Posts tagged science
Articles and news from the latest research reports.
Researchers map the expression patterns of 1,000 genes in the human brain.
The paper
H. Zeng et al., “Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures,” Cell, 149:48-96, 2012.
The finding
Whole-genome sequencing has given researchers a good sense of which genes are shared between, for example, humans and mice. But little is known about how the expression patterns of these genes differ. Hongkui Zeng of the Allen Institute for Brain Science in Seattle, Washington, and colleagues took slices of human brains collected from postmortem biopsies and tested the expression of 1,000 key neuronal genes. They found that about 21 percent of the gene-expression profiles differed between the two species.
The sliver
Researchers took thin slices from regions of the brain involved in processing visual and sensory information and scanned them for the in situ expression of 1,000 genes that act as markers of cell type or are involved in disease, evolution, or cortical function. They compared gene expression of three areas of the cortex across 46 donors with corresponding mouse-brain slices, which had been analyzed previously at the Allen Institute.
The difference
The differences between humans and mice “often manifested in a cell type-specific way,” said Zeng, or involved in between-cell communications. “The disease genes are all very well conserved,” which bodes well for researchers using mice as models of disease, she says.
The impact
“The mouse model is used extensively in neuroscience research, and it’s assumed to be a surrogate for the human,” says Daniel Geschwind, a neurogeneticist at the University of California, Los Angeles. Knowing the specific differences “gives you a sense that many things are conserved, but also provides some guidance as to the ones that aren’t.”
Sick from Stress? Blame Your Mom… And Epigenetics
If you’re sick from stress, a new research report appearing in the August 2012 issue of The FASEB Journal suggests that what your mother ate — or didn’t eat — may be part of the cause. The report shows that choline intake that is higher than what is generally recommended during pregnancy may improve how a child responds to stress. These improvements are the result of epigenetic changes that ultimately lead to lower cortisol levels. Epigenetic changes affect how a gene functions, even if the gene itself is not changed. Lowering cortisol is important as high levels of cortisol are linked to a wide range of problems ranging from mental health to metabolic and cardiovascular disorders.
Protein Involved in DNA Replication, Centrosome Regulation Linked to Dwarfism, Small Brain Size
ScienceDaily (July 31, 2012) — Research just published by scientists at Cold Spring Harbor Laboratory (CSHL) links gene mutations found in some patients with Meier-Gorlin syndrome (MGS) with specific cellular dysfunctions that are thought to give rise to a particularly extreme version of dwarfism, small brain size, and other manifestations of abnormal growth which generally characterize that rare condition.
Although only 53 cases of Meier-Gorlin syndrome have been reported in the medical literature since the first patient was described in 1959, it is a malady whose mechanisms are bringing to light new functions for some of the cellular processes common to all life. Pathology related to MGS is traced in the new research to one of these, the fundamental process called mitosis in which cells replicate their genetic material and prepare to divide into two identical “daughter” cells.
CSHL President and Professor Bruce Stillman, Ph.D., a cancer biologist who has made seminal discoveries over three decades that have helped reveal the exquisite choreography of how chromosomes are duplicated in cells, led the new research, which suggests how, during mitosis, mutant versions of a protein called Orc1 contribute in two distinct ways to severe MGS pathology. The research is published online ahead of print in Genes & Development.
Most creatures need a good sense of balance — especially tree-dwellers that swing among high branches. In mammals, the ability largely comes from three loop-shaped structures in the inner ear called semicircular canals; in most species, the size, shape, and arrangement of those loops (inset) is extremely consistent from one individual to another. But in three-toed sloths (such as Bradypus variegatus, the brown-throated three-toed sloth, pictured), many proportions of the semicircular canals are surprisingly variable from one sloth to another.
The overall variability is at least twice that seen in other species of mammals the team analyzed, researchers report online today in the Proceedings of the Royal Society B. That high degree of variation stems from the sloths’ languid lifestyle, the researchers suggest.
Sloths, which move extremely slowly when they move at all, don’t require the sense of balance that a swift, agile creature such as a primate needs. The finding supports one of Charles Darwin’s notions about evolution: If an organ isn’t crucial, variations in its structure or performance aren’t lost over time, keeping the potpourri in the population.
Artificial Beginnings: Understanding the Origin of Life by Recreating It
The Origin of Life on Earth was certainly, in retrospect, and from the human vantage point, the most fateful event in the history of the Universe. On a young, tepid Earth chemistry sprung into biology and set course on a four billion year journey that would eventually lead to us. However, all traces of the first, primitive organisms have vanished. They were outcompeted and devoured by their evolutionary descendents, leaving nothing to form fossils. Though we will never be able to set eyes on the first Earthlings, the first pioneers, we can understand what they must have been like through more subtle, indirect approaches. Comparative biochemistry across the whole of life takes us back quite a ways, though not to the first cells. The most recent common ancestor shared by all living organisms—bacteria, plants, animals, fungi, archaea, and unicellular eukaryotes like amoebae—was born long after the first cell ceased to exist. The only way we can truly understand what life must have been like in its earliest days is to create it ourselves.
Opioid Receptors as a Drug Target for Stopping Obesity
ScienceDaily (July 31, 2012) — New research demonstrates that blocking the delta opioid receptor in mice created resistance to weight gain and stimulated gene expression promoting non-shivering thermogenesis.
Imagine eating all of the sugar and fat that you want without gaining a pound. Thanks to new research published in The FASEB Journal, the day may come when this is not too far from reality. That’s because researchers from the United States and Europe have found that blocking one of three opioid receptors in your body could turn your penchant for sweets and fried treats into a weight loss strategy that actually works. By blocking the delta opioid receptor, or DOR, mice reduced their body weight despite being fed a diet high in fat and sugar. The scientists believe that the deletion of the DOR gene in mice stimulated the expression of other genes in brown adipose tissue that promoted thermogenesis.
"Our study provided further evidence that opioid receptors can control the metabolic response to diets high in fat and sugar, and raise the possibility that these gene products (or their respective pathways) can be targeted specifically to treat excess weight and obesity," said Traci A. Czyzyk, Ph.D., a researcher involved in the work from the Department of Physiology at the Mayo Clinic in Scottsdale, Arizona.
Scientists studied mice lacking the delta opioid receptor (DOR KO) and wild type (WT) control mice who were fed an energy dense diet (HED), high in fat and sugar, for three months. They found that DOR KO mice had a lean phenotype specifically when they were fed the HED. While WT mice gained significant weight and fat mass on this diet, DOR KO mice remained lean even though they consumed more food. Researchers then sought to determine how DOR might regulate energy balance and found that DOR KO mice were able to maintain their energy expenditure levels, in part, due to an increase in non-shivering thermogenesis. This was evidenced by an increase in thermogenesis-promoting genes in brown adipose tissue, an increase in body surface temperature near major brown adipose tissue depots, and the ability of DOR KO mice to maintain higher core body temperatures in response to being in a cold environment.
"Don’t reach for the ice cream and doughnuts just yet," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “We don’t know how all this works in humans, and of course, a diet of junk food causes other health problems. This exciting research identifies genes that activate brown adipose tissue to increase our burning of calories from any source. It may lead to a safe diet pill in the future.”
Source: Science Daily
Research team finds possible clue to progression of multiple sclerosis
July 31, 2012
Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.
B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.
In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.
The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.
The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons.
The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.
"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.
The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.
Provided by Wayne State University
Source: medicalxpress.com
Donepezil found helpful in dementia with lewy bodies
July 31, 2012
(HealthDay) — For patients with dementia with Lewy bodies (DLB), treatment with 5 or 10 mg/day donepezil is associated with significant cognitive, behavioral, and global function improvements, according to research published in the July issue of the Annals of Neurology.
Etsuro Mori, M.D., Ph.D., of the Tohoku University Graduate School of Medicine in Sendai, Japan, and colleagues conducted a randomized, double-blind, placebo-controlled trial involving 140 patients with DLB who received either placebo or 3, 5, or 10 mg of donepezil hydrochloride per day for 12 weeks (35, 35, 33, and 37 patients, respectively). Cognitive function was measured using the Mini-Mental State Examination (MMSE); behavioral changes were measured using the Neuropsychiatric Inventory; global function was evaluated using the Clinician’s Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus); and caregiver burden was also assessed.
The researchers found that, compared with placebo treatment, the MMSE scores were significantly better with donepezil 5 mg (mean difference, 3.8) and 10 mg (mean difference, 2.4), but the 3 mg/day dose was not significantly better than placebo (P = 0.017). Donepezil at doses of 3, 5, and 10 mg/day correlated with significant improvements versus placebo on CIBIC-plus. Both the 5 and 10 mg doses of donepezil resulted in significant improvements in behavioral measures. Caregiver burden also improved, but only with the 10 mg/day dose. The safety results were similar among the groups and were consistent with the known profile.
"Donepezil at 5 and 10 mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose," the authors write. Several authors disclosed financial ties to pharmaceutical companies, including Eisai Co., which funded the study and manufactures donepezil.
Source: medicalxpress.com
When We Forget to Remember: Failures in Prospective Memory Range from Annoying to Lethal
A surgical team closes an abdominal incision, successfully completing a difficult operation. Weeks later, the patient comes into the ER complaining of abdominal pain and an X-ray reveals that one of the forceps used in the operation was left inside the patient. Why would highly skilled professionals forget to perform a simple task they have executed without difficulty thousands of times before?
These kinds of oversights occur in professions as diverse as aviation and computer programming, but research from psychological science reveals that these lapses may not reflect carelessness or lack of skill but failures of prospective memory.
Failures of prospective memory typically occur when we form an intention to do something later, become engaged with various other tasks, and lose focus on the thing we originally intended to do. Despite the name, prospective memory actually depends on several cognitive processes, including planning, attention, and task management. Common in everyday life, these memory lapses are mostly annoying, but can have tragic consequences.
Concussions and head impacts may accelerate brain aging
Jul 31, 2012 by Laura Bailey
Concussions and even lesser head impacts may speed up the brain’s natural aging process by causing signaling pathways in the brain to break down more quickly than they would in someone who has never suffered a brain injury or concussion.
The photos compare images of two brains, one with and without head injury. The red areas indicates electrical activity in response to the task researchers asked study participants to perform, and non-injured brains show more red, thus more electrical activity during the task. Image courtesy of Steven Broglio
Researchers from the University of Michigan School of Kinesiology and the U-M Health System looked at college students with and without a history of concussion and found changes in gait, balance and in the brain’s electrical activity, specifically attention and impulse control, said Steven Broglio, assistant professor of kinesiology and director of the Neurotrauma Research Laboratory.
The declines were present in the brain injury group up to six years after injury, though the differences between the study groups were very subtle, and outwardly all of the participants looked and acted the same.
Broglio, who is also affiliated with Michigan NeuroSport, stressed that the studies lay out a hypothesis where concussions and head impacts accelerate the brain’s natural aging process.
The study, “Cognitive decline and aging: The role of concussive and subconcussive impacts,” appears in the July issue of journal Exercise and Sport Sciences Reviews.
"The last thing we want is for people to panic. Just because you’ve had a concussion does not mean your brain will age more quickly or you’ll get Alzheimer’s," Broglio said. "We are only proposing how being hit in the head may lead to these other conditions, but we don’t know how it all goes together just yet."
Broglio stressed that other factors, such as lifestyle choices, smoking, alcohol consumption, physical exercise, family history and whether or not you “exercise” your brain also impact the brain’s aging process. Concussion may only be one small factor.
To begin to understand how concussions might impact brain activity and its signaling pathways, researchers asked the participants to perform certain tasks in front of a computer, and took images of their brains. The brains of the nonconcussed group showed a greater area of electrical activation than the participants with a history of brain injury.
The signaling pathways in our brains are analogous to a five-lane highway. On a new highway, traffic runs smoothly and quickly as all lanes are in top shape. However, during normal aging, the asphalt deteriorates and lanes might become bumpy or even unusable. Traffic slows.
Similarly, our brains start with all pathways clear to transfer electrical signals rapidly. As we age, the brain’s pathways break down and can’t transfer the information as quickly. Concussive and other impacts to the head may result in a ‘pothole’ on the brain’s highway, causing varying degrees of damage and speeding the pathway’s natural deterioration.
"What we don’t know is if you had a single concussion in high school, does that mean you will get dementia at age 50?" Broglio said. "Clinically, we don’t see that. What we think is it will be a dose response.
"So, if you played soccer and sustained some head impacts and maybe one concussion, then you may have a little risk. If you went on and played in college and took more head balls and sustained two more concussions, you’re probably at a little bigger risk. Then if you play professionally for a few years, and take more hits to the head, you increase the risk even more. We believe it’s a cumulative effect."
In the next phase of study, researchers will look at people in their 20s, 40s and 60s who did and did not sustain concussions during high school sports. They hope to learn if there is an increasing effect of concussion as the study subjects age. If interested in participating in the study, email neurotraumalab.umich@gmail.com.
Researchers from the departments of Physical Medicine and Rehabilitation, and Neurology, and the Michigan Alzheimer’s Disease Center also participated in the study.
Source: University of Michigan