Posts tagged medicine
Articles and news from the latest research reports.
Scientists Turn Muscular Dystrophy Defect On and Off in Cells
For the first time, scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified small molecules that allow for complete control over a genetic defect responsible for the most common adult onset form of muscular dystrophy. These small molecules will enable scientists to investigate potential new therapies and to study the long-term impact of the disease.
“This is the first example I know of at all where someone can literally turn on and off a disease,” said TSRI Associate Professor Matthew Disney, whose new research was published June 28, 2013, by the journal Nature Communications. “This easy approach is an entirely new way to turn a genetic defect off or on.”
Myotonic dystrophy is an inherited disorder, the most common form of a group of conditions called muscular dystrophies that involve progressive muscle wasting and weakness. Myotonic dystrophy type 1 is caused a type of RNA defect known as a “triplet repeat,” a series of three nucleotides repeated more times than normal in an individual’s genetic code. In this case, a cytosine-uracil-guanine (CUG) triplet repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities.
To find drug candidates that act against the defect, Disney and his colleagues analyzed the results of a National Institutes of Health (NIH)-sponsored screen of more than 300,000 small molecules that inhibit a critical RNA-protein complex in the disease.
The team divided the NIH hits into three “buckets”—the first group bound RNA, the second bound protein, and a third whose mechanism was unclear. The researchers then studied the compounds by looking at their effect on human muscle tissue both with and without the defect.
Startlingly, diseased muscle tissue treated with RNA-binding compounds caused signs of the disease to go away. In contrast, both healthy and diseased tissue treated with the protein-binding compounds showed the opposite effect—signs of the disease either appeared (in healthy tissue) or became worse.
The new compounds will serve as useful tools to study the disease on a molecular level. “In complex diseases, there are always unanticipated mechanisms,” Disney noted. “Now that we can reverse the disease at will, we can study those aspects of it.”
In addition, Disney said, with the new discovery, scientists will be able to develop a greater understanding of how to control RNA splicing with small molecules. RNA splicing can cause a host of diseases that range from sickle-cell disease to cancer, yet prior to this study, no tools were available to control specific RNA splicing.
(Source: scripps.edu)
How brain compensates for hearing loss points to new glue ear therapies
Insights into how the brain compensates for temporary hearing loss during infancy, such as that commonly experienced by children with glue ear, have been revealed in a research study in ferrets. The Wellcome Trust-funded study could point to new therapies for glue ear and has implications for the design of hearing aid devices.
Normally, the brain works out where sounds are coming from by relying on information from both ears located on opposite sides of the head, such as differences in volume and time delay in sounds reaching the two ears. The shape of the outer ear also helps us to interpret the location of sounds by filtering sounds from different directions - so-called ‘spectral cues’.
This ability to identify where sounds are coming from not only helps us to locate the path of moving objects but also helps us to separate different sound sources in noisy environments.
Glue ear, or otitis media, is a relatively common condition caused by a build-up of fluid in the middle ear that causes temporary hearing loss. By age 10, eight out of ten children will have experienced one or more episodes of glue ear. It usually resolves itself, but more severe cases can require interventions such as the insertion of tubes (commonly known as grommets) to drain the fluid and restore hearing.
If the loss of hearing is persistent, however, it can lead to impairments in later life, even after normal hearing has returned. These impairments include ‘lazy ear’, or amblyaudia, which leaves people struggling to locate sounds or pick out sounds in noisy environments such as classrooms or restaurants.
Researchers at the University of Oxford used removable earplugs to introduce intermittent, temporary hearing loss in one ear in young ferrets, mimicking the effects of glue ear in children. The team then tested their ability to localise sounds as adults and measured activity in the brain to see how the loss of hearing affected their development.
The results show that animals raised with temporary hearing loss were still able to localise sounds accurately while wearing an earplug in one ear. They achieved this by becoming more dependent on the unchanged spectral cues from the outer part of the unaffected ear. When the plug was removed and hearing returned to normal, the animals were just as good at localising sounds as those who had never experienced hearing loss.
Professor Andrew King, a Wellcome Trust Principal Research Fellow at the University of Oxford who led the study, explains: “Our results show that, with experience, the brain is able to shift the strategy it uses to localise sounds depending on the information that is available at the time.
"During periods of hearing loss in one ear - when the spatial cues provided by comparing the sounds at each ear are compromised - the brain becomes much more reliant on the intact spectral cues that arise from the way sounds are filtered by the outer ear. But when hearing is restored, the brain returns to using information from both ears to work out where sounds are coming from."
The results contrast with previous studies that looked at the effects of enduring hearing loss - rather than recurring hearing loss - on brain development. These earlier studies found that changes in the brain that result from loss of hearing persisted even when normal hearing returned.
The new findings suggest that intermittent experience of normal hearing is important for preserving sensitivity to those cues and could offer new strategies for rehabilitating people who have experienced hearing loss in childhood. In addition, the finding that spectral cues from the outer ear are an important source of information during periods of hearing loss has important implications for the design of hearing aids, particularly those that sit behind the ear.
"Recurring periods of hearing loss are extremely common during childhood. These findings will help us to find better ways of rehabilitating those affected, which should limit the number who go on to develop more serious hearing problems in later life," adds Professor King.
The study is published today in the journal ‘Current Biology’.
(Source: wellcome.ac.uk)
Alzheimer’s Disease Mouse Models Point To A Potential Therapeutic Approach
Building on research published eight years ago in the journal Chemistry and Biology, Kenneth S. Kosik, Harriman Professor in Neuroscience and co-director of the Neuroscience Research Institute (NRI) at UC Santa Barbara, and his team have now applied their findings to two distinct, well-known mouse models, demonstrating a new potential target in the fight against Alzheimer’s and other neurodegenerative diseases.
The results were published online June 4 as the Paper of the Week in the Journal of Biological Chemistry. As a Paper of the Week, Kosik’s work is among the top 2 percent of manuscripts the journal reviews in a year. Based on significance and overall importance, between 50 and 100 papers are selected for this honor from the more than 6,600 published each year.
Kosik and his research team focused on tau, a protein normally present in the brain, which can develop into neurofibrillary tangles (NFTs) that, along with plaques containing amyloid-ß protein, characterize Alzheimer’s disease. When tau becomes pathological, many phosphate groups attach to it, causing it to become dysfunctional and intensely phosphorylated, or hyperphosphorylated. Aggregations of hyperphosphorylated tau are also referred to as paired helical filaments.
"What struck me most while working on this project was how so many people I’d never met came to me to share their stories and personal anxieties about Alzheimer’s disease," said Xuemei Zhang, lead co-author and an assistant specialist in the Kosik Lab. "There is no doubt that finding therapeutic treatment is the only way to help this fast-growing population." Israel Hernandez, a postdoctoral scholar of the NRI and UCSB’s Department of Molecular, Cellular and Developmental Biology, is the paper’s other lead co-author.
Treatments for hyperphosphorylated tau, one of the main causes of Alzheimer’s disease, do not exist. Current treatment is restricted to drugs that increase the concentration of neurotransmitters to promote signaling between neurons.
However, this latest research explores the possibility that a small class of molecules called diaminothiazoles can act as inhibitors of kinase enzymes that phosphorylate tau. Kosik’s team studied the toxicity and immunoreactivity of several diaminothiazoles that targeted two key kinases, CDK5/p25 and GSK3ß, in two Alzheimer’s disease mouse models. The investigators found that the compounds can efficiently inhibit the enzymes with hardly any toxic effects in the therapeutic dose range.
Treatment with the lead compound in this study, LDN-193594, dramatically affected the prominent neuronal cell loss that accompanies increased CDK5 activity. Diaminothiazole kinase inhibitors not only reduced tau phosphorylation but also exerted a neuroprotective effect in vivo. In addition to reducing the amount of the paired helical filaments in the mice’s brains, they also restored their learning and memory abilities during a fear-conditioning assay.
According to the authors, the fact that treatment with diaminothiazole kinase inhibitors reduced the phosphorylation of tau provides strong evidence that small molecular kinase inhibitor treatment could slow the progression of tau pathology. “Given the contribution of both CDK5 and GSK3ß to tau phosphorylation,” said Kosik, “effective treatment of tauopathies may require dual kinase targeting.”
Madison Cornwell, a Beckman Scholar with UCSB’s Center for Science and Engineering Partnerships who worked in Kosik’s lab, added: “As a beginning step, we demonstrated that two of these compounds were successful in clearing the brain of tau tangles in a mouse model, but someday inhibitors of these kinases may serve to ameliorate the symptoms of Alzheimer’s disease in patients.”
Zebrafish study paves the way for new treatments for genetic disorder
Scientists from the University of Sheffield have paved the way for new treatments for a common genetic disorder thanks to pioneering research on zebrafish – an animal capable of mending its own heart.
Charcot Marie Tooth disease (CMT) is the most common genetic disorder affecting the nervous system. More than 20,000 people in the UK suffer from CMT, which typically causes progressive weakness and long-term pain in the feet, leading to walking difficulties. There is currently no cure for CMT.
A research project conducted at the Sheffield Institute for Translational Neuroscience (SITraN) and the MRC Centre for Developmental and Biomedical Genetics (CDBG) by Dr Andrew Grierson and his team has revealed that zebrafish could hold the key to finding new therapeutic approaches to treat the condition.
Dr Grierson said: “We have studied zebrafish with a genetic defect that causes CMT in humans. The fish develop normally, but once they reach adulthood they start to develop difficulties swimming.
"By looking at the muscles of these fish we have discovered that the problem lies with the connections between motor neurons and muscle, which are known to be essential for walking in humans and also swimming in fish."
CMT represents a group of neurodegenerative disorders typically characterised by demyelination (CMT1), a process which causes damage to the myelin sheaths that surround our neurons, or distal axon degeneration (CMT2) of motor and sensory neurons. The distal axon is the terminal where neurotransmitter packages within neurons are docked.
The majority of CMT2 cases are caused by mutations in mitofusin 2 (MFN2), which is an essential gene encoding a protein responsible for fusion of the mitochondrial outer membrane. Mitochondria are known as the cellular power plants because they generate most of the supply of adenosine triphosphate (ATP), which is used as a source of chemical energy.
Dr Grierson said: “Previous work on this disorder using mammalian models such as mice has been problematic, because the mitofusin genes are essential for embryonic development. Using zebrafish we were able to develop a model with an adult onset, progressive phenotype with predominant symptoms of motor dysfunction similar to CMT2.
"Motor neurons are the largest cells in our bodies, and as such they are highly dependent on a cellular transport system to deliver molecules through the long nerve cell processes which connect the spinal cord to our muscles. We already know that defects in the cellular transport system occur early in the development of diseases such as Alzheimer’s disease, Motor Neuron Disease and spastic paraplegia. Using our zebrafish model we have found that similar defects in transport are also a key part of the disease process in CMT."
Dr Grierson and his team are now seeking funding to identify new treatments for CMT using the zebrafish model. Because of their size and unique biology, zebrafish are ideal to be used in drug screens for the identification of new therapies for untreatable human conditions.
(Image courtesy: University College London)
Absence of Gene Leads to Earlier, More Severe Case of Multiple Sclerosis
A UC San Francisco-led research team has identified the likely genetic mechanism that causes some patients with multiple sclerosis (MS) to progress more quickly than others to a debilitating stage of the disease. This finding could lead to the development of a test to help physicians tailor treatments for MS patients.
Researchers found that the absence of the gene Tob1 in CD4+ T cells, a type of immune cell, was the key to early onset of more serious disease in an animal model of MS.
Senior author Sergio Baranzini, PhD, a UCSF associate professor of neurology, said the potential development of a test for the gene could predict the course of MS in individual patients.
The study, done in collaboration with UCSF neurology researchers Scott Zamvil, MD, and Jorge Oksenberg, PhD, was published on June 24 in the Journal of Experimental Medicine.
MS is an inflammatory disease in which the protective myelin sheathing that coats nerve fibers in the brain and spinal cord is damaged and ultimately stripped away – a process known as demyelination. During the highly variable course of the disease, a wide range of cognitive, debilitating and painful neurological symptoms can result.
In previously published work, Baranzini and his research team found that patients at an early stage of MS, known as clinically isolated syndrome, who expressed low amounts of Tob1 were more likely to exhibit further signs of disease activity – a condition known as relapsing-remitting multiple sclerosis – earlier than those who expressed normal levels of the gene.
The current study, according to Baranzini, had two goals: to recapitulate in an animal model what the researchers had observed in humans, and uncover the potential mechanism by which it occurs.
The authors were successful on both counts. They found that when an MS-like disease was induced in mice genetically engineered to be deficient in Tob1, the mice had significantly earlier onset compared with wild-type mice, and developed a more aggressive form of the disease.
Subsequent experiments revealed the probable cause: the absence of Tob1 in just CD4+ T cells. The scientists demonstrated this by transferring T cells lacking the Tob1 gene into mice that had no immune systems but had normal Tob1 in all other cells. They found that the mice developed earlier and more severe disease than mice that had normal Tob1 expression in all cells including CD4+.
“This shows that Tob1 only needs to be absent in this one type of immune cell in order to reproduce our initial observations in mice lacking Tob1 in all of their cells,” said Baranzini.
Personalized Treatments for MS Patients
The researchers also found the likely mechanism of disease progression in the Tob1-deficient mice: higher levels of Th1 and Th17 cells, which cause an inflammatory response against myelin, and lower levels of Treg cells, which normally regulate inflammatory responses. The inflammation results in demyelination.
The research is significant for humans, said Baranzini, because the presence or absence of Tob1 in CD4+ cells could eventually serve as a prognostic biomarker that could help clinicians predict the course and severity of MS in individual patients. “This would be useful and important,” he said, “because physicians could decide to switch or modify therapies if they know whether the patient is likely to have an aggressive course of disease, or a more benign course.”
Ultimately, predicted Baranzini, “This may become an example of personalized medicine. When the patient comes to the clinic, we will be able to tailor the therapy based on what the tests tell us. We’re now laying the groundwork for this to happen.”
(Source: ucsf.edu)
Dream of regenerating human body parts gets a little closer
Damage to vital organs, the spinal cord, or limbs can have an enormous impact on our ability to move, function – and even live. But imagine if you could restore these tissues back to their original condition and go on with life as normal.
Well, this is the dream for regenerative medicine. And while humans missed out on these abilities in the evolutionary lottery, a recent study in mice shows we’re making small progress to achieving this dream.
Learning from animals
Nature has provided the animal kingdom with many different ways to achieve perfect regeneration. Some amphibians – such as salamanders – are famous for their superhero-like ability to regenerate heart, brain, spinal cord, tail and can even whole limb tissue throughout their life.
Although organ and spinal cord regeneration are clinically important and worthy of intense research investment, regrowing whole limbs provides a flagship example of perfect regeneration in the salamander.
It has been known for more than a hundred years that if a salamander loses a limb, it grows right back. This process is extremely precise and removal of the limb at the shoulder regrows a full limb, but removal at the wrist only regrows the missing hand portion.
Interestingly, there does not seem to be a limit on how many times they can perform this clever trick and each time the limb comes back perfect.
But mammals (including humans and mice) seem to have missed out on this important skill. The question of how to enhance the regenerative capabilities in humans, either by adding the missing ingredients, or activating these latent abilities currently lies wide open.
Extending regeneration to mammals
Mammals currently only have the capacity to regenerate the very tip of their finger. But the result is far from perfect. A range of studies in mice have shown the digit-tip regrowth is severely restricted. Removal of the very tip of the mouse digit will be replaced, but removal of the tissue a small distance further up the digit and closer to nail bed (the equivalent to a human cuticle), will fail to regrow.
Last week, a group of researchers from the United States and Japan published work extending our understanding of the mechanism by which a resident stem cell population within the mouse digit tip nail bed can be activated to induce digit tip regeneration. In other words, we can now grow more of the digit back in mice and possibly more of the human finger.
Resident stem cells are specialised cells found at various locations within the body. When activated, these cells multiply and then transform into other cell types required to replace worn out cells under conditions of normal tissue maintenance.
This work builds on previous studies identifying the stem cell population in the nail bed by unveiling a signalling mechanism that could be exploited to enhance the amount of tissue that could be regrown. The potential for repair after injury appears very limited in many tissues and organs. Understanding how to enhance stem cell activation in these tissues may stimulate repair not previously thought possible.
The ability to switch on and mobilise resident stem cells in regeneration will be important in a wide range of new therapies, particularity for organs affected by injury or disease. On a world stage, momentum is currently growing for these types of strategies. It is clear that once refined, these approaches are sure to have a profound influence on many different aspects of clinical medicine, opening up the possibility of replacing diseased or injured tissues.
We may be some way off from the dream of replacing whole limbs in humans but recent progress confirms that by deepening our understanding of stem cell activation, we can directly unlock more regeneration in mammals than normally possible.
Compound enhances SSRI antidepressant’s effects in mice
A synthetic compound is able to turn off “secondary” vacuum cleaners in the brain that take up serotonin, resulting in the “happy” chemical being more plentiful, scientists from the School of Medicine at The University of Texas Health Science Center San Antonio have discovered. Their study, released June 18 by The Journal of Neuroscience, points to novel targets to treat depression.
Serotonin, a neurotransmitter that carries chemical signals, is associated with feelings of wellness. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that block a specific “vacuum cleaner” for serotonin (the serotonin transporter, or SERT) from taking up serotonin, resulting in more supply of the neurotransmitter in circulation in the extracellular fluid of the brain.
Delicate balance
"Serotonin is released by neurons in the brain," said Lyn Daws, Ph.D., professor of physiology and pharmacology in the School of Medicine. "Too much or too little may be a bad thing. It is thought that having too little serotonin is linked to depression. That’s why we think Prozac-type drugs (SSRIs) work, by stopping the serotonin transporter from taking up serotonin from extracellular fluid in the brain."
A problem with SSRIs is that many depressed patients experience modest or no therapeutic benefit. It turns out that, while SSRIs block the activity of the serotonin transporter, they don’t block other “vacuum cleaners.” “Until now we did not appreciate the presence of backup cleaners for serotonin,” Dr. Daws said. “We were not the first to show their presence in the brain, but we were among the first show that they were limiting the ability of the SSRIs to increase serotonin signaling in the brain. The study described in this new paper is the first demonstration of enhancing the antidepressant-like effect of an SSRI by concurrently blocking these backup vacuum cleaners.”
Serotonin ceiling
Even if SERT activity is blocked, the backup vacuum cleaners (called organic cation transporters) keep a ceiling on how high the serotonin levels can rise, which likely limits the optimal therapeutic benefit to the patient, Dr. Daws said.
"Right now, the compound we have, decynium-22, is not an agent that we want to give to people in clinical trials," she said. "We are not there yet. Where we are is being able to use this compound to identify new targets in the brain for antidepressant activity and to turn to medicinal chemists to design molecules to block these secondary vacuum cleaners."
(Source: eurekalert.org)
Animal study shows promising path to prevent epilepsy
Duke Medicine researchers have identified a receptor in the nervous system that may be key to preventing epilepsy following a prolonged period of seizures.
Their findings from studies in mice, published online in the journal Neuron on June 20, 2013, provide a molecular target for developing drugs to prevent the onset of epilepsy, not just manage the disease’s symptoms.
"Unfortunately, there are no preventive therapies for any common disorder of the human nervous system – Alzheimer’s, Parkinson’s, schizophrenia, epilepsy – with the exception of blood pressure-lowering drugs to reduce the likelihood of stroke," said study author James O. McNamara, M.D., professor of neurobiology at Duke Medicine.
Epilepsy is a serious neurological disorder marked by recurring seizures. Temporal lobe epilepsy – where seizures occur in the region of the brain where memories are stored and language, emotions and senses are processed – is the most common form, and can be devastating. Because afflicted individuals have seizures that impair their awareness and may have associated behavioral problems, they may have difficulty with everyday activities, including holding a job or obtaining a driver’s license.
Conventional therapies to treat epilepsy address the disease’s symptoms by trying to reduce the likelihood of having a seizure. However, many people with temporal lobe epilepsy still have seizures despite taking these drugs.
"This study opens a promising new avenue of research into treatments that may prevent the development of epilepsy," said Vicky Whittemore, PhD, a program director at the National Institute of Neurological Disorders and Stroke, who oversees the grants that funded this study.
Retrospective studies of people with severe temporal lobe epilepsy reveal that many of them initially have an episode of prolonged seizures, known as status epilepticus. Status epilepticus is often followed by a period of seizure-free recovery before people start to experience recurring temporal lobe seizures.
In animal studies, inducing status epilepticus in an otherwise healthy animal can cause them to become epileptic. The prolonged seizures in status epilepticus are therefore thought to cause or importantly contribute to the development of epilepsy in humans.
"An important goal of this field has been to identify the molecular mechanism by which status epilepticus transforms a brain from normal to epileptic," said McNamara. "Understanding that mechanism in molecular terms would provide a target with which one could intervene pharmacologically, perhaps to prevent an individual from becoming epileptic."
Earlier research in epilepsy flagged a receptor in the nervous system called TrkB as a key player in transforming the brain from normal to epileptic. In the current study, McNamara and his colleagues sought to confirm if TrkB was important for status epilepticus-induced epilepsy.
Using an approach combining chemistry and genetic analyses, the researchers studied normal and genetically altered mice. The genetically altered mice were unique in that a drug, 1NMPP1, inhibited TrkB in their brains. If the drug stopped the genetically altered mice from becoming epileptic, this genetic approach would prove that inhibiting TrkB prevents the onset of epilepsy.
When the researchers caused status epilepticus in the animals, both the normal and genetically modified mice developed epilepsy. However, treatment with 1NMPP1 after the prolonged period of seizures prevented epilepsy in the genetically altered but not the normal mice.
"This demonstrated that it is possible to intervene following status epilepticus and prevent the animal from becoming epileptic," McNamara said.
Importantly, the researchers only administered treatment with 1NMPP1 for two weeks, which was sufficient to prevent epilepsy from developing in the mice when tested many weeks later. The results suggest that a preventive therapy may only need to be given for a limited period of time following the initial bout of prolonged seizures, not an individual’s entire life, which could prevent unnecessary side effects that come with long-term use of drugs.
In future studies, the researchers hope to determine the exact time window in which TrkB signaling needs to be repressed to prevent the onset of epilepsy. Long term, this research provides a molecular target for developing the first drugs to prevent epilepsy.
"This study provides a strong rationale for the development of selective inhibitors of TrkB signaling," said McNamara.
New virus isolated from patients with severe brain infections
Researchers have identified a new virus in patients with severe brain infections in Vietnam. Further research is needed to determine whether the virus is responsible for the symptoms of disease.
The virus was found in a total of 28 out of 644 patients with severe brain infections in the study, corresponding to around 4 per cent, but not in any of the 122 patients with non-infectious brain disorders that were tested.
Infections of the brain and central nervous system are often fatal, and patients who survive - often young children and young adults - are left severely disabled. Brain infections can be caused by a range of bacterial, parasitic, fungal and viral agents; however, doctors fail to find the cause of the infection in more than half of all cases, despite extensive diagnostic efforts. Not knowing the causes of these brain infections makes public health and treatment interventions impossible.
Researchers at the Oxford University Clinical Research Unit, the Wellcome Trust South East Asia Major Overseas Programme and the Academic Medical Center at the University of Amsterdam identified the virus, tentatively named CyCV-VN, in the fluid around the brain of two patients with brain infections of unknown cause. The virus was subsequently detected in an additional 26 out of 642 patients with brain infections of known and unknown causes.
Using next-generation gene sequencing techniques, the team sequenced the entire genetic material of the virus, confirming that it represents a new species that has not been isolated before. They found that it belongs to a family of viruses called the Circoviridae, which have previously only been associated with disease in animals, including birds and pigs.
Dr Rogier van Doorn, Head of Emerging Infections at the Wellcome Trust Vietnam Research Programme and Oxford University Clinical Research Unit Hospital for Tropical Diseases in Vietnam, explains: “We don’t yet know whether this virus is responsible for causing the serious brain infections we see in these patients, but finding an infectious agent like this in a normally sterile environment like the fluid around the brain is extremely important. We need to understand the potential threat of this virus to human and animal health.”
The researchers were not able to detect CyCV-VN in blood samples from the patients, but it was present in 8 out of 188 faecal samples from healthy children. The virus was also detected in more than half of faecal samples from chickens and pigs taken from the local area of one of the patients from whom the virus was initially isolated, which may suggest an animal source of infection.
Dr Le Van Tan, Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, said: “The evidence so far seems to suggest that CyCV-VN may have crossed into humans from animals, another example of a potential zoonotic infection. However, detecting the virus in human samples is not in itself sufficient evidence to prove that the virus is causing disease, particularly since the virus could also be detected in patients with other known viral or bacterial causes of brain infection.
"While detection of this virus in the fluid around the brain is certainly remarkable, it could still be that it doesn’t cause any harm. Clearly, we need to do more work to understand the role this virus may play in these severe infections."
The researchers are currently trying to grow the virus in the laboratory using cell culture techniques to develop a blood assay to test for antibody responses in patient samples, which would indicate that the patients had mounted an immune response against the virus. Such a test could also be used to study how many people in the population have been exposed to CyCV-VN without showing symptoms of disease.
The team are collaborating with scientists across South-east Asia and in the Netherlands to determine whether CyCV-VN can be detected in patient samples from other countries and better understand its geographical distribution.
Professor Menno de Jong, head of the Department of Medical Microbiology of the Academic Medical Centre in Amsterdam, said: “Our research shows the importance of continuing efforts to find novel causes of important infectious diseases and the strength of current technology in aid of these efforts.”
(Source: wellcome.ac.uk)
Study Shows How the Nanog Protein Promotes Growth of Head and Neck Cancer
A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) has identified a biochemical pathway in cancer stem cells that is essential for promoting head and neck cancer.
The study shows that a protein called Nanog, which is normally active in embryonic stem cells, promotes the growth of cancer stem cells in head and neck cancer. The findings provide information essential for designing novel targeted drugs that might improve the treatment of head and neck cancer.
Normally, Nanog helps healthy embryonic stem cells maintain their undifferentiated, uncommitted (i.e., pluripotent) state. But recent evidence suggests that Nanog promotes tumor growth by stimulating the proliferation of cancer stem cells.
“This study defines a signaling axis that is essential for head and neck cancer progression, and our findings show that this axis may be disrupted at three key steps,” says principal investigator Quintin Pan, PhD, associate professor of otolaryngology at the OSUCCC – James. “Targeted drugs that are designed to inhibit any or all of these three steps might greatly improve the treatment of head and neck cancer.”
The findings were published in a recent issue of the journal Oncogene.
Specifically, the study shows that an enzyme called “protein kinase C-epsilon” (PKCepsilon) adds energy-packing phosphate groups to the Nanog molecule. This phosphorylation of Nanog stabilizes and activates the molecule.
It also triggers a series of events: Two Nanog molecules bind together, and these are joined by a third “co-activating” molecule called p300. This molecular complex then binds to the promoter region of a gene called Bmi1, an event that increases the expression of the gene. This, in turn, stimulates proliferation of cancer stem cells.
“Our work shows that the PKCepsilon/Nanog/Bmi1 signaling axis is essential to promote head and neck cancer,” Pan says. “And it provides initial evidence that the development of inhibitors that block critical points in this axis might yield a potent collection of targeted anti-cancer therapeutics that could be valuable for the treatment of head and neck cancer.”
(Image: Gray’s Anatomy of the Human Body)