live samples in real time to study cellular processes in action."
The OMX is based on two main imaging modalities: Structured Illumination and Fast Live 3d Imaging. Here's the explanation from the project page at UCSF:
1) Structured IlluminationStructured illumination microscopy involves illuminating the sample with a pattern caused by interfering beams of light, rather than a single uniform beam. OMX achieves this illumination by passing incident light through a diffraction grating, then recombining the diffracted beams in the sample plane. The emitted light from a sample so illuminated contains normally unobservable high-resolution information that has been shifted into the observable region of frequency space. By acquiring several images of shifted patterns at each Z section, the high-resolution information can be separated and computationally re-shifted to its correct position in frequency space, leading to an overall increase in the resolution of the final reconstructed image.
2) Fast Live 3d Imaging
Although fixed images are a very useful source of information, live imaging is becoming more and more important. Live imaging allows dynamic processes to be directly observed. There are many challenges in live imaging, including bleaching of fluorophores, imaging through tissues, and keeping the sample alive. Images must be acquired quickly, not only so that the process of interest is accurately sampled, but also so that the individual planes of a three-dimensional picture comprise a single timepoint; i.e., temporal spreading of a single image must be minimized. To meet these challenges OMX was designed with very fast cameras and shutters capable of acquiring 100 images per second, a piezoelectric stage that can move very quickly while images are being acquired, and a digital signal processor (DSP) controlling all aspects of image acquisition to ensure precise timing. OMX can acquire separate wavelengths from 4 cameras simultaneously, allowing multiple signals to be detected. Ratio imaging and FRET can also be performed.
More reads: UC Davis press release: New Microscope Is First of Its Kind...;
Applied Precision press release: The World's Most Powerful Commercial Wide-Field Light Microscope Installed at the UC Davis Center for Biophotonics Science and Technology...
OMX project pages at UC Davis and UCSF
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Thursday, June 19, 2008
MarrowXpress Stem Cell Processing System Gets CE Mark
ThermoGenesis received CE Mark clearance for their MarrowXpress stem cell processing device today. It is still pending 510(k) clearance, so it looks like the US will have to wait for European labs to try their luck.
The device automatically isolates and concentrates stem cells from bone marrow aspirate in 30 minutes. The entire system runs on a rechargeable NiMH battery. It also includes data tracking software that communicates with the device in real-time. Currently it is only intended for research purposes.
Product page: MarrowXpress...
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Friday, June 13, 2008
X-Ray Linear Accelerator, A New Ultra-Microscope Into Life
Cornell University, thanks to a major grant from the NSF, is moving forward on building an ultra powerful, ultra fast x-ray machine that promises to capture biomolecular processes happening in full motion video. Using technology developed at the university, called energy-recovery linac (ERL), the plan is to build a mile long linear accelerator on which multiple research projects can operate at the same time.
From the press release:
Moving beyond traditional X-ray crystallography systems--where the arrangement of atoms in crystalline material is revealed by analyzing the way X-ray beams are scattered from electrons in the crystal--the energy-recovery linac offers significant advantages. For one, materials subjected to ultrabright X-ray pulses need not be in crystalline form. And the tightly focused beam allows studies at much smaller scales.As envisioned and invented by experimental physicists at Cornell, energy-recovery linear accelerators produce high-energy, pulsed X-ray beams by injecting electrons into the electromagnetic fields of a series of superconducting microwave cavities in a linear accelerator. Then, in a return loop, the electron beam is turned into X-rays by passing through undulators, which force the beam to oscillate to the right and left of its mean path with horseshoe magnets of alternating orientations. The pulsed X-rays are now ready for studies in multiple stations at the facility.
While the ERL X-ray beam loses about 0.04 percent of its energy during oscillation, 99.98 percent of its remaining energy is recaptured into the electromagnetic fields when the electrons are re-injected into the linac for deceleration--providing energy to accelerate subsequent bunches of electrons.
Compared to a traditional storage-ring X-ray source, such as CHESS, which recycles electrons billions of times but suffers from a compromised beam size, ERLs send each bunch of electrons through the undulators only once. Again and again, ERLs recover and reuse energy that accelerates electron bunches, while maintaining very small beam size--the key to the brilliance needed to study intimate details at the nano-scale.
Full story: Brightest X-ray Vision at the Nano-scale...
Video of Joel Brock of Cornell University, explaining the workings and hopes for the new project.
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Thursday, June 12, 2008
A Single Cell Pedometer Developed
Scientists at Fraunhofer Institute for Applied Optics and Precision Engineering have developed an optical sensor that can quantify the force that a cell exerts on a special surface as it moves across it, which should allow for creating somatic cell sorting machines and single cell diagnostic devices. The project is a part of the European Information Society Technologies initiative.
It consists of a smooth surface that is studded with 250,000 tiny plastic columns measuring only five microns in diameter, rather like a fakir’s bed of nails. These columns are made of elastic polyurethane plastic. When a cell glides across them, it bends them very slightly sideways. This deflection is registered by a digital camera and analyzed by a special software program. The researchers working with project manager Dr. Norbert Danz of the Fraunhofer Institute for Applied Optics and Precision Engineering IOF in Jena have already shown that their ‘Cellforce’ sensor works. It will be the task of initial biological tests to show how different cell types behave. “Analysis of cell locomotion is important for numerous applications,” says Danz. “It could be used to check whether bone cells are successfully populating an implant, or how well a wound is healing.”Developing the sensor was no easy undertaking. For one thing, the columns have to be coated in such a way that living cells are happy to move across their tips. The cells would otherwise avoid the tips and continue their journey lower down between the columns. In that case, there would be no deflection at all. Danz had the task of adapting the microscope required for cell magnification to make it exactly right for the application. Building the delicate column structure developed by researchers at the Fraunhofer Institute for Manufacturing Engineering and Applied Materials Research IFAM in Bremen is no less tricky: The researchers press liquid plastic at a pressure of 2000 bar into a negative mold and allow it to harden. It is a challenge even to manufacture the required mold, with its 250,000 micron-sized holes. To allow cost-effective production of the ‘Cellforce’ sensor in future, the researchers utilize commercially available plastics and well-established techniques from chip manufacture. The first ‘Cellforce’ prototype is expected to be ready in a year’s time.
Press release: Measuring the footprint of cells ...
Project info page: Development of a single cell based biosensor for subcellular on-line monitoring of cell performance for diagnosis and healthcare...
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Monday, May 19, 2008
DNA Sequencing Through Imaging of Base Pairs
MIT Technology Review has brought to our attention ZS Genetics, a North Reading, MA company that is developing a surprisingly new method of sequencing DNA. Instead of using common bio-chemical methods like PCR, the company is using electron microscopy to effectively image the sequence of DNA molecule's base pairs. As the company proclaims, they "work at the scale of life."
More about the technology, taken from the company's website:
Normal DNA is not visible with electron microscopes (EMs). ZSG has a simple process that makes DNA directly and starkly visible.Light elements are transparent to Electron Microscopes (EMs). EMs generate contrast from the charges on atomic nuclei. Atoms with low Z are transparent to EMs; atoms with high Z are opaque. The average Z for DNA is around 5.5. The structure of a double strand means that more than half of the cross-section is simply void under EM vacuum conditions, giving an effective average Z of about 2.0. Consequently, natural DNA is essentially invisible to EM analysis.
Normal DNA has only light elements, so it is inherently low contrast. Atomic numbers (Zs) for naturally occurring elements range from 1 to 92. DNA is mostly made of Carbon, Nitrogen, and Oxygen which have Z's of 6, 7, & 8 respectively. There are also small amounts of Hydrogen and Phosphorus with Z's of 1 & 15.
ZSG uses heavier elements as labels. Iodated (Z = 53) and Brominated (Z = 35) nucleotides are commercially available. We can use any element, or a combination of elements, with sufficient nuclear charge (Z) to provide an adequate ratio of signal-to-background noise. The specific types of atom(s) we use and the number of base-types labeled depends on the product and application.
Labels of a few or one atom are more precise than fluorescent labels. They are incorporated into the DNA in much the same way as fluorescent labels but are dramatically smaller and consequently easier to incorporate into very long molecules. Atomic label bias should be less than fluorescent labels and also result in greater experiment reproducibility.
Product page: ZS Genetics technology...
More from MIT Technology Review...
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Friday, May 16, 2008
Probing Protein-Membrane Interaction by Single Plasmonic Nanoparticles
Michael Berger over at Nanowerk has filed a report about a novel nanoscale sensor platform developed by investigators at the Institute of Physical Chemistry, University of Mainz in Germany. The most exciting thing for us about the platform, which is built upon membrane coated plasmonic particles, is in its ability to offer a local analysis of protein interaction with biological membranes, or as explained in the article, these nanoparticles "can serve as reporters for cellular reactions taking place on and within biological membranes."
Read: Probing biomolecular interactions with single plasmonic nanoparticles...
Abstract: Protein--Membrane Interaction Probed by Single Plasmonic Nanoparticles ASAP Nano Lett., ASAP Article, 10.1021/nl080805l
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Leica Introduces New Stereomicroscopes M205 FA and M165 FC
Leica Microsystems has introduced two new stereomicroscopes, Leica M205 FA (top) and M165 FC (below). The devices are based on the company's innovative FusionOptic™ technology that utilizes normal human neurology to increase the resolution of stereomicroscopes (for details, see our Nov. 2007 post:FusionOptic™ technology).
German Healthcare Export Group provides the details:
The Leica M205 FA and M165 FC stereomicroscopes are Leica Microsystems‘ latest addition to its innovative M series for demanding fluorescence applications in developmental, molecular and cellular biology.Combining the revolutionary FusionOptics™ technology with the successful TripleBeam™ principle, the fully automated Leica M205 FA creates fluorescence images of exceptional quality. Used for the first time in the M series, FusionOptics™ (patent pending) takes advantage of a neurological phenomenon: The left beam path produces great depth of field, while the right beam path provides a high-resolution image.
The human brain itself then combines the best information from both channels, using it to compose an image whose resolution and depth of field have never been achieved in any stereomicroscope before.
With its fully apochromatic optics, the largest zoom range on the market (20.5:1) and the top resolution performance of up to 1050 lp/mm, the Leica M205 FA is able to show the viewer details that used to be invisible.The TripleBeam™ principle, with its patented third beam path reserved exclusively for fluorescence illumination, delivers evenly illuminated, reflex-free fields of view at all zoom settings. Besides this, the FluoCombi III™ objective revolver features the unique capability to exploit all the advantages of both stereo and high-resolution micro-objectives on one instrument with a simple switch. It enables parallaxfree imaging from overview magnification to the finest detail. Time-intensive studies of living organisms and documentation of complex images series and multifluorescence images are made possible and instantly reproducible by motorizing focus, zoom, filter changer, iris diaphragm fluorescence intensity manager and microscope stage.
An external SmartTouchTM control unit ensures convenient control of all microscope functions using a clearly arranged touch display and freely programmable control buttons. The microscope is fully integrated in the modular software solutions Leica AF6000 E to AF6000. For documentation, image overlay and time series, the Leica AF6000 E is recommended as an introductory software package. This can be upgraded to the Leica AF6000 as necessary to suit applications ranging from multi-channel fluorescence, time and z series with parallax correction to 3D reconstruction.
The Leica M165 FC continues the tradition of high-quality manual fluorescence stereomicroscopes. With this microscope, the classical stereo-optics approach has been exploited to the utmost optical limits. The fully apochromatically corrected 16.5:1 zoom – combined with TripleBeam™ and FluoCombi III™ – guarantees high-contrast fluorescence images down to the finest structures of the specimen. Encoded zoom, iris diaphragm and objective revolver allow configuration parameters and optical data to be reproducibly read out at the computer.
Product pages: Leica M205 FA and Leica M165 FC
German Healthcare Export Group: Leica Microsystems Combines FusionOpticsTM with TripleBeamTM...
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Friday, April 25, 2008
Scientists Create Cardiac Cells From Stem Cells
Scientists from the McEwen Centre for Regenerative Medicine at the University of Toronto created mesoderm heart progenitor cells from embryonic stem cells. Such a progenitor line is responsible for the production of three main types of cardiac cells: cardiomyocytes, endothelial cells and vascular smooth muscle cells.
From the press release by McEwen Centre:
Canadian scientist, Dr. Gordon Keller, and his team of international researchers have successfully grown human heart progenitor cells from embryonic stem cells. With this advancement, Dr. Keller, director of Toronto’s McEwen Centre for Regenerative Medicine at the University Health Network, and his team, have taken a significant step towards the creation of functioning heart tissue.“This development means that we can efficiently and accurately make different types of human heart cells for use in both basic and clinical research, says Dr. Keller. “The immediate impact of this is significant as we now have an unlimited supply of these cells to study how they develop, how they function and how they respond to different drugs. In the future, these cells may also be very effective in developing new strategies for repairing damaged hearts, following a heart attack.”
The study, a medical first, details supplying embryonic stem cell cultures with a series of factors that direct them to develop into immature heart cells, known as heart progenitor cells. These progenitors are able to make three major cell types found in the human heart - cardiomyocytes, endothelial cells and vascular smooth muscle cells. These three cell types are integral to the healthy function of the human heart.
More from Nature: Beating heart tissue grown in lab...
Abstract: Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population... doi:10.1038/nature06894
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Tuesday, April 22, 2008
The $100 Genome
The MIT Technology Review features an article on current work by Complete Genomics out of Mountain View, CA and BioNanomatrix of Philadelphia, that try to develop a method to sequence the human genome for about $100, a serious drop from the current cheapest $60,000 method.
Most existing technologies detect the sequence of DNA a single letter at a time. But Complete Genomics aims to speed the process by detecting entire "words," each composed of five DNA letters. Drmanac likens the technology to Google searches, which query a database of text with keywords. Further speeding up the process with novel chemistry and advances in nanofabrication, the companies will develop a device that can simultaneously read the sequence of multiple genomes on a single chip.To accomplish the new sequencing, scientists first generate all possible combinations of five-letter DNA segments, given the four letters, or bases, that make up all DNA. These segments are labeled with different types of fluorescent markers and added in groups to a single-stranded molecule of DNA. When a particular segment matches a sequence on the strand of DNA to be read, it binds to that part of the molecule. A specialized camera then snaps a picture--the different fluorescent signals indicate the sequence at specific points along the strand of DNA. The process is repeated with different five-letter DNA combinations, until the entire chromosome is sequenced. The approach is feasible because of the recent availability of cheap DNA synthesis, making it much more efficient to generate libraries of these DNA segments.
Each DNA molecule will be threaded into a nanofluidics device, made by Philadelphia-based BioNanomatrix, lined with rows of tiny channels. The narrow width of the channels--about 100 nanometers--forces the normally tangled DNA to unwind, lining up like a train in a long tunnel and giving researchers a clear view of the molecule. "Since we can stretch out DNA, we can get a huge amount of information from each piece of DNA we look at," says Mike Boyce-Jacino, chief executive officer of BioNanomatrix. "The big difference from any other approach is that we are looking at physical location at the same time we are looking at sequence information." Sequencing methods currently in use sequence small fragments of DNA and then piece together the location of each fragment computationally, which is more time consuming and requires repetitive sequencing.
Full post at MIT Tech Review...
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Friday, April 18, 2008
Single Cell Tweezers Developed
Researchers at the University of Toronto created a pair of tweezers capable of picking up, without causing damage, individual cells, using a force of as little as 20 nanoNewtons.
At their most sensitive, they exert only enough force to support 2 millionths of a gram against the pull of gravity.The tweezers' arms are about 3 millimetres long, with fine tips able to grasp cells just 10 micrometres across. In trials using pig heart cells, the pincer could pick up and move the cells without damaging them. Holding them with only 100 nanoNewtons of force, the gripper squashed the cells out of shape by only 15%.
The grippers are controlled by software that can identify individual cells and move the tweezers into position in just a few seconds.
More at the NewScientist.com...
(hat tip: Engadget)