Posts tagged science
Articles and news from the latest research reports.
Combination of imaging exams improves Alzheimer’s diagnosis
A combination of diagnostic tests, including imaging and cerebrospinal fluid biomarkers can improve prediction of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, according to a new study published online in the journal Radiology.
"Because new treatments are likely to be most effective at the earliest stages of Alzheimer’s disease, there is great urgency to develop sensitive markers that facilitate detection and monitoring of early brain changes in individuals at risk," said Jeffrey R. Petrella, M.D., associate professor of radiology, division of neuroradiology, and director of the Alzheimer’s Disease Research Lab at Duke University Medical Center (DUMC) in Durham, N.C. "Our study looks at whether more sophisticated diagnostic tests such as magnetic resonance imaging (MRI), positron emission tomography (PET) and spinal fluid protein analysis might provide additional prognostic information, compared to more readily available cognitive and blood testing."
According to the World Health Organization, more than 35 million people worldwide are living with Alzheimer’s disease, which is incurable, and the prevalence is expected to double by 2030.
"Although there is no cure for Alzheimer’s disease, there are four symptomatic treatments that might provide some benefits," said coauthor P. Murali Doraiswamy, M.D., professor of psychiatry at DUMC. "So developing the right combination of diagnostic tests is critical to make sure we enable an accurate and early diagnosis in patients, so they can evaluate their care options."
Neuroscience: Under Attack
This fall, science writers have made sport of yet another instance of bad neuroscience. The culprit this time is Naomi Wolf; her new book, “Vagina,” has been roundly drubbed for misrepresenting the brain and neurochemicals like dopamine and oxytocin.
Earlier in the year, Chris Mooney raised similar ire with the book “The Republican Brain,” which claims that Republicans are genetically different from — and, many readers deduced, lesser to — Democrats. “If Mooney’s argument sounds familiar to you, it should,” scoffed two science writers. “It’s called ‘eugenics,’ and it was based on the belief that some humans are genetically inferior.”
Sharp words from disapproving science writers are but the tip of the hippocampus: today’s pop neuroscience, coarsened for mass audiences, is under a much larger attack.
Meet the “neuro doubters.” The neuro doubter may like neuroscience but does not like what he or she considers its bastardization by glib, sometimes ill-informed, popularizers.
Anatomical Brain Images Alone Can Accurately Diagnose Chronic Neuropsychiatric Illnesses
Objective
Diagnoses using imaging-based measures alone offer the hope of improving the accuracy of clinical diagnosis, thereby reducing the costs associated with incorrect treatments. Previous attempts to use brain imaging for diagnosis, however, have had only limited success in diagnosing patients who are independent of the samples used to derive the diagnostic algorithms. We aimed to develop a classification algorithm that can accurately diagnose chronic, well-characterized neuropsychiatric illness in single individuals, given the availability of sufficiently precise delineations of brain regions across several neural systems in anatomical MR images of the brain.
Methods
We have developed an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. The method employs a semi-supervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions. We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.
Results
In MRI datasets from persons with Attention-Deficit/Hyperactivity Disorder, Schizophrenia, Tourette Syndrome, Bipolar Disorder, or persons at high or low familial risk for Major Depressive Disorder, our method discriminated with high specificity and nearly perfect sensitivity the brains of persons who had one specific neuropsychiatric disorder from the brains of healthy participants and the brains of persons who had a different neuropsychiatric disorder.
Conclusions
Although the classification algorithm presupposes the availability of precisely delineated brain regions, our findings suggest that patterns of morphological variation across brain surfaces, extracted from MRI scans alone, can successfully diagnose the presence of chronic neuropsychiatric disorders. Extensions of these methods are likely to provide biomarkers that will aid in identifying biological subtypes of those disorders, predicting disease course, and individualizing treatments for a wide range of neuropsychiatric illnesses.
Trabecular meshwork cells from a pig’s eye
Image by Carmen Laethem (Aerie Pharmaceuticals Research Triangle Park, North Carolina, USA)
(Source: nikonsmallworld.com)
How Different Nerve Cells Develop in the Eye
Neurobiologists from Heidelberg University’s Centre for Organismal Studies (COS) have gained new insights into how different types of nerve cells are formed in the developing animal. Through specialised microscopes, they were able to follow the development of the neural retina in the eye of living zebrafish embryos. Using high-resolution three-dimensional time-lapse images the researchers simultaneously observed the division of retinal nerve cells and changes in gene expression. This enabled them to gain insights into the way in which the two processes are linked during eye development and how the number and proportion of different cell types are regulated.
A central question in developmental and regenerative neurobiology concerns the growth processes in animal organisms: How does a growing animal control the generation of the right number of each type and subtype of nerve cell in the brain and what is the relationship between these cells? The retina consists of many different kinds of nerve cells, which are well characterised and common to all vertebrates. Thus, the retina is a particularly good model for studying neuronal development. The researchers studied such retinal developmental processes in living organisms using zebrafish embryos, which are completely transparent and grow rapidly outside their mother.
All retinal cells, which are either excitatory or inhibitory, arise from a relatively small number of apparently homogeneous progenitor cells. These progenitors are able to generate all the different retinal cell types. “It is a challenge to understand how each progenitor cell contributes to the correct number and subtype of nerve cells that compose the final retinal network. Our work contributes to the understanding of how different genes orchestrate neuronal diversity along a progenitor cell lineage, that is the number of cell divisions and types of neurons generated”, says Heidelberg researcher Dr. Lucia Poggi.
To tackle this challenge, Dr. Poggi’s team used different lines of transgenic zebrafish, in which fluorescent reporter proteins highlight the expression of different genes in dividing cells. Working in close cooperation with Dr. Patricia Jusuf of the Australian Regenerative Medicine Institute at Monash University, the researchers found that some particular kinds of excitatory and inhibitory nerve cells tend to be lineally related, i.e. they derive from a common progenitor cell. For the first time, 4D recordings permitted an in vivo analysis of how the generation of particular inhibitory cells is regulated through coordination of cell division mode and gene expression within individual retinal progenitors of excitatory nerve cells.
This study has established a model of how cell lineage influences neuronal subtype specification and neuronal circuitry formation in the native environment of the vertebrate brain. The results were published in the Journal of Neuroscience.
(Source: uni-heidelberg.de)
The Case for Drinking as Much Coffee as You Like
"What I tell patients is, if you like coffee, go ahead and drink as much as you want and can," says Dr. Peter Martin, director of the Institute for Coffee Studies at Vanderbilt University. He’s even developed a metric for monitoring your dosage: If you are having trouble sleeping, cut back on your last cup of the day. From there, he says, "If you drink that much, it’s not going to do you any harm, and it might actually help you. A lot."
Officially, the American Medical Association recommends conservatively that “moderate tea or coffee drinking likely has no negative effect on health, as long as you live an otherwise healthy lifestyle.” That is a lackluster endorsement in light of so much recent glowing research. Not only have most of coffee’s purported ill effects been disproven — the most recent review fails to link it the development of hypertension — but we have so, so much information about its benefits. We believe they extend from preventing Alzheimer’s disease to protecting the liver. What we know goes beyond small-scale studies or limited observations. The past couple of years have seen findings, that, taken together, suggest that we should embrace coffee for reasons beyond the benefits of caffeine, and that we might go so far as to consider it a nutrient.
The most recent findings that support coffee as a panacea will make their premiere this December in the American Journal of Clinical Nutrition. Coffee, researchers found, appears to reduce the risk of type 2 diabetes.
Would you make your DNA and health data public if it may help cure disease?
The 39-year-old Toronto professional is the brave or, perhaps, foolhardy Canadian volunteer who will be first to go public this week in a project that will reveal the coded secrets hidden in her genome, the six billion chemical units of her DNA.
They may include not only her susceptibility to diseases such as cancer but the levels of her propensities to alcoholism, depression or obesity, or even personality traits such as risk-taking. She will also provide the personal context required to make sense of the biological data – her age, height, weight; medical records; details about how she lives, works and plays; and even her photo if she’s game.
This information – everything but her name and address – will be placed on an online database that will be open and available to anyone in the world. Even in this digital age of perpetual show and tell, exposing oneself so completely amounts to a molecular full monty: Even without a name attached, any participant might be identifiable.
Ms. Davies is making a leap of faith that at least 100,000 of her fellow citizens are also being asked to take – even though Canadian law has no strict guidelines on how this confidential knowledge might be used or misused by any insurance company, employer, police force or identity thief.
Britain launches genome database for patients’ DNA
Up to 100,000 Britons suffering from cancer and rare diseases are to have their genetic codes fully sequenced and mapped as part of government plans to build a DNA database to boost drug discovery and development.
Prime Minister David Cameron said on Monday he wanted Britain to “push the boundaries” of scientific research by being the first country to introduce genetic sequencing into a mainstream health service.
His government has set aside 100 million pounds ($160 million) for the project in the taxpayer-funded National Health Service (NHS) over the next three to five years.
"Britain has often led the world in scientific breakthroughs and medical innovations, from the first CT scan and test-tube baby through to decoding DNA," he said in a statement.
"It is crucial that we continue to push the boundaries and this new plan will mean we are the first country in the world to use DNA codes in the mainstream of the health service."
The government said building a database of DNA profiles will give doctors more advanced understanding of a patient’s genetic make-up, their illness and their treatment needs. This should help those who are sick get access to the right drugs and more personalized care more quickly.
The database should also help scientists develop new drugs and other treatments which experts predict “could significantly reduce the number of premature deaths from cancer within a generation”, Cameron’s office said in a statement,
"By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care," Cameron said.
"If we get this right, we could transform how we diagnose and treat our most complex diseases not only here but across the world, while enabling our best scientists to discover the next wonder drug or breakthrough technology."
Turning urine into brain cells
Chinese researchers have devised a new technique for reprogramming cells from human urine into immature brain cells that can form multiple types of functioning neurons and glial cells. The technique, published in the journal Nature Methods, could prove useful for studying the cellular mechanisms of neurodegenerative conditions such as Alzheimer’s and Parkinson’s and for testing the effects of new drugs that are being developed to treat them.
Stem cells offer the hope of treating these debilitating diseases, but obtaining them from human embryos poses an ethical dilemma. We now know that cells taken from the adult human body can be made to revert to a stem cell-like state and then transformed into virtually any other type of cell. This typically involves using genetically engineered viruses that shuttle control genes into the nucleus and inserts them into the chromosomes, whereupon they activate genes that make them pluripotent, or able to re-differentiate into another type of cell.
In 2008, for example, American researchers took skin cells from an 82-year-old patient with amyotrophic lateral sclerosis and reprogrammed them into motor neurons. Cells obtained in this way could help us gain a better understanding of such diseases. Grafts of patients’ own cells do not elicit an immune response, so this approach may eventually lead to effective cell transplantation therapies. But it also has its problems – it appears that the reprogramming process destabilizes the genome and causes mutations, and that iPSCs may therefore harbour genetic defects that render them useless.
Last year, Duanqing Pei of the Chinese Academy of Sciences and his colleagues reported that human urine contains skin-like cells from the lining of the kidney tubules which can be efficiently reprogrammed, via the pluripotent state, into neurons, glia, liver cells and heart muscle cells. Now they have improved on the approach, making it quicker, more efficient and possibly less prone to errors.
In the new study, they isolated cells from urine samples given by three donors, aged 10, 25 and 37, and converted them directly into neural progenitors. They then grew these cells in Petri dishes and drove them to differentiate into mature neurons that can generate nervous impulses, and also into astrocytes and oligodendrocytes, two types of glial cell found in the human brain. Finally, they transplanted the re-programmed neurons and astrocytes into the brains of newborn rats, and found that the cells had survived when they examined the brains a month later, but it remains to be seen if they can survive for longer, and if they integrate into the existing circuits to be become functional.
This isn’t the first time that one type of cell has been converted into another without going through the pluripotent stage – in 2010, researchers from Stanford converted mouse connective tissue cells directly into neurons. The new technique does have a number of advantages, however.
Instead of using a virus to deliver the reprogramming genes, the researchers used a small circular piece of bacterial DNA which can replicate in the cytoplasm. This not only speeds up the process, but also eliminates the need to integrate the reprogramming genes into the chromosome, which is one potential source of genetic mutation, but it’s still not clear whether these cells contain fewer mutations than those reprogrammed using viruses.
Even so, the technique also makes the procedure of generating iPSCs far easier and non-invasive, as the cells can be obtained from a urine sample instead of a blood sample or biopsy. The next logical step will be to generate neurons from urine samples obtained from patients with Alzheimer’s, Parkinson’s, and other neurodegenerative diseases and to determine the extent to which this new non-viral technique damages the DNA.
(Source: Guardian)
In an article published online this week in the journal Nature, the UCSF team has identified the exact subset of nerve cells responsible for communicating gentle touch to the brains of Drosophila larvae—called class III neurons. They also uncovered a particular protein called NOMPC, which is found abundantly at the spiky ends of the nerves and appears to be critical for sensing gentle touch in flies.Without this key molecule, the team discovered, flies are insensitive to any amount of eyelash stroking, and if NOMPC is inserted into neurons that cannot sense gentle touch, those neurons gain the ability to do so.
“NOMPC is sufficient to confer sensitivity to gentle touch,” said Yuh Nung Jan, PhD, a professor of physiology, biochemistry and biophysics and a Howard Hughes Medical Institute investigator at UCSF. Jan led the study with his wife Lily Jan, PhD, who is also a UCSF professor and a Howard Hughes Medical Institute investigator.
The work sheds light on a poorly understood yet fundamental sense through which humans experience the world and derive pleasure and comfort.
Why is Touch Still Such a Mystery?
Scientists generally feel that, like those other senses, the sense of touch is governed by peripheral nerve fibers stretching from the spine to nerve endings all over the body. Special molecules in these nerve endings detect the mechanical movement of the skin surrounding them when it is touched, and they respond by opening and allowing ions to rush in. The nerve cell registers this response, and if the signal is strong enough, it will fire, signaling the gentle touch to the brain.
What has been missing from the picture, however, are the details of this process. The new finding is a milestone in that it defines the exact nerves and uncovers the identity of the NOMPC channel, one of the major molecular players involved—at least in flies.
Jan and his colleagues made this discovery through an unusual route. They were looking at the basic physiology of the developing fruit fly, examining how class III neurons develop in larvae. They noticed that when these cells developed in the insects, their nerve endings would always become branches into spiky “dendrites.”
Wanting to know what these neurons are responsible for, they examined them closely and found the protein NOMPC was abundant at the spiky ends. They then examined a fly genetically engineered to have a non-functioning form of NOMPC and showed that it was insensitive to gentle touch. They also showed that they could induce touch sensitivity in neurons that do not normally respond to gentle touch by inserting copies of the NOMPC protein into them.
(Image: Dietrich Meyer)