Posts tagged tissue
Articles and news from the latest research reports.
DNA Modifications Measured in Blood Signal Related Changes in the Brain
Research linked to stress in mice confirms blood-brain comparison is valid
Johns Hopkins researchers say they have confirmed suspicions that DNA modifications found in the blood of mice exposed to high levels of stress hormone — and showing signs of anxiety — are directly related to changes found in their brain tissues.
The proof-of-concept study, reported online ahead of print in the June issue of Psychoneuroendocrinology, offers what the research team calls the first evidence that epigenetic changes that alter the way genes function without changing their underlying DNA sequence — and are detectable in blood — mirror alterations in brain tissue linked to underlying psychiatric diseases.
The new study reports only on so-called epigenetic changes to a single stress response gene called FKBP5, which has been implicated in depression, bipolar disorder and post-traumatic stress disorder. But the researchers say they have discovered the same blood and brain matches in dozens more genes, which regulate many important processes in the brain.
“Many human studies rely on the assumption that disease-relevant epigenetic changes that occur in the brain — which is largely inaccessible and difficult to test — also occur in the blood, which is easily accessible,” says study leader Richard S. Lee, Ph.D., an instructor in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. “This research on mice suggests that the blood can legitimately tell us what is going on in the brain, which is something we were just assuming before, and could lead us to better detection and treatment of mental disorders and for a more empirical way to test whether medications are working.”
For the study, the Johns Hopkins team worked with mice with a rodent version of Cushing’s disease, which is marked by the overproduction and release of cortisol, the primary stress hormone also called glucocorticoid. For four weeks, the mice were given different doses of stress hormones in their drinking water to assess epigenetic changes to FKBP5. The researchers took blood samples weekly to measure the changes and then dissected the brains at the end of the month to study what changes were occurring in the hippocampus as a result of glucocorticoid exposure. The hippocampus, in both mice and humans, is vital to memory formation, information storage and organizational abilities.
The measurements showed that the more stress hormones the mice got, the greater the epigenetic changes in the blood and brain tissue, although the scientists say the brain changes occurred in a different part of the gene than expected. This was what made finding the blood-brain connection very challenging, Lee says.
Also, the more stress hormone, the more RNA from the FKBP5 gene was expressed in the blood and brain, and the greater the association with depression. However, it was the underlying epigenetic changes that proved to be more robust. This is important, because while RNA levels may return to normal after stress hormone levels decrease or change due to small fluctuations in hormone levels, epigenetic changes persist, reflect overall stress hormone exposure and predict how much RNA will be made when stress hormone levels increase.
The team of researchers used an epigenetic assay previously developed in their laboratory that requires just one drop of blood to accurately assess overall exposure to stress hormone over 30 days. Elevated levels of stress hormone exposure are considered a risk factor for mental illness in humans and other mammals.
(Source: hopkinsmedicine.org)
Irreversible tissue loss seen within 40 days of spinal cord injury
The rate and extent of damage to the spinal cord and brain following spinal cord injury have long been a mystery. Now, a joint research effort between the University of Zurich, University Hospital Balgrist and colleagues from University College London have found evidence that patients already have irreversible tissue loss in the spinal cord within 40 days of injury. Using a new imaging measurement technique the impact of therapeutic treatments and rehabilitative interventions can be now determined more quickly and directly than before.
A spinal cord injury changes the functional state and structure of the spinal cord and the brain. For example, the patients’ ability to walk or move their hands can become restricted. How quickly such degenerative changes develop, however, has remained a mystery until now. The assumption was that it took years for patients with a spinal cord injury to also display anatomical changes in the spinal cord and brain above the injury site. For the first time, researchers from the University of Zurich and the Uniklinik Balgrist, along with English colleagues from University College London (UCL), now demonstrate that these changes already occur within 40 days of acute spinal cord injury.
Spinal cord depletes rapidly
The scientists studied 13 patients with acute spinal cord injuries every three months for a year using novel MRI (magnetic resonance imaging) protocols. They discovered that the diameter of the spinal cord had rapidly decreased and was already seven percent smaller after twelve months. A lesser volume decline was also evident in the corticospinal tract, a tract indispensable for motor control, and nerve cells in the sensorimotor cortex. The extent of the degenerative changes coincided with the clinical outcome. “Patients with a greater tissue loss above the injury site recovered less effectively than those with less changes,” explains Patrick Freund, the investigator responsible for the study at the Paraplegic Center Balgrist.
Gaining insights into effect of therapies
Treatments targeting the injured spinal cord have entered clinical trials. Gaining insights into mechanisms of repair and recovery within the first year are crucial. Thanks to the use of the new neuroimaging protocols, Freund says, we now have the possibility of displaying the effect of therapeutic treatments on the central nervous system and of rehabilitative measures more quickly. Consequently, the effect of new therapies can also be recorded more rapidly.
“This study is an excellent example of the value of combining the complementary expertise of the two universities,” says UCL’s Dean of Brain Sciences, Professor Alan Thompson, who is one of the senior authors of the study. “It provides exciting new insights into the complications of spinal cord trauma and gives us the possibility of identifying both imaging biomarkers and therapeutic targets.”
The findings are the result of a new three-year neuroscience partnership between the Neuroscience Centre Zurich (ZNZ) and UCL.
Literature:
Patrick Freund, Nikolaus Weiskopf, John Ashburner, Katharina Wolf, Reto Sutter, Daniel R Altmann, Karl Friston, Alan Thompson, Armin Curt. MRI investigation of the sensorimotor cortex and corticospinal tract after acute spinal cord injury: a prospective longitudinal study. The Lancet Neurology. July 2, 2013.
Newt sequencing may set back efforts to regrow human limbs
The ability of some animals to regenerate tissue is generally considered to be an ancient quality of all multicellular animals. A genetic analysis of newts, however, now suggests that it evolved much more recently.
Tiny and delicate it may be, but the red spotted newt (Notophthalmus viridescens) has tissue-engineering skills that far surpass the most advanced biotechnology labs. The newt can regenerate lost tissue, including heart muscle, components of its central nervous system and even the lens of its eye.
Doctors hope that this skill relies on a basic genetic program that is common — albeit often in latent form — to all animals, including mammals, so that they can harness it in regenerative medicine. Mice, for instance, are able to generate new heart cells after myocardial injury.
The newt study, by Thomas Braun at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany, and his colleagues, suggest that it might not be so simple.
Attempts to analyse the genetics of newts in the same way as for humans, mice and flies have so far been hampered by the enormous size of the newt genome, which is ten times larger than our own. Braun and his colleagues therefore looked at the RNA produced when genes are expressed — known as the transcriptome — and used three analytical techniques to compile their data.
The team compiled the first catalogue of all the RNA transcripts expressed in N. viridescens, looking at both primary and regenerated tissue in the heart, limbs and eyes of both embryos and larvae.
The researchers found more than 120,000 RNA transcripts, of which they estimate 15,000 code for proteins. Of those, 826 were unique to the newt. What is more, several of those sequences were expressed at different levels in regenerated tissue than in primary tissue. Their results are published in Genome Biology.
Worm Regeneration May Lend A Hand in Human Healing
About the size of toenail clippings, planarians are freshwater flatworms that can re-form from tiny slivers. This feature not only lets them repair themselves, but it lets them reproduce by breaking apart and then creating new worms.
Here are two other important features: More than half of planarian genes have parallels in people, and some of their basic physiological systems operate like ours. By studying how these features behave as the worms regenerate, scientists might move one step closer to learning how to generate or regenerate human tissue and cells, such as insulin-producing cells for people with diabetes or nerve cells for patients with spinal cord injuries.
UK scientists have made a breakthrough in a new method of brain tumor diagnosis, offering hope to tens of thousands of people.
Researchers, led by Professor Francis Martin of Lancaster Environment Centre at Lancaster University, have shown that infrared and Raman spectroscopy – coupled with statistical analysis – can be used to tell the difference between normal brain tissue and the different tumor types that may arise in this tissue, based on its individual biochemical-cell ‘fingerprint’.
Spectroscopy is a technique that allows us to analyse light interactions with samples such as tissue by generating a spectrum, which is a reflection of the interrogated sample.
Currently, when surgeons are operating to remove a brain tumor it can be difficult to spot where the tumor ends and normal tissue begins.
But new research published online in Analytical Methods this month has shown it is possible to spot the difference between diseased and normal tissue using Raman spectroscopy – a type of spectroscopy which works effectively on living tissue, giving accurate results in seconds.
Nanoengineers at the University of California, San Diego have developed a novel technology that can fabricate, in mere seconds, microscale three dimensional (3D) structures out of soft, biocompatible hydrogels. Near term, the technology could lead to better systems for growing and studying cells, including stem cells, in the laboratory. Long-term, the goal is to be able to print biological tissues for regenerative medicine. For example, in the future, doctors may repair the damage caused by heart attack by replacing it with tissue that rolled off of a printer.
The biofabrication technique uses a computer projection system and precisely controlled micromirrors to shine light on a selected area of a solution containing photo-sensitive biopolymers and cells. This photo-induced solidification process forms one layer of solid structure at a time, but in a continuous fashion.
Scientists are growing ears, bone and skin in the lab, and doctors are planning more face transplants and other extreme plastic surgeries. Around the country, the most advanced medical tools that exist are now being deployed to help America’s newest veterans and wounded troops.
Top Image: A research engineer at the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital, displays a titanium frame designed for the reconstruction of a human ear, left, and a three dimensional plastic ear model, right, at the lab, in Boston.
Bottom Image: A chart provided by the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital, depicts the progression, from left to right, of implanted tissue engineered for ear development and construction, at the lab in Boston.
(Source: spokesman.com)
Lubricated nanoparticles penetrate the brain
Nanoparticles often meet a sticky end in the brain. In theory, the tiny structures could deliver therapeutic drugs to a brain tumour, but navigating the narrow, syrupy spaces between brain cells is difficult. A spot of lubrication could help.
Nanoparticles (green) coated with poly(ethylene-glycol) (PEG) (Image: Elizabeth Nance, Graeme Woodworth, Kurt Sailor)
Justin Hanes at Johns Hopkins University in Baltimore, Maryland, was surprised to discover just how impermeable brain tissue is to nanoparticles. “It’s very sticky stuff,” he says, similar in adhesiveness to mucus, which protects parts of the body – such as the respiratory system – by trapping foreign particles.
It was thought that the adhesiveness of brain tissue limited the size of particles that can smoothly spread through the brain. Signalling molecules, nutrients and waste products below 64 nanometres in diameter can pass through the tissue with relative ease, but larger nanoparticles – suitable for delivering a payload of drugs to a specific location in the brain – quickly get stuck.
Now Hanes and his colleagues have doubled that size limit. They coated their nanoparticles with a densely-packed polymer shield, which lubricates their surface by preventing electrostatic and hydrophobic interactions with the surrounding tissue. “A nice hydrated shell around the particle prevents it from adhering to cells,” says Hanes.
Tracking the particles
Using this approach, they were able to observe the diffusion of nanoparticles 114 nanometres in diameter through live mouse brains and dissected human and rat brain tissue. Hanes believes the true upper size limit now lies somewhere between 114 nm and 200 nm. “Things were starting to slow down at 114,” he says.
But further research is needed before the team can progress to clinical trials in humans. “At this scale, it is very important to understand where our nanoparticles go once injected into the body,” says team member Elizabeth Nance, also of Johns Hopkins University. “We will need to show that, when combined with a therapeutic agent, these particles are getting to our site of interest, are having the intended effect and are not causing any side effects or toxicity to healthy normal tissue.”
"The effect of this work should be long-term," says Paul Wilson at the University of Warwick in Coventry, UK. The result represents significant progress in the battle to administer drugs within the brain, he says. "More effective and longer-lasting treatments against brain diseases, such as tumours and strokes, will no doubt soon follow."
Source: NewScientist
Harvard scientists have created a type of cyborg tissue by embedding a three-dimensional network of functional, biocompatible, nanoscale wires into engineered human tissues.
The research addresses a concern that has long been associated with work on bioengineered tissue: how to create systems capable of sensing chemical or electrical changes in the tissue after it has been grown and implanted. The system might also represent a solution to researchers’ struggles in developing methods to directly stimulate engineered tissues and measure cellular reactions.
The process of building the networks is similar to that used to etch microchips. Beginning with a two-dimensional substrate, researchers laid out a mesh of organic polymer around nanoscale wires, which serve as the critical sensing elements. Nanoscale electrodes, which connect the nanowire elements, were then built within the mesh to enable nanowire transistors to measure the activity in cells without damaging them. Once completed, the substrate is then dissolved, leaving researchers with a netlike sponge, or a mesh, that can be folded or rolled into a host of three-dimensional shapes. Finally, the networks are porous enough to allow seeding them with cells and encourage those cells to grow in 3-D cultures.
Using heart and nerve cells, the Harvard research team successfully engineered tissues containing embedded nanoscale networks without affecting the cells’ viability or activity. Using the embedded devices, the researchers were then able to detect electrical signals generated by cells deep within the tissue, and to measure changes in those signals in response to cardio- or neuro-stimulating drugs.
Squid Skin Dances When You Blast Cypress Hill At It
The music causes a current to flow in wires hooked up to a squid, exciting its tissue. The video here shows an 8x microscope zoomed on the the dorsal side of the caudal fin of the Longfin Inshore Squid, which produces three colors in its process: brown, red, and yellow.