Rewritable digital data storage in live cells via engineered control of recombination directionality
+ Author Affiliations
Department of Bioengineering, Room 269B, Y2E2 Building, 473 Via Ortega, Stanford University, Stanford, CA 94305
Edited by David Baker, University of Washington, Seattle, WA, and approved April 6, 2012 (received for review February 8, 2012)
The use of synthetic biological systems in research, healthcare, and manufacturing often requires autonomous history-dependent behavior and therefore some form of engineered biological memory. For example, the study or reprogramming of aging, cancer, or development would benefit from genetically encoded counters capable of recording up to several hundred cell division or differentiation events. Although genetic material itself provides a natural data storage medium, tools that allow researchers to reliably and reversibly write information to DNA in vivo are lacking. Here, we demonstrate a re-writeable recombinase addressable data (RAD) module that reliably stores digital information within a chromosome.It is like having a small disc drive associated with your computer now we have that ability with living cells. For more information
New parasitic worm discovery could help 1 billion people worldwide.
Scientists have discovered why some people may be protected from harmful parasitic worms naturally while others cannot in what could lead to new therapies for up to one billion people worldwide.
The University of Manchester researchers have, for the first time, identified
Dr Sumaira Hasnain, the lead researcher said “For the first time, we have discovered that a single component of the mucus barrier, the Muc5ac mucin, is essential for worm expulsion.
Learning who is and isn’t susceptible to parasitic worms can lead to new treatments for people with chronic worm infections.
How does Muc5ac mucin effect cells?
- The abnormal expression of gastric M1/MUC5AC mucin in precancerous lesions and colon cancer.
- Cigarette smoke when it enters lung tissue induces MUC5AC mucin overproduction via tumor necrosis factor-α-converting enzyme in human airway epithelial (NCI-H292) cells.
- During inflammation Nitric oxide (NO) is generally increased in airway diseases. This causes NO to increase the secretion of mucin from the goblet cell and submucosal glands.
“These parasitic worms live in the gut, which is protected by a thick layer of mucus,” explained Dr David Thornton, from the University’s Wellcome Trust Center for Cell Matrix Research. “The mucus barrier is not just slime, but a complex mixture of salts, water and large ‘sugar-coated’ proteins called mucins that give mucus its gel-like properties.
By creating more mucous study mice were able to expel this whipworm from the gut. Importantly, the mucus from these mice contained the mucin, Muc5ac. This mucin is rarely present in the gut, but when it is, it alters the physical properties of the mucus gel.
Mice unable to genetically produce Muc5ac were unable to expel the worms, despite having a strong immune response against these parasites. This resulted in long-term infections.
Muc5ac is also essential for the efficient expulsion from the gut like hookworm, and the spiral threadworm. Together, these worms cause mortality and morbidity in up to one billion people across the globe.
Excerpts and Image 2. courtesy of http://bit.ly/kj9cXm
Image 1. courtesy of http://bit.ly/kuLDE5
Gunning for success
Burn care and healing has been fraught with extreem pain and long crueling amounts of time to heal. Now the prayers have been answered with a gun. Until now burns have usually been treated with skin grafts, which involve taking skin sections from uninjured parts of the patient’s body, or growing sheets of skin artificially, and grafting them over the burn. The grafts can take several weeks or even months to heal, and during the recovery period patients are prone to infections because of the damage to the skin, which is the body’s first line of defense against pathogens.
Scientists have been able to regenerate skin in the laboratory for decades, but the process takes two to three weeks and the sheets of skin produced are fragile. When grafted on, blisters can form beneath it due to secretions, and can push up against the sheet and damage it. Scaring scars lives.
Enter the Skin-cell Gun
The skin sprayer works like a very high tech paint spray gun. Originally developed by Professor Joerg C. Gerlach and colleages of the Department of Surgery at the University of Pittsburg’s McGowan Institute for Regenerative Medicine.
Skin spraying have been in use in Australia, where Dr Fiona Wood of the West Australia Burns Unit developed a method called “spray-on-skin.” Dr Wood’s method uses an aerosol system to spray on cultured skin cells.
This system also cuts healing time to days rather than weeks or months, and the technique substantially cut the death toll in the Bali bombings in 2002.
Dr Gerlach said the new method uses an electronically controlled pneumatic device that does not injure the cells, while the other skin spraying devices are hand-pumped atomizers.
In a process taking only an hour and a half in total, a biopsy is taken from the patient’s undamaged skin and then healthy stem cells are isolated from the biopsy and an aqueous solution containing the cells is sprayed on the burn.
The sprayed wound is then covered with a newly-developed dressing with tubes enmeshed within it and extending from each end. One set of tubes functions as an artery, while the second set functions as a vein. The tubes are connected to an “artificial vascular system” and provide electrolytes, antibiotics, amino acids and glucose to the wound. The dressing keeps the wound clean and sterile, and provides nutrition for the skin stem cells to encourage them to regenerate new skin.
After treatment the wound heals in just days, when it would have taken weeks to heal using traditional treatments. Dr Gerlach said patients had been treated at the Berlin Burn Center and they had regrown skin over a burned ear or an entire face in only a few days.
At the moment the technique can only be used on second-degree burns, but Dr Gerlach hopes it will later be able to tackle third-degree burns as well.
The research is funded by the US Department of Defense under the Armed Forces Institute of Regenerative Medicine (AFIRM) consortium of research institutions, which was formed in 2008 to research better treatments for wounded service personnel.
The Skin-cell Gun was shown on the National Geographic channel in the episode Explorer: How to Build a Beating Heart, which looks at the latest tissue regeneration techniques.
Excerpts and Image courtesy of http://bit.ly/excILy
Brain and spinal cord injuries may soon have a new treatment process that is natural and based on the individual’s own stem cells. Oligodendrocyte, precursor cells (OPCs), are a type of cell found in the brain and nervous system that forms the coating around the nerve cells. These cells are formed during embryo formation in the ventricular zone of the neural tube (embryonic spinal cord), and the cells migrate outwards along the circumference of the tube, and then along its length. During this migration, OPCs actively seek axons around which they can wrap
their processes once they have differentiated into oligodendrocytes. Myelination, the process by which oligodendrocytes wrap their processes around nerve fibers, begins towards the end of embryonic development, and continues post-natally coating around the nerve cells.
These cells are formed during embryo formation in the ventricular zone of the neural tube (embryonic spinal cord), and the cells migrate outwards along the circumference of the tube, and then along its length. During this migration, OPCs actively seek axons around which they can wrap their processes once they have differentiated into oligodendrocytes. Myelination, the process by which oligodendrocytes wrap their processes around nerve fibers, begins towards the end of embryonic development, and continues postnatally.
Throughout their migration, these cells extend and retract filopodia-like processes to obtain cues from their surroundings. Upon coming into contact with neighboring OPCs. These hair or cilia like projections are withdrawn and then extended in the opposite direction. This seems to be a mutual repulsion mechanism which ensures that OPCs are evenly distributed along the length of the axons they will myelinate (coat). An axon is a long, slender extension of a nerve cell, or neuron, that conducts electrical impulses away from the neuron’s cell body
Oligodendrocyte precursor cells (OPCs) comprise 5% of the cells in the adult brain, where they are the most proliferative cell present. They can generate both neurons and glial cells, making them an important stem cell population in the adult brain.
The bottom line is that this animal model with the injection of hESC-OPCs cells has demonstrated that remyelination of the cervical injury site and the restoration of movement to the limbs of these animals may help restore function in spinal cord injuries victims in the future.
This frenzy over upping the number of vaccines to supposedly prevent a host of nasty diseases –at what price?
“North American children are now the most vaccinated on earth. Since 1980, Canadian vaccine schedules have more than doubled the types of vaccines given; for the first 4-6 yrs of life alone, Public Health now recommends 43 doses of thirteen different vaccines. The first 8 doses are given in four shots at two months of age. It’s been declared that today’s children are the first generation whose parents will outlive them. Why?
Today, 10% of Canadian children have life threatening afflictions. In the last 25 years, concurrent with vaccine increase, there’ve been huge declines in children’s health in many categories:
* Autism – increased over 1000 times in less than one generation;
* Juvenile Diabetes – 104% increase since 1980; * Anaphylactic Food Allergies – doubled in the last decade;
* All types of Allergies – increased nearly six times;
* Obesity – now almost 20%, 3 times the prevalence in 1980;
*Attention Deficit Disorder – now almost 10%. (1)
Dr. Sherri Tenpenny, DO in the May 1, 2006 issue of NewsWithViews.com stated, “Multiple studies published in highly reputable publications have documented that flu shots are ineffective in all ages.” Besides being ineffective the adjuvant the biochemical catalyst added to the vaccine can pose further health risks.
After the Gulf War vets returned with a cascade of immuno -reactions called Gulf War syndrome.included “arthritis, fibromyalgia, lymphadenopathy, rashes, photosensitive rashes, malar rashes, chronic fatigue, chronic headaches, abnormal body hair loss, non-healing skin lesions, aphthous ulcers, dizziness, weakness, memory loss, seizures, mood changes, neuropsychiatric problems, anti-thyroid effects, anemia, elevated ESR (erythrocyte sedimentation rate), systemic lupus erythematosus, multiple sclerosis, ALS, Raynaud’s phenomenon, Sjorgren’s syndrome, chronic diarrhea, night sweats and low-grade fever.” research has attributed these symptoms to three batches of immunizations using squalen based adjuvant.(1)
Squalene is an oil-based adjuvant compound called MF-59. The main function of the adjuvant is to supercharge the live or dead virus(s) main ingredient in the diluted vaccine to make them more potent and kick start the response to the flu in the body. Two H1N1 vaccines being developed by companies Novartis and GlaxoSmithKline are adding squalene adjuvants to boost immunogenicity and dramatically reduce the amount of viral antigen needed. This translates to much faster production of desired vaccine quantities. Novartis’s proprietary squalene adjuvant for their H1N1 vaccine is MF59. Glaxo’s is ASO3. MF59 has yet to be approved by the FDA for use in any U.S. vaccine.
Natural Squalene as an oil molecule is native to your body. It is found throughout your nervous system and brain. In fact, olive oil will bless you with natural squalene and by consuming it will build your immune system as long as you are not sensitive or allergic to it.
Why does the body go to war with injected squalene compounds?
Injection is an abnormal route of entry which incites your immune system to attack all the squalene in your body, not just the vaccine adjuvant. Squalene compounded vaccines has been fingered at a possible culprit in the post Gulf War multiple health issues that these veterans continue to suffer. Two H1N1 vaccines being developed by companies Novartis and GlaxoSmithKline are adding squalene adjuvants to boost immunogenicity and dramatically reduce the amount of viral antigen needed. This translates to much faster production of desired vaccine quantities. Novartis’s proprietary squalene adjuvant for their H1N1 vaccine is MF59. Glaxo’s is ASO3. MF59 has yet to be approved by the FDA for use in any U.S. vaccine.
Flu vaccines can also contain a number of chemical toxins, including ethylene glycol (antifreeze), formaldehyde, phenol (carbolic acid) and even antibiotics like Neomycin and streptomycin. In addition to the viruses and aluminum and squalene. Vaccinations are biochemical cocktails for supression of the native immune systems that will not is help build immunity to potentially harmful organisms that cause illness and disease.
However, your body’s immune system is already designed to do this in response to organisms that invade your body naturally. Build your immunity by eating organic healthy raw and steamed fruits and seasonal veggies, staying well hydrated, getting plenty of sleep and exercise in fresh air.
Excerpts courtesy of http://vran.org/about-vaccines/vaccine-essentials/vaccination-the-basics/
Excerpts courtesy of http://en.wikipedia.org/wiki/Immunologic_adjuvant
Excerpts courtesy of http://en.wikipedia.org/wiki/Squalene
Excerpts courtesy of http://newresearchfindingstwo.blogspot.com/2009/07/squalene.html
Image 1. the flu virus courtesy of Biochemistryquestions.wordpress.com/some-basic-biochemistry-h1n1-virus/
Image 2. squalene courtesy of En.wikipedia.org/wiki/Squalene
HIV and Women
Women usually develop lower viral levels than men following acute HIV-1 infection.
Women with similar viral loads. will develop AIDS faster. Why?
Research team based at the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard has found that a receptor molecule involved in the first-line recognition of HIV-1 responds to the virus differently in women, leading to subsequent differences in chronic T cell activation, a known predictor of disease progression. Their paper, which will be published in an upcoming issue of Nature Medicine.
Excerpts courtesy of LabSpace.net labspaces.net/98592/StudymayexplainwhyHIVprogressesfasterinwomenthaninmen
Image courtesy of Wikimedia.com wikimedia.org/wikipedia/commons/1/1a/HIV-budding-Color.jpg
Comprehensive Study of Brain Tumors
New Genetic Mutations, Core Pathway
“The Cancer Genome Atlas (TCGA) Research Network, a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), reported the first results of its large-scale, comprehensive study of the most common form of brain cancer, glioblastoma (GBM). “Sept. 4, 2008, in the advance online edition of the journal Nature, the TCGA team describes the discovery of new genetic mutations and other types of DNA alterations with potential implications for the diagnosis and treatment of GBM.
Among the TCGA findings are the identification of many gene mutations involved in GBM, including three previously unrecognized mutations that occur with significant frequency; and the delineation of core pathways disrupted in this type of brain cancer. Among the most exciting results is an unexpected observation that points to a potential mechanism of resistance to a common chemotherapy drug used for brain cancer.
“… The more we learn about the molecular basis of glioblastoma, the more swiftly we can develop better ways of helping patients,” said NIH Director Elias A. Zerhouni, M.D.
Like most cancers, GBM arises from changes that accumulate in cells’ DNA over the course of a person’s life – changes that may eventually lead to the cells’ uncontrolled growth. However, until recently, scientists have understood little about the precise nature of these DNA changes and their impact on key biological pathways that are important to the development of new interventions.
TCGA researchers sequenced 601 genes in GBM samples and matched control tissue, uncovering three significant genetic mutations not previously reported to be common in GBM. The affected genes were: NF1, a gene previously identified as the cause of neurofibromatosis 1, a rare, inherited disorder characterized by uncontrolled tissue growth along nerves; ERBB2, a gene that is well-known for its involvement in breast cancer; and PIK3R1, a gene that influences activity of an enzyme called PI3 kinase that is deregulated in many cancers. PI3 kinase already is a major target for therapeutic development. The discovery of frequent mutations in the PIK3R1 gene means that GBM patients’ responses to PI3 kinase inhibitors may be dictated by whether or not their tumors have mutated versions of the gene.
The TCGA team combined sequencing data with other types of genome characterization information… to generate an unprecedented overview that delineated core biological pathways potentially involved in GBM. The three pathways, each of which was found to be disrupted in more than three-quarters of GBM tumors, were: the CDK/cyclin/CDK inhibitor/RB pathway, which is involved in the regulation of cell division; the p53 pathway, which is involved in response to DNA damage and cell death; and the RTK/RAS/PI3K pathway, which is involved in the regulation of growth factor signals.
The three pathways were interconnected and coordinately deregulated in most of the GBM tumors analyzed. Therefore, combination therapies directed against all three pathways may offer an effective strategy, the TCGA researchers state.
As in the Human Genome Project, TCGA data are being made rapidly available to the research community through a database, http://cancergenome.nih.gov/dataportal. The database provides access to public datasets, and with required review and approval, allows researchers access to more in-depth data.
Additional information about NHGRI can be found at its Web site,” http://www.genome.gov.