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    human-retina-genes-antibodies-gentaurInvestigators at Massachusetts Eye and Ear and Harvard Medical School have published the most thorough description of gene expression in the human retina reported to date. In a study published today in the journal BMC Genomics, Drs. Michael Farkas, Eric Pierce and colleagues in the Ocular Genomics Institute (OGI) at Mass. Eye and Ear reported a complete catalog of the genes expressed in the retina.

    The retina is the neural tissue in the back of the eye that initiates vision.  It is responsible to receiving light signals, converting them into neurologic signals and sending those signals to the brain so that we can see.  If one thinks of the eye as a camera, the retina in the “film” in the camera. For these studies, the investigators used a technique called RNA sequencing (RNA-seq) to identify all of the messenger RNAs (mRNAs) produced in the human retina.  The resulting catalog of expressed genes, or transcriptome, demonstrates that the majority of the 20,000+ genes in the human body are expressed in the retina.  This in itself is not surprising, because the retina is a complex tissue comprised of 60 cell types.

    In a more surprising result, Dr. Farkas and colleagues identified almost 30,000 novel exons and over 100 potential novel genes that had not been identified previously. Exons are the portions of the genome that are used to encode proteins or other genetic elements.  The investigators validated almost 15,000 of these novel transcript features and found that more than 99 percent of them could be reproducibly detected. Several thousand of the novel exons appear to be used specifically in the retina.  In total, the newly detected mRNA sequence increased the number of exons identified in the human genome by 3 percent. 

    “While this may not sound like a lot, it shows that there is more to discover about the human genome, and that each tissue may use distinct parts of the genome,” said Dr. Pierce, Director of the OGI and the Solman and Libe Friedman Associate Professor of Ophthalmology, Harvard Medical School.

    This work is valuable to help scientists understand how the retina worksand how it is affected by disease. For example, Dr. Pierce and colleagues in the OGI study inherited retinal degenerations, which are common causes of vision loss. These diseases are caused by misspellings or mutations in genes that are needed for vision. To date, investigators have identified more than 200 retinal degeneration disease genes, but still can’t find the cause of disease for up to half of the patients affected by these disorders. Identification of new exons used in the retina may help find the cause of disease in these patients. 

    Identifying the genetic cause of patients’ retinal degeneration has become especially important with the recent success of clinical trials of gene therapy for RPE65 Leber congenital amaurosis (LCA). As a follow-up to these initial proof-of-concept trials, clinical trials of gene therapy for four other genetic forms of inherited retinal degeneration are currently in progress. Further, studies in animal models have reported successful gene therapy for multiple additional genetic types of IRD. There is thus an unprecedented opportunity to translate research progress into provide sight preserving and/or restoring treatment to patients with retinal degenerative disorders.

    About Massachusetts Eye and Ear 
    Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck.  After uniting with Schepens Eye Research Institute in 2011, Mass. Eye and Ear in Boston became the world's largest vision and hearing research center, offering hope and healing to patients everywhere through discovery and innovation.  Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships.  Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex.  U.S. News & World Report’s “Best Hospitals Survey” has consistently ranked the Mass. Eye and Ear Departments of Otolaryngology and Ophthalmology as among the top hospitals in the nation. Mass. Eye and Ear is home to the Ocular Genomics Institute which aims to translate the promise of personalized genomic medicine into clinical care for ophthalmic disorders. 

    UCLA researchers, in a finding that runs counter to conventional wisdom, have discovered for the first time that a gene thought to express a protein in all cells that come under stress is instead expressed only in specific cell types.

    The group, from the Jules Stein Eye Institute and UCLA Pulmonary and Critical Care Medicine, focused on αB-Crystallin, a small heat shock protein. Heat shock proteins are a class of functionally-related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to taxing environmental conditions, such as infection, inflammation, exercise, exposure to toxins and other stressors.

    αB-Crystallin may be associated with certain cancers and could be developed into a biomarker to monitor for diseases such as multiple sclerosis, age-related macular degeneration, heart muscle degeneration and clouding of the eye lens. Any discoveries about how this protein is regulated and its molecular biology may reveal potential targets for novel therapies, said study first author Zhe Jing, a research associate in UCLA Pulmonary and Critical Care Medicine.

    "If you use a certain cell type, this protein can be induced when the cells are stressed, but that doesn't happen in a different cell type," said Jing. "This novel finding does conflict with what has been thought, that this protein could be induced in any cell type."

    The findings of this two-year study are published in the most recent issue of the journal Cell Stress and Chaperones, a peer-reviewed journal in the fields of cell stress response.

    The UCLA team did the study using four cell lines -- two epithelial cells lines and two fibroblast cells lines. They found that the protein cannot be induced by stress in epithelial cells, in which 80 percent of cancers arise. It can, however, be induced in the fibroblasts that make up muscle tissue.

    The significant finding in this investigation is that, in certain cell types, only one specific heat shock factor controls the expression of αB-Crystallin. For example, in the epithelial cell lines, it is heat shock factor 4 (HSF4), while a different heat shock factor, (HSF1), plays this role in the fibroblast cells lines.

    In the past, the data has indicated that a heat shock factor could control the expression of αB-Crystallin randomly and equally. However, Jing's discovery overrides this rule. His findings strongly suggest the "preference" of the αB-Crystallin to heat shock factors in certain cells may be correlated with its versatility to various diseases.

    "Considering the multiple roles of αB-Crystallin in so many diseases, the access of the HSF1 and HSF4 to the αB-Crystallin gene dictated by the certain cell type may be what is helping to cause certain diseases," Jing said. "If we can uncover the cascade of events that result in disease, we may be able to come up with strategies to block or interrupt that cascade."

    Going forward, Jing and the research team will validate what they found in this study by examining single cells, which provides a greater challenge but may lead to further discoveries.

    The study was funded by the National Institutes of Health.

    Scientists at Indiana University and international collaborators have found a way to link two hormones into a single molecule, producing a more effective therapy with fewer side effects for potential use as treatment for obesity and related medical conditions.

    The studies were carried out in the laboratories of Richard DiMarchi, the Standiford H. Cox Distinguished Professor of Chemistry and the Linda & Jack Gill Chair in Biomolecular Sciences in the IU Bloomington College of Arts and Sciences, and of Matthias Tschöp, professor of medicine and director of the Institute of Diabetes and Obesity, Helmholtz Center Munich, Germany.

    Results were published online this week by the journal Nature Medicine.

    Researchers combined a peptide hormone from the digestive system, GLP-1, with the hormone estrogen and administered it to obese laboratory mice. While both GLP-1 and estrogen have demonstrated efficacy as therapy for obesity and adult-onset diabetes, the combination was more effective in producing weight loss and other beneficial results than using either compound on its own. And it produced fewer adverse effects, such as excessive tissue growth linked to tumor formation.

    "We find that combining the hormones as a single molecule dramatically enhanced their efficacy and their safety," DiMarchi said. "The combination improves the ability to lower body weight and the ability to manage glucose, and it does so without showing the hallmark toxicities associated with estrogen."

    The researchers believe GLP-1 acts as a "medicinal chaperone," targeting estrogen to the hypothalamus and pancreas, which are involved with metabolic processes. The precise targeting reduces the likelihood that the estrogen will produce negative effects, such as cancer and stroke.

    Brian Finan, a former doctoral student in DiMarchi's lab, is the lead author of the paper, "Targeted estrogen delivery reverses the metabolic syndrome." Co-authors include Bin Yang and Vasily Gelfanov, research scientists in the IU Bloomington Department of Chemistry, and DiMarchi. Finan is now a post-doctoral researcher at the Helmholtz Zentrum München in Germany, directed by Tschöp, who is DiMarchi's longtime collaborator and a corresponding co-author. Affiliations of the other 20 co-authors include the University of Cincinnati where, also led by Tschöp, many of the in vivo pharmacology and molecular mechanism studies were conducted; Northwestern University; and research laboratories in Germany and China.

    Associated with what health authorities are calling a global epidemic of obesity, the metabolic syndrome consists of obesity associated with other factors such as high blood pressure, high triglycerides, hyperglycemia and low HDL cholesterol. The International Diabetes Federation estimates that as much as 20 percent of the world's adult population has some form of the metabolic syndrome and that they are three times as likely to have a heart attack or stroke and five times as likely to develop adult-onset diabetes as people without the syndrome.

    DiMarchi said investigation continues in the optimization of the peptide-based hormone conjugates with an emphasis on determining the specific mechanism of biological action and identification of an optimal drug candidate suitable for human study. The combination of other peptides and nuclear hormones for targeting other medical conditions holds considerable promise and opportunity for future research.

    Partial funding of the research was provided by Marcadia Biotech and more recently Roche Pharma. Marcadia is a company that DiMarchi co-founded and was acquired in 2010 by Roche Pharma, to which he remains a research consultant.

     

    Proteins found in soybeans could inhibit the growth of colon, liver and lung cancers.  Soybean meal is a bi-product following oil extraction from soybean seeds. It is rich in protein, which usually makes up around 40% of the nutritional components of the seeds and dependent on the line, and can also contain high oleic acid (a monounsaturated omega-9 fatty acid).

    The study looked at the role soybeans could have in the prevention of cancer. Using a variety of soybean lines which were high in oleic acid and protein, the researchers looked to monitor bioactivity between the peptides derived from the meals of soybean and various types of human cancer cells.

    The study showed that peptides derived from soybean meal significantly inhibited cell growth by 73% for colon cancer, 70% for liver cancer and 68% for lung cancer cells using human cell lines. This shows that the selected high oleic acid soybean lines could have a potential nutraceutical affect in helping to reduce the growth of several types of cancer cells.

    Friday, 02 August 2013 17:00

    Blood test to detect Alzheimer's early

    microrna-gene-targeting-rosa26-feeder-cells-human-primary-cells-mef cells-rat-knock-out-stem-cell-characterization-teratoma-formation-embryoid-body

    Disease develops years before the first symptoms appear

    Scientists have developed a simple blood test that can help identify Alzheimer's disease.

    Experts are of the opinion that the method will likely lead to a revolutionary breakthrough in the fight against the disease, since the only way used before her diagnosis at necropsy.

    The disease can begin a decade before her first experience symptoms such as confusion and memory loss.

    Scientists from the University of Saarland in Germany focused its attention on microRNA - small molecules contained in body fluids and influence the expression of genes.

    The team determined that the levels are different microRNA in individual patients affected by Alzheimer's disease.

    The results were published in Genome Biology

    mouse-samo-s-glavaResearchers from Massachusetts General Hospital in Boston are getting closer to the moment will be using tissue engineering to create ear shells for patients who are born with malformed or have lost those parts of your body to incidents BBC .

    In tissue engineering material is used by the patient and in the laboratory are "grown" organs to replace those missing in people for various reasons. Years ago, scientists were able to raise their ear about the size of a baby on the back of a mouse.

    In yet another accomplishment that reported the journal Journal of the Royal Society Interface, talking about the following: scientists take living tissue from cows or sheep and then "grow" on a flexible matrix of titanium, reproduced on the basis of three-dimensional representation of a real human cochlea. Then again comes to the aid experimental mouse - rat immunosuppressed organ is implanted to reach the required size.

    Dr. Thomas Cervantes, who heads the team, told the media that the first such human ear in real terms, it's a fact. After 12 weeks, the rat donor is willing to part with their ear and it should be provided to the patient for implantation.

    The polymerase chain reaction (PCR) is a common technique used to amplify, or copy, pieces of DNA. Amplified DNA is then used in genetic analyses for everything from medicine to forensics. In plant research, PCR is a vital step in detecting and sequencing genes, and its applications are endless. However, compounds found in plants often inhibit PCR. Researchers at the University of Southern Mississippi discovered that the use of an additive allows PCR to successfully amplify DNA from once problematic plants.

    PCR is widely used in plant sciences but is not 100 percent reliable. Many plant researchers encounter roadblocks when implementing PCR. For example, many plant species contain phenolic compounds that deter herbivores. These compounds are often extracted along with plant DNA and can stop PCR from working.

    Graduate student Tharangamala Samarakoon and colleagues have found a technique to overcome many of these inhibitory plant compounds. They added a reagent to the PCR mixture that contains three ingredients: trehalose, bovine serum albumin, and polysorbate-20 (all three abbreviated TBT-PAR). "Unlike several other studies, TBT-PAR works at the PCR stage instead of at the DNA extraction stage, so it has promise for pigeon-holed and half-forgotten extractions that previously failed to be amplified using PCR," says Samarakoon. The authors published their research in the January issue of Applications in Plant Sciences.

    Samarakoon tested the TBT-PAR reagent on DNA extracted from tropical and temperate species across four plant families, including Achariaceae, Asteraceae, Lacistemataceae, and Samydaceae. PCR with TBT-PAR successfully amplified DNA for all species, whereas standard DNA extraction and PCR techniques consistently failed.

    TBT-PAR enhanced PCR for DNA extracted from fresh, silica-dried, and herbarium plant material. "Since we study tropical plants, many of which are geographically restricted or rare," explains Samarakoon, "herbarium material is sometimes all that we have available for DNA extraction, and curators are gracious to allow even a small destructive sampling for a single extraction attempt. We want that one attempt, of course, to be successful." Samarakoon predicts that inhibitory plant compounds could be the underlying cause of many PCR failures in herbarium specimens and hopes TBT-PAR will have widespread benefits in herbarium specimen DNA amplification. 

    TBT-PAR was first used in the PCR detection of a shrimp virus by co-author Shiao Wang and his colleagues. "The additive has also been helpful in a colleague's lab where they had trouble amplifying DNA from gopher tortoise ticks, so its utility extends beyond plants," comments Samarakoon. TBT-PAR has the potential for broad use in PCR techniques across DNA samples, species, and taxa.

    The article will be published in the first issue of Applications in Plant Sciences (APPS), a new journal released by the Botanical Society of America. Theresa Culley, Editor-in-Chief of APPS, describes the new journal as a venue to "expedite the dissemination of innovative information encompassing all areas of the plant sciences, including but not limited to genetics, structure, development, evolution, systematics, and ecology."APPS publishes new methods in plant sciences -- an important niche to fill in an age of rapid technological advances.

    -cells-rat-models-gene-targeting-rosa26-feeder-cells-human-primary-cells-mef cells-rat-knock-outMax Planck scientists in Jena, Germany, have discovered an unusual regulation of enzymes that catalyze chain elongation in an important secondary metabolism, the terpenoid pathway. In the horseradish leaf beetle Phaedon cochleariae a single enzyme can trigger the production of two completely different substances depending on whether it is regulated by cobalt, manganese or magnesium ions: iridoids, which are defensive substances the larvae use to repel predators, or juvenile hormones, which control insect's development. Insects unlike plants do not have a large arsenal of the proteins called isoprenyl diphosphate synthases. Therefore they may have developed another efficient option to channel metabolites into the different directions of terpenoid metabolism by using metal ions for control.
    Natural products: 40,000 terpenes
    Apart from the primary metabolism which produces substances that ensure the survival of the cells, there are additional biosynthetic pathways in all organisms. Their products may be less important for a single cell, but they can nevertheless be essential for the whole organism. These pathways are summarized as secondary metabolism. One of them is the terpenoid pathway: with more than 40,000 different known structures it generates one of the largest classes of natural products. Terpenoid molecules have diverse functions and can act as components in molecular signaling pathways, as toxins, fragrances or hormones.
    The basic unit of all terpenes is a simple molecule containing five carbon atoms that can be joined to chains of different length. There are monoterpenes (C10 units, 2 x C5), sesquiterpenes (C15, 3 x C5), and even polymers, such as natural rubber, which comprises several hundred C5 units. Special enzymes mediate chain elongation. These enzymes have attracted the curiosity of scientists at the Max Planck Institute for Chemical Ecology, Jena, and the Leibniz Institute for Plant Biochemistry in Halle. They studied mechanistic alternatives of how chain elongation is regulated.
    Metal ions instead of specialized enzymes
    Enzymes involved in chain elongation belong to the group of isoprenyl diphosphate synthases. Such an enzyme was isolated from larvae of the horseradish leaf beetle Phaedon cochleariae. It raised the interest of Antje Burse, project group leader in the Department of Bioorganic Chemistry at the Max Planck Institute for Chemical Ecology.
    Experiments with larvae in which the enzyme encoding gene was silenced showed that the protein was involved in the formation of the C10 monoterpene chrysomelidial that larvae produce to defend themselves against predators. The larvae accumulate this monoterpene in special glands and release it as a defensive secretion when they are attacked by their enemies, such as ants.
    However, surprising results emerged after comprehensive biochemical characterization of the enzyme. "After we had conducted an in vitro analysis of the protein, including measurements of product formation in the presence of different metal ions as co-factors, we were surprised to discover that only geranyl diphosphate (C10), a precursor for the defensive substance chrysomelidial, was produced after addition of cobalt and manganese ions. On the other hand, adding magnesium ions resulted in the formation of farnesyl diphosphate (C15), a potential precursor for juvenile hormones, which is 5 carbon atoms longer," says the scientist. All three metals were found in larval tissue, leading to the assumption that enzyme catalysis is directed by the different metal co-factors in the larvae, whichever is predominant in amount: Towards toxin or hormone − physiologically a major difference.
    Sequence comparisons cannot replace a thorough biochemical analysis
    How the different metal ions modify the product range of the enzyme is still unclear. It is very likely that the varying atomic radii of the metal ions involved in the catalysis effect changes in the spatial structure of the enzyme, which prevent or allow the admission of a third C5 unit and hence result in the production of C10 or C15 molecules.
    "Our experiments provide two important findings," says Wilhelm Boland, director at the Max Planck Institute. "First, the directing influence of metal ions on the product formation of isoprenyl diphosphate synthases is a novel "control element" in the regulation of the terpene metabolism which should be included in future experimental settings. And secondly: The diversity of terpenoid molecules cannot be attributed solely to the broad substrate specificity of some enzymes in the last steps of the metabolic pathway, but is in fact already inherent in early biosynthetic steps." Nature continues to provide interesting answers to the question how organisms manage to produce tens of thousands of different secondary metabolites.

    hpv in1-pluripotency-marker-cf-1-gene-knock-in-technology-ipsc-generation-cell-line-gene-modification-cel-line-model-diseaseScientists compared the results of blood tests, involving 135 people who were about to become ill from throat cancer and 1599 healthy volunteers. It was found that 35 percent of those affected by cancer of the throat have antibodies while this is true for less than 1 percent of healthy subjects.

    One-third of diagnosed with throat cancer are infected with human papilloma virus, according to a British study, transmits the BBC.

    This virus is the main cause of cervical cancer. There are over 100 types of human papillomavirus. Many people in a moment of their lives infected with human popiloma virus, but the immune system protecting them. Two strains of human papilloma virus are associated with the highest risk of cancer - HPV-16 and HPV-18. It is thought that HPV-16 is responsible for about 60 percent of cervical cancers, 80 per cent of the cancer of the anus and 60 percent of cancers of the mouth.
    The study focuses on the relationship between human papillomavirus and cancer in the back of the throat - oropharyngeal cancer.

    Researchers from Oxford University studied the results of blood tests within a large-scale study on lifestyle and cancer. At the beginning of the study all participants were healthy and that the blood samples. Scientists were able to examine for the presence of antibodies that are as markers for E6, one of the key proteins of the human papilloma virus. E6 destroyed part of the protective system of the cells, that can prevent the development of cancer. Possessing antibodies means that the human papilloma virus has overcome this protection and caused cancerous changes in cells.

    Scientists compared the results of blood tests, involving 135 people who were about to become ill from throat cancer and 1599 healthy volunteers. It was found that 35 percent of those affected by cancer of the throat have antibodies while this is true for less than 1 percent of healthy subjects. However, these patients have a greater chance to fight the disease than those whose disease is related to other causes, such as smoking and alcohol consumption. The results were published in the Journal of Clinical Oncology.

    Important new research from UMass Medical School demonstrates how exosomes shuttle proteins from neurons to muscle cells where they take part in critical signaling mechanisms, an exciting discovery that means these tiny vehicles could one day be loaded with therapeutic agents, such as RNA interference (RNAi), and directly target disease-carrying cells.

    The study, published this month in the journal Neuron, is the first evidence that exosomes can transfer membrane proteins that play an important role in cell-to-cell signaling in the nervous system.

    "There has been a long-held belief that certain cellular materials, such as integral membrane proteins, are unable to pass from one cell to another, essentially trapping them in the cell where they are made," said Vivian Budnik, PhD, professor of neurobiology and lead author of the study. "What we've shown in this study is that these cellular materials can actually move between different cell types by riding in the membrane of exosomes.

    "What is so exciting about this discovery is that these exosomes can deliver materials from one cell, over a distance, to a very specific and different cell," said Dr. Budnik. "Once inside the recipient cell, the materials contained in the exosome can influence or perform processes in the new cell. This raises the enticing possibility that exosomes can be packed with gene therapies, such as RNAi, and delivered to diseased cells where they could have a therapeutic effect for people."

    Discovered in the mid-80s, exosomes have only recently attracted the attention of scientists at large, according to Budnik. Exosomes are small vesicles containing cellular materials such as microRNA, messenger RNAs (mRNAs) and proteins, packaged inside larger, membrane-bound bodies called multivesicular bodies (MVBs) inside cells. When MVBs containing exosomes fuse with the cell plasma membrane, they release these exosome vesicles into the extracellular space. Once outside the cell, exosomes can then travel to other cells, where they are taken up. The recipient cells can then use the materials contained within exosomes, influencing cellular function and allowing the recipient cell to carry out certain processes that it might not be able to complete otherwise.

    Budnik and colleagues made this startling discovery while investigating how the synapses at the end of neurons and nearby muscle cells communicate in the developing Drosophila fruit fly to form the neuromuscular junction (NMJ). The NMJ is essential for transmitting electrical signals between neurons and muscles, allowing the organism to move and control important physiological processes. Alterations of the NMJ can lead to devastating diseases, such as muscular dystrophy and Amyotrophic lateral sclerosis (ALS). Understanding how the NMJ develops and is maintained is important for human health.

    As organisms develop, the synapse and muscle cell need to grow in concert. If one or the other grows too quickly or not quickly enough, it could have dire consequences for the ability of the organism to move and survive. To coordinate development, signals are sent from the neuron to the muscle cell (anterograde signals) and from the muscle cell to the neuron (retrograde signals). However, the identity of these signals and how their release is coordinated is poorly understood.

    Normally, the vesicle protein Synaptotagmin 4 (Syt4) is found in both the synapse and the muscle cells. Previous knockout experiments eliminating the Syt4 protein from Drosophila have resulted in stunted NMJs. Suspecting that Syt4 played an important role in retrograde signaling at the developing NMJ, Budnik and colleagues used knockdown experiments to decrease Syt4 protein levels in either the neurons or the muscle cells. Surprisingly, when RNAi was used to knockdown Syt4 in the neurons alone, Syt4 protein was eliminated in both neurons and muscles. The opposite was not the case. When Syt4 was knocked down in muscle cells only, there was no change in the levels of Syt4 in either muscles or neurons.

    To confirm this, Budnik and colleagues inserted a Syt4 gene into the neurons of a Drosophila mutant completely lacking the normal protein. This restored Syt4 in both neurons and muscle cells. Further experiments suggested that the only source of Syt4 is the neuron. These observations were consistent with the model that Syt4 is actually transferred from neurons to muscle cells. As a transmembrane protein, however, Syt4 was thought to be unable to move from one cell to another through traditional avenues. How the Syt4 protein was moving from neuron to muscle cell was unclear.

    Knowing that exosomes had been observed to carry transmembrane proteins in other systems and from their own work on the Drosophila NMJ, Budnik and colleagues began testing to see if exosomes could be the vehicle responsible for carrying Syt4 form neurons to muscles. "We had previously observed that it was possible to transfer transmembrane proteins across the NMJ through exosomes, a process also observed in the immune system," said Budnik. "We suspect this was how Syt4 was making its way from the neuron to the muscle."

    When exosomes were purified from cultured cells containing Syt4, they found that exosomes indeed contained Syt4. In addition, when these purified exosomes were applied to cultured muscle cells from fly embryos, these cells were able to take up the purified Syt4 exosomes. Taken together, these findings indicate that Syt4 plays a critical role in the signaling process between synapse and muscle cell that allows for coordinated development of the NMJ. While Syt4 is required to release a retrograde signal from muscle to neuron, a component of this retrograde signal must be supplied from the neuron to the muscle. This establishes a positive feedback loop that ensures coordinated growth of the NMJ. Equally important is the finding that this feedback mechanism is enabled by the use of exosomes, which can shuttle transmembrane proteins across cells.

    "While this discovery greatly enhances our understanding of how the neural muscular junction develops and works, it also has tremendous promise as a potential vector for targeted genetic therapies," said Budnik. "More work needs to be done, but this study significantly supports the possibility that exosomes could be loaded with therapeutic agents and delivered to specific cells in patients."