Underexpressed Protein May Play Role in Down Syndrome
Contrary to conventional wisdom that the symptoms of Down syndrome are likely caused by an overabundance of certain proteins due to the additional copy of chromosome 21, scientists at Ohio State University and collaborators have found evidence that at least some of the symptoms may actually be associated with underexpression of a certain protein or proteins due to the presence of five microRNA genes on chromosome 21. MicroRNAs bind to messenger RNA and cause the inhibition of protein synthesis for that messenger RNA. Computer analysis revealed over 1,600 proteins that were potential targets of the five microRNAs on chromosome 21, all of which could cause problems in Down syndrome because they would be underexpressed. Based on other evidence, the researchers selected one of the protein genes (for methyl-CpG-binding protein 2, known as MeCP2) for further study. Among the reasons for selecting this gene was that it is known to be mutated in Rett syndrome, an inherited cognitive disorder. The researchers used just two of the five microRNAs on chromosome 21 for the experiments in this study, miR-155 and miR-802, to match the only microRNAs available in the genetically engineered mouse model of Down syndrome. First, the researchers made copies of the relevant microRNAs. In human brain cell lines, they manipulated levels of those two molecules to show the inverse relationship with MeCP2. If the microRNAs were overexpressed, the level of the MeCP2 protein went down. When the microRNAs were underexpressed, the protein levels went up.
Next, the researchers examined adult and fetal human brain tissue from healthy and Down syndrome samples obtained from a national tissue bank. “In both adult and fetal Down syndrome brain samples, it didn’t matter which area of the brain we were looking at, the MeCP2 proteins were down. These are just observations with no manipulation on our part, and the MeCP2 is almost non-existent in the Down syndrome brain,” senior author Dr. Terry Elton said. “We marked the protein with a fluorescent molecule, and by comparison, we could visualize and appreciate how much MeCP2 was being made by neurons in the control samples.”
MeCP2 is a transcription factor, meaning that it turns genes on and off. If its levels are too low in the brain, this suggests that genes influenced by its presence should be malfunctioning too. Based on previous research by another group, Dr. Elton and colleagues focused on two genes affected by the MeCP2 protein for their next set of experiments. Looking again at the human brain tissue samples, they found that the genes were indeed affected by the lowered protein level in Down syndrome brains--one gene that MeCP2 normally silences was in abundance, and the gene that should have been activated was underexpressed. Because the two genes examined have known roles in neural development, Dr. Elton said the results suggested even more strongly that the lowered protein’s effects on the genes likely contribute to cognitive problems associated with Down syndrome.
Finally, the researchers tested an experimental drug called an antagomir on mice that serve as models for Down syndrome research. Antagomirs are relatively new agents that render microRNAs inactive. The scientists injected an antagomir into the brains of these mice to silence the miR-155 with the intent to increase levels of the MeCP2 protein. Seven days after the injection, the level of the protein in the treated mouse brains resembled levels in normal mouse brains. “We showed that we can fix the protein abnormality in mice that model Down syndrome. But we can’t undo the pathology that has already occurred,” Elton said. “It’s a starting point, but it appears that we have new therapeutic targets to consider.”
This work was published in the January 8, 2010 issue of the Journal of Biological Chemistry.
April 02, 2010
Older Unsupported Women More Likely to have Heart Failure with Preserved Systolic Function
Older women who have less social support and live in nursing homes are more likely to have heart failure with preserved systolic function than those who are married or living in their own home, according to the results of research published in the Medical Journal of Australia.
Dr Sepehr Shakib, from the Royal Adelaide Hospital, and his co-authors, including cardiologists Dr Dennis Wong and Dr Ben Dundon with social epidemiologist Dr Robyn Clark from the Samson Institute, University of South Australia, undertook a retrospective analysis of clinical data for 2961 patients admitted with chronic heart failure over a period of 10 years.
The authors found patients who had heart failure with preserved systolic function (HFPSF) were predominantly older women with less social support and a greater burden of comorbid conditions such as renal impairment, anaemia and atrial fibrillation compared with those with left ventricular systolic dysfunction.
There was also an increase in the risk of re-hospitalisation among patients with HFPSF. Dr Shakib said lack of social and carer support and a greater burden of comorbid conditions in patients with HFPSF may have played a significant predisposing role in hospitalisation and readmissions. "Our study is the first to identify significant differences in the social environment of these patients," Dr Shakib said.
"We propose that the burden of reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management."
January 19, 2010
Running in Shoes Stresses Hips, Knees and Ankles More Than Running Barefoot, Study
Researchers in the US who compared the effects on hip, knee and ankle joints of running barefoot versus running in modern running shoes, concluded that running in shoes exerted more stress on these joints compared to running barefoot or even walking in high-heeled shoes.
The study was the work of lead author Dr D Casey Kerrigan, of JKM Technologies LLC, in Charlottesville, Virginia and colleagues from the University of Colorado and the University of Virginia, and was published in the December 2009 issue of PM&R: The journal of injury, function and rehabilitation.
Knee osteoarthritis (OA) accounts for more disability in the elderly than any other disease, and although running has been shown to benefit health in many ways, including cardiovascular health, it can stress the joints in the leg, such as the hip, knee, and ankle.
January 19, 2010
New Key Factor Identified in the Development of Alzheimer's disease
Inheritance of an extra copy of the gene - beta - amyloid precursor protein, APP, in individuals with Down syndrome leads to the inevitable development of early onset Alzheimer's disease, known to be linked to the deposition of Amyloid beta peptide or A beta in the brain. However, a new study published online by Proceedings of the National Academy of Sciences identifies betaCTF, a small protein found in APP, as a novel factor for the development of Alzheimer's disease related endosome abnormalities, which have also been tied previously to the loss of brain cells in Alzheimer's disease.
"In the study, using the cells from individuals with Down syndrome that are genetically predisposed to developing Alzheimer's disease, we showed that elevated levels of ßCTF, independent of Aß, cause a specific pattern of endosome defects with similar pathology of brain cells in Alzheimer's disease," said Ying Jiang, PhD, lead author and clinical instructor in the Department of Psychiatry at NYU Langone Medical Center. "Our research was successfully able to pinpoint that ßCTF causes Alzheimer's disease -related endosome defects and that we could successfully reverse these endosome defects by lowering ßCTF levels in the cells."
January 19, 2010
THT Launches LearningPlus - A New Service to Help People with HIV in England Become Experts in Their Condition
Terrence Higgins Trust (THT) has been awarded £70,000 from the Department for Innovation Universities and Skills (DIUS) for a new project called LearningPlus. The grant will be used for people living with HIV to become Positive Self-Management Programme (PSMP) Lead Trainers or PSMP Facilitators. The Lead Trainers and Facilitators will go on to deliver PSMP courses to help people with HIV across England to become experts in their own condition. The LearningPlus training opportunities will commence from January until March next year.
LearningPlus aims to empower people living with HIV to take more control of their health. The course will address issues including relaxation techniques, exercise, healthy eating, dealing with depression, communicating with family, friends and health professionals, as well as planning for the future. The classes also provide an ideal opportunity to meet other people with HIV and share experiences - and are a great way to build confidence and take control.
January 19, 2010
Join the NHS Organ Donor Register, UK
NHS Blood and Transplant (NHSBT) urges UK citizens to make a positive, outward-looking resolution: join the NHS Organ Donor Register (ODR) and help make a real difference to the 10,000 patients in the United Kingdom who need an organ transplant. Online and phone sign-ups to the ODR quadrupled1 in November 2009 compared to the same month in 2008 - yet more must be done, with 3 people dying every day while they wait for an organ to become available.
The most popular New Year resolutions are focused on self-improvement, and are often unfulfilled: to eat more fruit and vegetables, do more exercise, stop smoking, and drink less alcohol.2 But we can do one very achievable simple thing focusing on saving the lives of others - join the NHS Organ Donor Register.
The increase is a result of NHSBT's first-ever UK public awareness campaign for organ donation, encouraging more than 112,0003 people in the first month to join the ODR.
Of these, over 34,000 signed up by going online with the most common age group being 16-34 year olds, and 60% of online registrations coming from women. Over-55s accounted for 10% of the sign-ups. Regionally, the greatest number of online sign-ups during November 2009 came from the North West of England - 3,994 - while the highest proportion of registrations came from the North East of England - 736 per million population. The biggest increase over the same month last year (over 5-fold) was seen in Northern Ireland, followed by South West of England (a 462% increase).
January 19, 2010
In The New Year, Get Fit, Don't Get Hurt
Life is full of hassles, deadlines, frustrations and demands. Stress can take its toll on a woman's health and spill into the home during the holiday season. In these economic times, tightening budgets during the 'season to be jolly' brings additional stress. There is hope on the horizon, as the New Year provides a fresh opportunity for women to resolve to get a handle on stress.
"If time or finances prohibit you from going to the gym, find other ways to stay active such as taking a walk, running and even yard work or gardening."
"It is very important to set fitness goals and incorporate physical activity into your daily routine to manage stress levels," says NYC physical therapist Megan Barclay. "If time or finances prohibit you from going to the gym, find other ways to stay active such as taking a walk, running and even yard work or gardening."
Chronic stress can lead to serious health problems including elevated blood pressure, a suppressed immune system, increased risk of heart attack, contribute to infertility and accelerate the aging process, to name a few. So it is important to recognize when your stress levels are out of control and make a resolution to regain control of your health.
Barclay says, "The most dangerous aspect of stress is how easily it can creep up on you, it can start to feel familiar and even normal. You don't notice how much of an effect it has on you, even as it takes a heavy burden on your body."
While well-intentioned, most New Year's resolutions to get in shape involve beginning a fitness regimen characterized by over-exertion and strenuous exercise, and many women wind up suffering from injuries - most commonly to their knees and ankles. Those trouble areas should be supported, but most women find the braces and supports on the market do not fit well or are uncomfortable. There is a reason for this.
January 19, 2010
Earlier Bedtimes May Help Protect Adolescents against Depression and Suicidal Thoughts
A study in the Jan. 1 issue of the journal Sleep found that adolescents with bedtimes that were set earlier by parents were significantly less likely to suffer from depression and to think about committing suicide, suggesting that earlier bedtimes could have a protective effect by lengthening sleep duration and increasing the likelihood of getting enough sleep.
Results show that adolescents with parental set bedtimes of midnight or later were 24 percent more likely to suffer from depression (odds ratio = 1.24) and 20 percent more likely to have suicidal ideation (OR=1.20) than adolescents with parental set bedtimes of 10 p.m. or earlier. This association was appreciably attenuated by self-reported sleep duration and the perception of getting enough sleep. Adolescents who reported that they usually sleep for five or fewer hours per night were 71 percent more likely to suffer from depression (OR=1.71) and 48 percent more likely to think about committing suicide (OR=1.48) than those who reported getting eight hours of nightly sleep. Participants who reported that they "usually get enough sleep" were significantly less likely to suffer from depression (OR=0.35) and suicidal ideation (OR=0.71).
January 19, 2010
Unusual Protein Modification Involved in Muscular Dystrophy, Cancer
With the discovery of a new type of chemical modification on an important muscle protein, a University of Iowa study improves understanding of certain muscular dystrophies and could potentially lead to new treatments for the conditions.
The findings, which appear in the Jan. 1, 2010, issue of the journal Science, may also have implications for detecting metastasizing cancer cells.
After they are initially made, most proteins are modified through the addition of sugar chains, fats or other chemical groups. These modifications can completely change how a protein works and where it is located in the body. Disruption of these modifications can alter protein function, too, and can lead to disease.
The UI study focused on dystroglycan, a cell membrane protein that is disrupted in many forms of muscular dystrophy. Normal dystroglycan is modified with a unique sugar chain that allows the protein to "glue" muscle membranes to the basal lamina -- a tough layer of extracellular proteins. This arrangement reinforces the fragile muscle membrane and prevents small tears that occur naturally from expanding and damaging the membrane.
Recent work, including studies by the UI team, show that disrupting dystroglycan's ability to attach to the basal lamina causes congenital muscular dystrophies and also leads to cancer progression in epithelial cell cancer. In these conditions, the dystroglycan sugar chain is incompletely or incorrectly assembled and the dystroglycan cannot bind tightly to laminin.
"Dystroglycan is a complex and unusual glycoprotein. It is heavily covered with many types of sugars. We wanted to know the shape and make up of the unique sugar chain that allows dystroglycan to bind to laminin," said study leader Kevin Campbell, Ph.D., professor and head of molecular physiology and biophysics at the UI Roy J. and Lucille A. Carver College of Medicine and a Howard Hughes Medical Institute investigator.
January 19, 2010
Bigger Role for GPs Needed in Identifying and Treating Hearing Loss, Australia
General Practitioners should play a bigger role in the detection and treatment of age-related hearing loss, according to an article published in the Medical Journal of Australia. Prof Paul Mitchell, of the Westmead Millennium Institute at the University of Sydney, and his co-authors analysed data collected between 1998 and 2000 from the Blue Mountains Hearing Study (BMHS) and between 2003 and 2008 as part of the Bettering the Evaluation and Care of Health (BEACH) study.
Of people aged over 50 years in the Blue Mountains study with bilateral hearing loss, about one third reported seeking help from their GP.
"In their routine consultations with patients, GPs have opportunities to identify hearing loss and appropriately refer patients to specialists or allied health professionals," Prof Mitchell said.
GPs responded to patient presentations for hearing loss, referring about 50 per cent of cases to specialists or allied health professionals. But they appeared to identify relatively few cases of hearing loss opportunistically.
Biofilms: Researchers Discover New Ways to Treat Chronic Infections
Researchers at Binghamton University, State University of New York, have identified three key regulators required for the formation and development of biofilms. The discovery could lead to new ways of treating chronic infections.
Biofilms -- commu... more
April 07, 2010
Keeping Hepatitis C Virus at Bay After a Liver Transplant
One of the most common reasons for needing a liver transplant is liver failure or liver cancer caused by liver cell infection with hepatitis C virus (HCV). However, in nearly all patients the new liver becomes infected with HCV almost immediately.