Why are elderly duped?

Why are elderly duped? Area in brain where doubt arises changes with age

ScienceDaily (Aug. 16, 2012) — Everyone knows the adage: "If something sounds too good to be true, then it probably is." Why, then, do some people fall for scams and why are older folks especially prone to being duped?

An answer, it seems, is because a specific area of the brain has deteriorated or is damaged, according to researchers at the University of Iowa. By examining patients with various forms of brain damage, the researchers report they've pinpointed the precise location in the human brain, called the ventromedial prefrontal cortex, that controls belief and doubt, and which explains why some of us are more gullible than others.

"The current study provides the first direct evidence beyond anecdotal reports that damage to the vmPFC (ventromedial prefrontal cortex) increases credulity. Indeed, this specific deficit may explain why highly intelligent vmPFC patients can fall victim to seemingly obvious fraud schemes," the researchers wrote in the paper published in a special issue of the journalFrontiers in Neuroscience.

A study conducted for the National Institute of Justice in 2009 concluded that nearly 12 percent of Americans 60 and older had been exploited financially by a family member or a stranger. And, a report last year by insurer MetLife Inc. estimated the annual loss by victims of elder financial abuse at $2.9 billion.

The authors point out their research can explain why the elderly are vulnerable.

"In our theory, the more effortful process of disbelief (to items initially believed) is mediated by the vmPFC, which, in old age, tends to disproportionately lose structural integrity and associated functionality," they wrote. "Thus, we suggest that vulnerability to misleading information, outright deception and fraud in older adults is the specific result of a deficit in the doubt process that is mediated by the vmPFC."

The ventromedial prefrontal cortex is an oval-shaped lobe about the size of a softball lodged in the front of the human head, right above the eyes. It's part of a larger area known to scientists since the extraordinary case of Phineas Gage that controls a range of emotions and behaviors, from impulsivity to poor planning. But brain scientists have struggled to identify which regions of the prefrontal cortex govern specific emotions and behaviors, including the cognitive seesaw between belief and doubt.

The UI team drew from its Neurological Patient Registry, which was established in 1982 and has more than 500 active members with various forms of damage to one or more regions in the brain. From that pool, the researchers chose 18 patients with damage to the ventromedial prefrontal cortex and 21 patients with damage outside the prefrontal cortex. Those patients, along with people with no brain damage, were shown advertisements mimicking ones flagged as misleading by the Federal Trade Commission to test how much they believed or doubted the ads. The deception in the ads was subtle; for example, an ad for "Legacy Luggage" that trumpets the gear as "American Quality" turned on the consumer's ability to distinguish whether the luggage was manufactured in the United States versus inspected in the country.

Each participant was asked to gauge how much he or she believed the deceptive ad and how likely he or she would buy the item if it were available. The researchers found that the patients with damage to the ventromedial prefrontal cortex were roughly twice as likely to believe a given ad, even when given disclaimer information pointing out it was misleading. And, they were more likely to buy the item, regardless of whether misleading information had been corrected.

"Behaviorally, they fail the test to the greatest extent," says Natalie Denburg, assistant professor in neurology who devised the ad tests. "They believe the ads the most, and they demonstrate the highest purchase intention. Taken together, it makes them the most vulnerable to being deceived." She added the sample size is small and further studies are warranted.

Apart from being damaged, the ventromedial prefrontal cortex begins to deteriorate as people reach age 60 and older, although the onset and the pace of deterioration varies, says Daniel Tranel, neurology and psychology professor at the UI and corresponding author on the paper. He thinks the finding will enable doctors, caregivers, and relatives to be more understanding of decision making by the elderly.

"And maybe protective," Tranel adds. "Instead of saying, 'How would you do something silly and transparently stupid,' people may have a better appreciation of the fact that older people have lost the biological mechanism that allows them to see the disadvantageous nature of their decisions."

The finding corroborates an idea studied by the paper's first author, Erik Asp, who wondered why damage to the prefrontal cortex would impair the ability to doubt but not the initial belief as well. Asp created a model, which he called the False Tagging Theory, to separate the two notions and confirm that doubt is housed in the prefrontal cortex.

"This study is strong empirical evidence suggesting that the False Tagging Theory is correct," says Asp, who earned his doctorate in neuroscience from the UI in May and is now at the University of Chicago.

Kenneth Manzel, Bryan Koestner, and Catherine Cole from the UI are contributing authors on the paper. The National Institute on Aging and the National Institute of Neurological Disorders and Stroke funded the research.

Journal Reference:

1. Erik Asp, Kenneth Manzel, Bryan Koestner, Catherine A. Cole, Natalie L. Denburg, Daniel Tranel. A Neuropsychological Test of Belief and Doubt: Damage to Ventromedial Prefrontal Cortex Increases Credulity for Misleading Advertising. Frontiers in Neuroscience, 2012; 6 DOI: 10.3389/fnins.2012.00100

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A GPS in your DNA

ScienceDaily (Aug. 16, 2012) — While your DNA is unique, it also tells the tale of your family line. It carries the genetic history of your ancestors down through the generations. Now, says a Tel Aviv University researcher, it's also possible to use it as a map to your family's past.

Prof. Eran Halperin of TAU's Blavatnik School of Computer Science and Department of Molecular Microbiology and Biotechnology, along with a group of researchers from University of California, Los Angeles, are giving new meaning to the term "genetic mapping." Using a probabilistic model of genetic traits for every coordinate on the globe, the researchers have developed a method for determining more precisely the geographical location of a person's ancestral origins.

The new method is able to pinpoint more specific locations for an individual's ancestors, for example placing an individual's father in Paris and mother in Barcelona. Previous methods would "split the difference" and place this origin inaccurately at a site between those two cities, such as Lyon.

Published in the journal Nature Genetics, this method has the potential to reveal the ancestry, origins, and migration patterns of many different human and animal populations. It could also be a new model for learning about the genome.

Points of origin

There are points in the human genome called SNPs that are manifested differently in each individual, explains Prof. Halperin. These points mutated sometime in the past and the mutation was then passed to a large part of the population in a particular geographic region. The probability of a person possessing these mutations today varies depending on the geographical location of those early ancestors.

"We wanted to ask, for example, about the probability of having the genetic mutation 'A' in a particular position on the genome based on geographical coordinates," he says. When you look at many of these positions together in a bigger picture, it's possible to group populations with the same mutation by point of origin.

To test their method, Prof. Halperin and his fellow researchers studied DNA samples from 1,157 people from across Europe. Using a probabilistic mathematical algorithm based on mutations in the genome, they were able to accurately determine their ancestral point or points of origin using only DNA data and the new mathematical model, unravelling genetic information to ascertain two separate points on the map for the mother and father. The researchers hope to extend this model to identify the origins of grandparents, great-grandparents, and so on.

The new method could provide information that has applications in population genetic studies -- to study a disease that impacts a particular group, for example. Researchers can track changes in different genomic traits across a map, such as the tendency for southern Europeans to have a mutation in a gene that causes lactose intolerance, a mutation missing from that gene in northern Europeans.

A closer look at migration

The researchers believe that their model could have also relevance for the animal kingdom, tracking the movement of animal populations. "In principle, you could figure out where the animals have migrated from, and as a result learn about habitat changes due to historical climate change or other factors," says Prof. Halperin.

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B Cell Survival Holds Key to Chronic Graft Vs. Host Disease

B cell survival holds key to chronic graft vs. host disease

ScienceDaily (Aug. 16, 2012) — A team from UNC Lineberger Comprehensive Cancer Center, shows in the laboratory that B cells from patients with chronic GVHD are much more active than cells from patients without the disease.

In chronic Graft vs. Host Disease (GVHD), the differences between the donor bone marrow cells and the recipient's body often cause these immune cells to recognize the recipient's body tissues as foreign and the newly transplanted cells attack the transplant recipient's body. Symptoms can range from dry eyes and dry mouth, hair loss and skin rashes, vulnerability to infection, liver and lung and digestive tract disorders. For patients who received bone marrow or stem cells, it is estimated that 40-70 percent may experience chronic GVHD.

B cells, which produce proteins called antibodies, are one type of immune cell involved in GVHD. In a paper published online August 15 by the journal, Blood, a team from the University of North Carolina's Lineberger Comprehensive Cancer Center, shows in the laboratory that B cells from patients with chronic GVHD are much more active than cells from patients without the disease. The team also outlines the cell signaling pathways that contribute to this increased activity -- identifying a promising target for developing new therapies for the diseases.

Jessica Allen, PhD, the paper's first author, says "We found that B cells from patients with active chronic GVHD were in a heightened metabolic state and resist programmed cell death."

Senior author, Stefanie Sarantopoulos, MD, PhD, assistant professor in the division of hematology/oncology and the departments of microbiology and immunology at the UNC School of Medicine, adds, "Steroids are currently our only standard treatment for chonic GVHD and they are often not effective. This study adds to our previously published work because it implicates the TNF family member protein called BAFF in the 'revved up' B-cell signaling we found in our patients. We hope to develop targeted therapeutic agents, like anti-BAFF agents or small molecule inhibitors of serine/ threonine kinases, for treatment of our chronic GVHD patients."

[Other UNC Lineberger researchers on the team include Albert Baldwin, PhD, Jonathan Serody, MD, Kristy Richards, MD, PhD, Thomas C. Shea, MD, Don A. Gabriel, MD, PhD, James Coghill, MD, Paul Armistead, MD, PhD, Matthew Fore, BA, and Jenna Wooten, PhD.

Additional team members from the UNC Stem Cell Transplant team and UNC Lineberger include Philip Roehrs, MD, Amber Essenmacher, Robert Irons, Allison Deal, Andrew Sharf, and Todd Hoffert.

Jerome Ritz MD, Corey Cutler, MD MPH, and Nazmim S. Bhuiya, BA, MPH from the Dana-Farber Cancer Institute also contributed to the research.

The study could not have been performed without the gracious consent of transplant patients at UNC and Dana Farber who donated extra blood samples. The University Cancer Research Fund (UCRF) and the UNC Tissue Procurement Core Facility supported collection of de-identified patient samples for these laboratory studies.

The research was funded by the National Marrow Donor Program through the Be The Match Foundation and National Institutes of Health grants K08HL107756 and CA142106.

Leukemia and lymphoma patients who receive life-saving stem cell or bone marrow transplants often experience chronic side effects that significantly decrease quality of life, can last a lifetime, and ultimately affect their long-term survival.]

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molecular trigger for wound-healing

Scientists find an important molecular trigger for wound-healing

ScienceDaily (Aug. 16, 2012) — Scientists at The Scripps Research Institute have made a breakthrough in understanding a class of cells that help wounds in skin and other epithelial tissues heal, uncovering a molecular mechanism that pushes the body into wound-repair mode.

The findings, which appear in an advance, online version of the Immunity on August 16, 2012, focus on cells known as γδ (gamma delta) T cells. The new study demonstrates a skin-cell receptor hooks up with a receptor on γδ T-cells to stimulate wound healing.

"This is a major activation pathway for γδ T cells, and it may be a key to treating slow-wound-healing conditions, such as we see in diabetes," said Scripps Research Professor Wendy L. Havran, senior author of the study. "Chronic non-healing wounds among diabetics and the elderly are an increasing clinical problem."

Rounding and Multiplying

Havran's laboratory specializes in the study of γδ T cells, and the team has produced many of the findings in this research field, including the discovery of these cells' major role in epithelial wound repair. Epithelial tissues are barrier tissues to the outside world, such as skin and the inner surfaces of the gut and lungs.

Normally, γδ T cells reside in these tissues and extend finger-like projections, called dendrites, that contact neighboring epithelial cells. When injury or infection occurs, the epithelial cells signal their damaged condition to the γδ T cells. In response, the T cells retract their dendrites, become round, start proliferating, and secrete growth-factor proteins that stimulate the production of new epithelial cells in the vicinity -- thus helping to repair the wound.

Researchers know of very few interactions between epithelial cells and γδ T cells that are involved in this process. Two, however, are known to be crucial. One of these is through the gd T cell receptor and the other was described in a 2010 Science paper, whose first author was Havran laboratory Senior Staff Scientist Deborah A. Witherden. But these two interactions don't fully explain the transformation that γδ T cells undergo in the vicinity of wounds. "We've wanted to learn more about the molecules that mediate this dramatic change," Havran said.

Signaling a Transformation

To do that, Witherden identified an antibody that could block keratinocytes' ability to activate γδ T cells in culture. She found that the antibody bound to a keratinocyte surface receptor called plexin B2. She also found that when lab mice have small skin wounds, their injured keratinocytes express more plexin B2 soon after the wounding occurs -- pointing to a role for plexin B2 in signaling skin-cell damage.

The next step was to find plexin B2's signaling partner on γδ T cells. "Plexin B2 is very similar to other plexin B family members, including plexin B1, which previously has been shown to bind the CD100 receptor on T cells," said Witherden. "So we thought that perhaps plexin B2 and CD100 can interact as well."

Further tests revealed that plexin B2 and CD100 do indeed bind tightly together; moreover, γδ T cells can't go fully into wound-repair mode when they lack CD100. Witherden found as well that skin wounds in mice take an extra day or two to heal when the mice don't have this receptor. "This is very similar to what we see in mice that lack γδ T cells altogether," she said.

Removing CD100 from other types of T cells had no effect on wound healing time, indicating that the absence of this receptor specifically on γδ T cells is the reason for the slower healing.

By stimulating CD100 with plexin B2 molecules or even with CD100-binding antibodies, the team showed that this receptor is the principal trigger for the dramatic appendage-retraction and rounding phenomenon seen in γδ T cells after nearby wounds. Without it, the T cells are largely unable to undergo this transformation. "This rounding process seems to be vital for these T cells to function normally in wound healing," said Witherden.

Potential Clinical Significance

In early follow-on work, the team has found evidence that this same plexin B2-CD100 interaction is also needed for the prompt activation of γδ T cells and wound healing in the lining of mouse intestines -- which suggests that this receptor helps govern wound healing in epithelial tissues generally.

The finding clearly is important for the basic scientific understanding of T cells and their functions. But it is likely to have medical significance, too. Non-healing wounds affect more than 4 million people in the United States and are the leading cause of amputations. These chronic wounds have a major impact on patient's lives and result in enormous health care costs. "If deficiencies in this γδ T cell activation pathway are even partly responsible, then we may be able to develop drugs to boost this pathway and treat conditions involving chronic non-healing wounds," said Havran.

The γδ T cell population appears to be involved not just in wound healing, but also in defending against other threats to epithelial tissues. "One of the future directions of our research will be to understand the roles of these molecules in gd T cell activation pathways in fighting infections and tumors," she added.

Journal Reference:

1. Deborah A. Witherden, Megumi Watanabe, Olivia Garijo, Stephanie E. Rieder, Gor Sarkisyan, Shane J.F. Cronin, Petra Verdino, Ian A. Wilson, Atsushi Kumanogoh, Hitoshi Kikutani, Luc Teyton, Wolfgang H. Fischer, Wendy L. Havran. The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function.Immunity, 2012; DOI: 10.1016/j.immuni.2012.05.026

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increase in size of the human brain explained

Evolutionary increase in size of the human brain explained: Part of a protein linked to rapid change in cognitive ability

ScienceDaily (Aug. 16, 2012) — Researchers have found what they believe is the key to understanding why the human brain is larger and more complex than that of other animals.

The human brain, with its unequaled cognitive capacity, evolved rapidly and dramatically.

"We wanted to know why," says James Sikela, PhD, who headed the international research team that included researchers from the University of Colorado School of Medicine, Baylor College of Medicine and the National Institutes of Mental Health. "The size and cognitive capacity of the human brain sets us apart. But how did that happen?"

"This research indicates that what drove the evolutionary expansion of the human brain may well be a specific unit within a protein -- called a protein domain -- that is far more numerous in humans than other species."

The protein domain at issue is DUF1220. Humans have more than 270 copies of DUF1220 encoded in the genome, far more than other species. The closer a species is to humans, the more copies of DUF1220 show up. Chimpanzees have the next highest number, 125. Gorillas have 99, marmosets 30 and mice just one. "The one over-riding theme that we saw repeatedly was that the more copies of DUF1220 in the genome, the bigger the brain. And this held true whether we looked at different species or within the human population."

Sikela, a professor at the CU medical school, and his team also linked DUF1220 to brain disorders. They associated lower numbers of DUF1220 with microcephaly, when the brain is too small; larger numbers of the protein domain were associated with macrocephaly, when the brain is too large.

The findings were reported today in the online edition of The American Journal of Human Genetics. The researchers drew their conclusions by comparing genome sequences from humans and other animals as well as by looking at the DNA of individuals with microcephaly and macrocephaly and of people from a non-disease population.

"The take home message was that brain size may be to a large degree a matter of protein domain dosage," Sikela says. "This discovery opens many new doors. It provides new tools to diagnose diseases related to brain size. And more broadly, it points to a new way to study the human brain and its dramatic increase in size and ability over what, in evolutionary terms, is a short amount of time."

Journal Reference:

1. Laura J. Dumas, Majesta S. O’Bleness, Jonathan M. Davis, C. Michael Dickens, Nathan Anderson, J.G. Keeney, Jay Jackson, Megan Sikela, Armin Raznahan, Jay Giedd, Judith Rapoport, Sandesh S.C. Nagamani, Ayelet Erez, Nicola Brunetti-Pierri, Rachel Sugalski, James R. Lupski, Tasha Fingerlin, Sau Wai Cheung, James M. Sikela. DUF1220-Domain Copy Number Implicated in Human Brain-Size Pathology and Evolution. The American Journal of Human Genetics, 2012; DOI: 10.1016/j.ajhg.2012.07.016

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