intellectual vanities… about close to everything

Archive for December 2007

Monkeys Outsmart College Studends At Mental Addition

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Researchers at Duke University have demonstrated that monkeys have the ability to perform mental addition. In fact, monkeys performed about as well as college students given the same test.
Two rhesus macaque monkeys. Nonhuman primate subjects were two adult female rhesus macaques, named Feinstein and Boxer. (Credit: iStockphoto/Claire George)

The findings shed light on the shared evolutionary origins of arithmetic ability in humans and non-human animals, according to Assistant Professor Elizabeth Brannon, Ph.D. and Jessica Cantlon, Ph.D., of the Duke Center for Cognitive Neuroscience.

Current evidence has shown that both humans and animals have the ability to mentally represent and compare numbers. For instance, animals, infants and adults can discriminate between four objects and eight objects. However, until now it was unclear whether animals could perform mental arithmetic.

“We know that animals can recognize quantities, but there is less evidence for their ability to carry out explicit mathematical tasks, such as addition,” said graduate student Jessica Cantlon. “Our study shows that they can.”

Cantlon and Brannon set up an experiment in which macaque monkeys were placed in front of a computer touch screen displaying a variable number of dots. Those dots were then removed and a new screen appeared with a different number of dots. A third screen then appeared displaying two boxes; one containing the sum of the first two sets of dots and one containing a different number. The monkeys were rewarded for touching the box containing the correct sum of the sets.

The same test was presented to college students, who were asked to choose the correct sum without counting the individual dots. While the college students were correct 94 percent the time and the monkeys 76 percent, the average response time for both monkeys and humans was about one second.

Interestingly, both the monkeys’ and the college students’ performance worsened when the two choice boxes were close in number.

“If the correct sum was 11 and the box with the incorrect number held 12 dots, both monkeys and the college students took longer to answer and had more errors. We call this the ratio effect,” explained Cantlon. “What’s remarkable is that both species suffered from the ratio effect at virtually the same rate.”

That monkeys and humans share the ability to add suggests that basic arithmetic may be part of our shared evolutionary past.

Humans have added language and writing to their repertoire, which undoubtedly changes the way we represent numbers. “Much of adult humans’ mathematical capacity lies in their ability to represent numerical concepts using symbolic language. A monkey can’t tell the difference between 2000 and 2001 objects, for instance. However, our work has shown that both humans and monkeys can mentally manipulate representations of number to generate approximate sums of individual objects,” says Brannon.

Cantlon JF, Brannon EM (2007) Basic Math in Monkeys and College Students. PLoS Biol 5(12): e328 doi:10.1371/journal.pbio.0050328

 Adult humans possess a sophisticated repertoire of mathematical faculties. Many of these capacities are rooted in symbolic language and are therefore unlikely to be shared with nonhuman animals. However, a subset of these skills is shared with other animals, and this set is considered a cognitive vestige of our common evolutionary history. Current evidence indicates that humans and nonhuman animals share a core set of abilities for representing and comparing approximate numerosities nonverbally; however, it remains unclear whether nonhuman animals can perform approximate mental arithmetic. Here we show that monkeys can mentally add the numerical values of two sets of objects and choose a visual array that roughly corresponds to the arithmetic sum of these two sets. Furthermore, monkeys’ performance during these calculations adheres to the same pattern as humans tested on the same nonverbal addition task. Our data demonstrate that nonverbal arithmetic is not unique to humans but is instead part of an evolutionarily primitive system for mathematical thinking shared by monkeys.

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Written by huehueteotl

December 21, 2007 at 11:42 am

Moments Of Horror That Will Not Pass?

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In The Matrix, hero Neo wins his battles when time slows in the simulated world. In the real world, accident victims often report a similar slowing as they slide unavoidably into disaster. But can humans really experience events in slow motion?

Dr. David Eagleman adjusts the perceptual chronometer during Suspended Catch Air Device diving experiments. (Credit: Image courtesy of Baylor College of Medicine)

Apparently not, said researchers at Baylor College of Medicine in Houston, who studied how volunteers experience time when they free-fall 100 feet into a net below. Even though participants remembered their own falls as having taken one-third longer than those of the other study participants, they were not able to see more events in time. Instead, the longer duration was a trick of their memory, not an actual slow-motion experience.
“People commonly report that time seemed to move in slow motion during a car accident,” said Dr. David Eagleman, assistant professor of neuroscience and psychiatry and behavioral sciences at BCM. “Does the experience of slow motion really happen, or does it only seem to have happened in retrospect? The answer is critical for understanding how time is represented in the brain.”

When roller coasters and other scary amusement park rides did not cause enough fear to make “time slow down,” Eagleman and his graduate students Chess Stetson and Matthew Fiesta sought out something even more frightening. They hit upon Suspended Catch Air Device diving, a controlled free-fall system in which “divers” are dropped backwards off a platform 150 feet up and land safely in a net. Divers are not attached to ropes and reach 70 miles per hour during the three-second fall.

“It’s the scariest thing I have ever done,” said Eagleman. “I knew it was perfectly safe, and I also knew that it would be the perfect way to make people feel as though an event took much longer than it actually did.”

The experiment consisted of two parts. In one, the researchers asked participants to reproduce with a stopwatch how long it took someone else to fall, and then how long their own fall seemed to have lasted. In general, people estimated that their own fall appeared 36 percent longer than that of their compatriots.

However, to determine whether that distortion meant they could actually see more events happening in time — like a camera in slow motion — Eagleman and his students developed a special device called the perceptual chronometer that was strapped to the volunteers’ wrists. Numbers flickered on the screen of the watch-like unit. The scientists adjusted the speed at which the numbers flickered until it was too fast for the divers to see.

They theorized that if time perception really slowed, the flickering numbers would appear slow enough for the divers to easily read while in free-fall.

They found that while the subjects were able to read numbers presented at normal speeds during the free-fall, they could not read them at faster-than-normal speeds.

“We discovered that people are not like Neo in The Matrix, dodging bullets in slow-mo. The paradox is that it seemed to participants as though their fall took a long time. The answer to the paradox is that time estimation and memory are intertwined: the volunteers merely thought the fall took a longer time in retrospect,” he said.

During a frightening event, a brain area called the amygdala becomes more active, laying down a secondary set of memories that go along with those normally taken care of by other parts of the brain.

“In this way, frightening events are associated with richer and denser memories. And the more memory you have of an event, the longer you believe it took,” Eagleman explained.

The study allowed them to deduce that a person’s perception of time is not a single phenomenon that speeds or slows. “Your brain is not like a video camera,” said Eagleman.

Eagleman and his team have been able to verify this conclusion in the laboratory. In an experiment that appeared in a recent issue of PLoS One, Eagleman and graduate student Vani Pariyadath used ‘oddballs’ in a sequence to bring about a similar duration distortion. For example, when they flashed on the computer screen a shoe, a shoe, a shoe, a flower and a shoe, viewers believed the flower stayed on the screen longer, even though it remained there the same amount of time as the shoes.

Pariyadath and Eagleman showed that even though durations are distorted during the oddball, other aspects of time — such as flickering lights or accompanying sounds — do not change.

The conclusion from both studies was the same.

“It can seem as though an event has taken an unusually long time, but it doesn’t mean your immediate experience of time actually expands. It simply means that when you look back on it, you believe it to have taken longer,” Eagleman said.

“This is related to the phenomenon that time seems to speed up as you grow older. When you’re a child, you lay down rich memories for all your experiences; when your older, you’ve seen it all before and lay down fewer memories. Therefore, when a child looks back at the end of a summer, it seems to have lasted forever; adults think it zoomed by.”

PLoS ONE. 2007 Nov 28;2(11):e1264.
The effect of predictability on subjective duration.

Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America.

Events can sometimes appear longer or shorter in duration than other events of equal length. For example, in a repeated presentation of auditory or visual stimuli, an unexpected object of equivalent duration appears to last longer. Illusions of duration distortion beg an important question of time representation: when durations dilate or contract, does time in general slow down or speed up during that moment? In other words, what entailments do duration distortions have with respect to other timing judgments? We here show that when a sound or visual flicker is presented in conjunction with an unexpected visual stimulus, neither the pitch of the sound nor the frequency of the flicker is affected by the apparent duration dilation. This demonstrates that subjective time in general is not slowed; instead, duration judgments can be manipulated with no concurrent impact on other temporal judgments. Like spatial vision, time perception appears to be underpinned by a collaboration of separate neural mechanisms that usually work in concert but are separable. We further show that the duration dilation of an unexpected stimulus is not enhanced by increasing its saliency, suggesting that the effect is more closely related to prediction violation than enhanced attention. Finally, duration distortions induced by violations of progressive number sequences implicate the involvement of high-level predictability, suggesting the involvement of areas higher than primary visual cortex. We suggest that duration distortions can be understood in terms of repetition suppression, in which neural responses to repeated stimuli are diminished.

Traffic Jam Mystery Solved

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Mathematicians from the University of Exeter have solved the mystery of traffic jams by developing a model to show how major delays occur on our roads, with no apparent cause. Many traffic jams leave drivers baffled as they finally reach the end of a tail-back to find no visible cause for their delay. Now, a team of mathematicians from the Universities of Exeter, Bristol and Budapest, have found the answer and published their findings in the journal Proceedings of the Royal Society.

iStockphoto/Tim McCaig

The team developed a mathematical model to show the impact of unexpected events such as a lorry (tractor trailer) pulling out of its lane on a dual carriageway (divided highway with median between traffic going in opposite directions). Their model revealed that slowing down below a critical speed when reacting to such an event, a driver would force the car behind to slow down further and the next car back to reduce its speed further still. The result of this is that several miles back, cars would finally grind to a halt, with drivers oblivious to the reason for their delay.

The model predicts that this is a very typical scenario on a busy highway (above 15 vehicles per km). The jam moves backwards through the traffic creating a so-called ‘backward travelling wave’, which drivers may encounter many miles upstream, several minutes after it was triggered.

Dr Gábor Orosz of the University of Exeter said: “As many of us prepare to travel long distances to see family and friends over Christmas, we’re likely to experience the frustration of getting stuck in a traffic jam that seems to have no cause. Our model shows that overreaction of a single driver can have enormous impact on the rest of the traffic, leading to massive delays.”

Drivers and policy-makers have not previously known why jams like this occur, though many have put it down to the sheer volume of traffic. While this clearly plays a part in this new theory, the main issue is around the smoothness of traffic flow. According to the model, heavy traffic will not automatically lead to congestion but can be smooth-flowing. This model takes into account the time-delay in drivers’ reactions, which lead to drivers braking more heavily than would have been necessary had they identified and reacted to a problem ahead a second earlier.

Dr Orosz continued: “When you tap your brake, the traffic may come to a full stand-still several miles behind you. It really matters how hard you brake – a slight braking from a driver who has identified a problem early will allow the traffic flow to remain smooth. Heavier braking, usually caused by a driver reacting late to a problem, can affect traffic flow for many miles.”

The research team now plans to develop a model for cars equipped with new electronic devices, which could cut down on over-braking as a result of slow reactions.

Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Volume 462, Number 2073 / September 08, 2006 2643-2670 DOI:10.1098/rspa.2006.1660

Subcritical Hopf bifurcations in a car-following model with reaction-time delay

Gábor Orosz1, Gábor Stépán2
1Bristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Queen’s Building, University Walk, Bristol BS8 1TR, UK
2Department of Applied Mechanics, Budapest University of Technology and Economics, PO Box 91, Budapest 1521, Hungary
A nonlinear car-following model of highway traffic is considered, which includes the reaction-time delay of drivers. Linear stability analysis shows that the uniform flow equilibrium of the system loses its stability via Hopf bifurcations and thus oscillations can appear. The stability and amplitudes of the oscillations are determined with the help of normal-form calculations of the Hopf bifurcation that also handles the essential translational symmetry of the system. We show that the subcritical case of the Hopf bifurcation occurs robustly, which indicates the possibility of bistability. We also show how these oscillations lead to spatial wave formation as can be observed in real-world traffic flows.

Sexing the Body: Gender Politics and the Construction of Sexuality. By Anne Fausto-Sterling.

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sexing_the_body.jpgNew York: Basic Books, 2000, 473 pages. Cloth, $35.00.

Sexing the Body: Gender Politics and the Construction of Sexuality. – Review – book review
Journal of Sex Research, Feb, 2001 by William B. Stanley

The prevailing theory of sexual dimorphism in Western culture can be traced to antiquity, in the work of philosophers like Aristotle and in the Judeo-Christian religious tradition. These early ideas have had a powerful influence on our views of sex and sexuality. Throughout most of our history, the policing of sex categories and related sexual behavior was largely left to religious and civil authorities. During the nineteenth century, however, the power to discipline sex and sexuality gradually shifted to the scientific and medical communities which took the lead in defining sex categories and what was normal with regard to sex, gender, and sexuality (Dreger, 1998; Herdt, 1996).
Among the most significant scientific influences on the reification of a theory of sexual dimorphism in the nineteenth century was the work of Charles Darwin. His evolutionary theory held that the sexual categories male and female emerged to serve the fundamental purpose of species reproduction required for natural selection and survival. The binary sex categories and the characteristics that distinguished them were defined as natural across time and place, a phylogenetically inherited structure of two basic types of human groups. By the end of the nineteenth century, male and female came to be seen as “innate structures in all forms of life … [and] heterosexuality as the teleologically necessary and highest form of sexual evolution” (Herdt, 1996, p. 28).

We outline this brief history to provide a context for the importance of Fausto-Sterling’s book Sexing the Body. This is a most provocative book containing a radical perspective. Fausto-Sterling considers problematic what she describes as our reliance on false dichotomies like nature/nurture, biology/culture, and essentialism/constructivism, and offers a persuasive argument for abandoning our current theories of sexual dimorphism. The persuasiveness of the book comes from its even-handedness and well-researched content (it took Fausto-Sterling more than 6 years to complete her research and writing).

The 225-page narrative portion of the book is clearly written and guides the reader through some very difficult issues and scholarship. Fausto-Sterling also makes creative use of artwork, illustrations, cartoons, and helpful charts and tables. In addition, the book contains 122 pages of footnotes, 67 pages of bibliography, and a detailed index.

Sexing the Body is divided into nine chapters that move from an analysis of the external markers for sex (e.g., anatomy, genitals), to an examination of the brain, sex glands, hormones, and genes as each has become part of the current discourse on sex. The book concludes with a chapter that describes an interdisciplinary, dynamic systems approach to the study of sex, gender, and sexuality.

Fausto-Sterling provides a fair and even-handed treatment of the issues and has taken the time to study the literature in a way that respects the scholarship of those with whom she has significant disagreements. For example, she is careful to explain the complexities of the psychosexual neutrality theory proposed by Money, Ehrhardt, and the Hampsons. She notes that Money’s ideas were never quite as simplistic as some of his critics (e.g., Milton Diamond) have charged.

In addition, Fausto-Sterling, a committed feminist, is not hesitant to criticize the limitations of certain feminist positions that are dualistic or essentialist. She is also open to the criticisms of her own work, crediting social psychologist Kessler for explaining the limitations of her earlier views on sexual categories as represented in the now famous 1993 article on “the five sexes.” And she admits that her earlier characterization of Young’s work in 1995 was not fully accurate, although she still maintains her basic critique of Young’s overemphasis on biological explanations for sexuality.

Fausto-Sterling brings an unusual interdisciplinary perspective to the study of sexuality. As a scientist and biologist, she believes in a material world and understands the importance of experimentation. However, her knowledge of feminist scholarship and the history of science has led her to focus on how the production of scientific knowledge is influenced by and rooted in particular histories, human practices, language, politics, and culture. In her view, scientific “facts” are not universal but always constructed within a particular historical and social context. As our social views have changed, so too have our scientific views of sexuality and the human body.

The influence of Foucault’s ideas on disciplines and regimes of truth is also evident in Sexing the Body. Foucault claimed that the structural constraints of the disciplines shape how we are able to look at the world. He also described how our concepts of normalcy emerge to become taken-for-granted knowledge. The influence of normalcy in the study of sexuality has been particularly pernicious. In chapters three and four, Fausto-Sterling presents an historical overview and analysis of how a medical discourse emerged to provide a scientific rationale for sex assignment and the surgical “correction” of an intersexed infant’s genitals. Given the impact of our theoretical assumptions regarding sexual dimorphism, it is not surprising that the medical community (simultaneously reflecting and shaping the culture) has tended to view the birth of intersexuals as abnormal mutations and medical emergencies. In fact, most of these “emergencies” are determined by cultural considerations.

The development of new medical technologies usually requires (or helps to construct) a scientific/cultural basis for their use. Such an influential rationale for contemporary surgical technology was provided by the work of the Hampsons, Money, and Ehrhardt. These scholars claimed that human sexuality was highly malleable. Money and his colleagues acknowledged that biological factors influenced the course of human sexual development, but they claimed that social learning had a more powerful effect. In essence, all children could be raised as either a boy or a girl, provided the sexual assignment was done within the first two years and adequate genitals could be constructed surgically. This research has provided the epistemic basis for the guidelines used by the American Association of Pediatricians over the past four decades.

The theory of psychosexual neutrality has not gone unchallenged. Research claiming a biological basis for human sexuality had begun in earnest during the second decade of the twentieth century and was well established during the 1950s and 1960s. In 1965, Diamond, Money’s most persistent and perceptive critic, published an article that raised serious questions regarding Money’s research. However, it took more than thirty years to discredit Money’s central ideas.

Perhaps the single most important event in this shift from Money’s ideas was Reimer’s (Money’s subject in the John/Joan case) decision to go public and refute Money’s fraudulent claims regarding the success of his case (Colapinto, 2000). Nevertheless, the American Association of Pediatricians still recommends surgical intervention and sex reassignment for infants born with ambiguous genitalia. Fausto-Sterling has joined with intersexual activists (e.g., Chase) in calling for an end to all such unnecessary infant surgery.

The impact of culture and politics on the production of scientific knowledge is well documented throughout Fausto-Sterling’s book. In chapter five, she provides a detailed account of the scientific attempt to verify the differences between males and females with regard to the section of the brain called the corpus callosum. Close examination of this research reveals an alarming number of methodological problems. Consequently, according to Fausto-Sterling, the representations of the corpus callosum found in the current research literature are literary fictions (p. 127). She is not opposed to this sort of research in principle but argues that we should be more sensitive regarding the extent to which such research has been inconclusive and shaped by prevailing cultural assumptions. She believes we would make more progress if we were to focus on individual differences and how “the brain develops as part of a social system” (p. 145).

In chapters six, seven, and eight, Fausto-Sterling traces the history of our conception of “sex hormones” and how this concept was applied to research on sex. By 1940, scientists had identified, named, and reached a general consensus on how to measure sex hormones and their effects. The new science of hormones, endocrinology, became enormously influential in the construction of the modern discourse on sexuality. As this research progressed, it became apparent that what were called sex hormones in fact played multiple roles and affected many areas of the body including the brain, liver, gall bladder, kidneys, blood cell formation, the circulatory system, lipid and carbohydrate metabolism, and muscle activities. However, the assumption that the sex hormones were gendered was deeply ingrained and difficult to abandon. Indeed, the etymology of the terms androgen (to build a man) and estrogen (to create estrus) illustrate the role played by sexual ideology.

An important example of how the course of research on sexuality has been shaped by cultural beliefs is illustrated by research on rodents from the 1930s to the present. Fausto-Sterling describes the development of Beach’s research and how his complex theory of animal sexuality was eventually replaced by the far narrower ideas of Young and his colleagues. Beach, the leading scholar in this area from the 1930s through the 1950s, was critical of what he believed were the unscientific assumptions of the main social learning theories popular during the 1940s and 1950s. He argued that biology had a more significant influence on sexual behavior. However, Beach’s theory was not reductionist. He believed that we had to study the complex interaction of the various physiological systems (e.g., hormones, brain, central nervous system) as they interacted to shape behavior. He also demonstrated the significant influence individual genetic differences within sex and species had on animal sexuality. In addition, Beach’s research documented the important effects context and experience had on sexual behavior. Another important finding was that adult bisexuality and homosexuality were natural, not abnormal behaviors.

In 1959, Young and his colleagues presented what came to be the dominant scientific view of sexual development. The new theory–the organizational/activational (O/A) model of hormone activity–held that “pre- or perinatal hormones organized central nervous tissue so that at puberty hormones could activate specific behaviors” (p. 214, italics in the original). The O/A theory presented a direct challenge to the psychosexual neutrality theory proposed by the Hampsons and Money.

Neither the Hampsons nor Money ever claimed that biology played no role in sexual development; they did argue that early social learning had a more powerful influence on the development of our sexuality. Thus, the debate between Young and his colleagues on one side and Money and his colleagues on the other was around the relative importance of nature versus nurture. This dispute was not trivial, but we should note that both groups accepted that sexual dimorphism was natural and that the nature/nurture dichotomy was the way to approach the issue. Over time, the O/A theory came to dominate research on human sexuality, although Money’s influence on the treatment of intersexuals continues into the present.

Fausto-Sterling claims that the rejection of Beach’s ideas and the shift to the O/A theory has had a negative impact on sexuality research and our understanding of human sexuality. As individual genetic differences (lab rodents were bred to eliminate such differences) and the effects of experience were excluded from the focus of O/A research, biology came to be seen as the foundation for sexual development. For some researchers, biology was the overriding cause of human sexuality. However, even those who believed that an interaction between nature and nurture best explained sexual development assumed that biology provided the basic foundation to be shaped by subsequent experience.

Fausto-Sterling argues that research on sexuality will remain constrained as long as we continue to accept the O/A mind/body dualism, which holds that the body (nature) is the fundamental precursor to behavior. She believes we need to switch our perspective “so that we see nature and nurture as an indivisible, dynamic system.” (p. 228). This is not, in her estimation, a new view, but one that has been neglected. She cites research (animal and human) to illustrate how the environment (including the prenatal environment) can change our anatomy, brain, and central nervous system. In this way, “events outside the body become incorporated into our very flesh” (p. 238).

Fausto-Sterling argues for a more flexible view of sex and sexuality, one that does not give primary signifying status to the genitals but allows an individual the right to redefine his/her sexual identity. She urges researchers to abandon terms such as sex hormones, androgen, and estrogen and to use the more accurate term steroid hormones instead. She also asks that we consider removing the category sex from our major forms of identification (e.g., driver’s license). While such proposals might seem radical to many, they are motivated by her research on the dysfunctional effects of our current views of sex and sexuality.
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Compared to other primates, humans take far longer to reach maturity. One can argue that the evolutionary benefit derived from remaining so long in such a vulnerable state comes from the increased opportunity for environment (cultural and physiological) to shape our behavior. Understanding this sort of dynamic system requires both a change of view and extensive research collaboration across disciplinary boundaries. Sexing the Body promotes the dialogue required to move in this direction. Fausto-Sterling claims to “have written two books in one: a narrative accessible to a general audience and a scholarly work intended to advance discussion and arguments within academic circles” (p. ix). She has succeeded on both counts.

REFERENCES

Colapinto, J. (2000). As nature made him: The boy who was raised as a girl. New York: HarperCollins.

Diamond, M. (1965). Critical evaluation of the ontogeny of human sexual behavior. Quarterly Review of Biology, 40, 147-175.

Dreger, A.D. (1998). Hermaphrodites and the medical invention of sex. Cambridge, MA: Harvard University Press.

Herdt, G. (Ed.). (1996). Third sex, third gender: Beyond sexual dimorphism in culture and history. New York: Zone Books.

Reviewed by William B. Stanley, University of Colorado at Boulder, School of Education,Education Building 124, Campus Box 249, Boulder, CO 80309; e-mail: wb.stanley@colorado.edu and Lynn W. Stanley, 1741 Lois Court, Lafayette, CO 80026; e-mail: wbs@colorado.edu.

COPYRIGHT 2001 Society for the Scientific Study of Sexuality, Inc.
COPYRIGHT 2001 Gale Group

Semen Ingredient ‘Drastically’ Enhances HIV Infection

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A plentiful ingredient found in human semen drastically enhances the ability of the human immunodeficiency virus (HIV) to cause infection. The findings of a recently published report help to understand the sexual transmission of HIV and suggest a potential new target for preventing the spread of AIDS, the researchers said.

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Collaborating research groups in Hannover and Ulm, Germany, show that naturally occurring fragments of so-called prostatic acidic phosphatase (PAP) isolated from human semen form tiny fibers known as amyloid fibrils. Those fibrils capture HIV particles and help them to penetrate target cells, thereby enhancing the infection rate by up to several orders of magnitude.

“We were not expecting to find an enhancer, and were even more surprised about the strength,” said Frank Kirchhoff of the University Clinic of Ulm, noting that they were initially looking for factors in semen that might help to block HIV infection. “Most enhancers have maybe a two- or three-fold effect, but here the effect was amazing–more than 50-fold and, under certain conditions, more than 100,000-fold. At first, I didn’t believe it, but we ran the experiment over and over, always with the same result.”

“The fibrils act like a ferry,” said Wolf-Georg Forssmann of VIRO PharmaCeuticals GmbH & Co. KG and Hannover Medical School. “They pick the viruses up and then bring them to the cell.”

HIV-1, the causative agent of AIDS, has infected about 60 million people and caused over 20 million deaths, the researchers said. More than 90 percent of those HIV-1 infections are acquired through sexual intercourse. Globally, most infections result from genital exposure to the semen of HIV-positive men, earlier studies showed. Women who acquired HIV-1 through vaginal intercourse constitute almost 60 percent of new infections in Africa. Yet the factors influencing the infectiousness of HIV in semen are poorly understood.

To identify natural agents that might play a role in sexual transmission of HIV/AIDS in the new study, the researchers sifted through a complex peptide/protein library derived from human seminal fluid in search of novel inhibitors and/or enhancers of HIV infection.

That comprehensive search turned up PAP fragments as a potent enhancer of HIV infection. They then verified that synthetic PAP fragments also enhanced HIV, confirming it as the active ingredient. Interestingly, they found that individual PAP fragments are inactive but efficiently form amyloid fibrils, which they call Semen-derived Enhancer of Virus Infection or SEVI, that enhance HIV-1 infection by capturing virions and promoting their physical interaction and fusion with target cells.

The enhancing activity of SEVI is most pronounced when the levels of infectious virus are low, resembling the conditions of sexual HIV-1 transmission, they reported. Physiological concentrations of SEVI amplified HIV infection of immune cells known as T cells and macrophages, most likely the cell types first targeted by HIV-1. SEVI lowered the amount of virus required to infect tissue taken from human tonsils and significantly enhanced the viral infection of transgenic rats with human receptors for HIV-1 infection.

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The researchers said they will continue to explore SEVI’s role in HIV transmission. While the peptide that conglomerates into fibrils is always present in large quantities in semen, they don’t yet know if the absolute levels vary from man to man. “We also plan to further explore how exactly the fibrils allow the virus to enter cells and to search for compounds, with our technology, that might block the process,” Forssmann said.

If such inhibitors can be found, they might be added to microbicide gels now under development for HIV prevention, added Kirchhoff. There could also be other ways to take advantage of the fibrils. “The high potency of SEVI in promoting viral infection together with its relatively low cytotoxicity suggests that it may not only play a relevant role in sexual HIV transmission, but could also help to improve vaccine approaches and gene delivery by lentiviral vectors,” the researchers said.

Cell, Vol 131, 1059-1071, 14 December 2007

Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

Jan Münch,1 Elke Rücker,1 Ludger Ständker,2,3 Knut Adermann,2,3,4 Christine Goffinet,5 Michael Schindler,11 Raghavan Chinnadurai,1 Devi Rajan,1 Anke Specht,1 Guillermo Giménez-Gallego,6 Pedro Cuevas Sánchez,7 Douglas M. Fowler,8 Atanas Koulov,8 Jeffery W. Kelly,8 Walther Mothes,9 Jean-Charles Grivel,1010 Oliver T. Keppler,5 Wolf-Georg Forssmann,2,3, and Frank Kirchhoff1, Steffen Wildum, Leonid Margolis,

1 Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany
2 IPF PharmaCeuticals GmbH, 30625 Hannover, Germany
3 Hannover Medical School, Center of Pharmacology, 30625 Hannover, Germany
4 VIRO Pharmaceuticals GmbH & Co. KG, 30625 Hannover, Germany
5 Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
6 Centro de Investigaciones Biológicas (CIB/CSIC), Madrid 28040, Spain
7 Hospital Ramón y Cajal, Madrid 28034, Spain
8 Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
9 Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
10 National Institute of Child Health and Human Development, Bethesda, MD 20892, USA

Corresponding author
Wolf-Georg Forssmann
wg.forssman@pharis.de

Corresponding author
Frank Kirchhoff
frank.kirchhoff@uniklinik-ulm.de


Summary


Sexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention.

Written by huehueteotl

December 14, 2007 at 3:45 pm

Risk Perception – Make Numbers Matter

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Putting Risk In Perspective: Do People Make Better Decisions When They Understand Average Risk?

If there were a pill that would cut your risk of breast cancer in half, would you take it” What if you were told your risk of breast cancer was already below average”

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In a newly published survey, women who were told their risk of breast cancer was above average were more likely to endorse taking the hypothetical pill than women who were told their risk was below average. The above average group was also more likely to believe that the pill significantly reduced breast cancer risk — even though both groups were told the pill would cut their risk of breast cancer in half.

Researchers from the University of Michigan Comprehensive Cancer Center surveyed 249 random women in a hospital cafeteria. Participants were given a scenario in which their own risk of breast cancer was 6 percent. Then, half of the women were told the average woman’s risk of breast cancer was 12 percent; the other half were told the average risk was 3 percent.

Both groups were told in the hypothetical scenario that there was a pill that would reduce their breast cancer risk to 3 percent, but it caused side effects including hot flashes in most women, with a small risk of cataracts, stroke or heart attack. They were then asked to say if they would take the pill, given their risk of breast cancer.

No matter what their decision, 62 percent of the women said the average risk information was helpful in making a decision about whether to take the drug.

But, the study authors contend, this influence could be dangerous. After all, if a prevention strategy reduces a person’s risk by half, does it matter if others receive more or less benefit”

“What’s really important is to focus on your risk and the benefits you could get from a treatment. Knowing how one’s own risk compared to the average woman’s risk actually changed people’s decisions. It’s very worrisome that this piece of information had an influential impact on a woman’s perceptions of a breast cancer prevention drug,” says study author Angela Fagerlin, Ph.D., research assistant professor of internal medicine at the U-M Medical School and an investigator at the VA Ann Arbor Healthcare System.

Results of the study appear in the December issue of Patient Education and Counseling.

The study authors argue that comparing individual risk against average could lead people to make poor decisions. For example, below-average risk does not mean zero risk, yet low-risk women might think they can skip their yearly mammogram. On the other hand, women at high-risk might undergo risky treatments that they might otherwise not have chosen.

“When you give women their five-year risk of breast cancer, it might be 3 percent, and that 3 percent seems really low. But the way women tend to use comparative information is worrisome. They’re focusing too much on where they stack up against average and they disregard their own individual risk information what that risk means to them,” says Fagerlin, a member of the U-M Center for Behavioral and Decision Sciences in Medicine.

The study authors urge doctors and health educators to use average risk carefully when discussing individual patients’ options.

“People should focus on what their own risk is — how does that risk feel to them, and what do they think of their treatment or prevention strategies. We believe that when making a medical decision, people should consider the risks and benefits of their prevention or treatment options and they should make the best decision based on their perceptions of those risks and benefits. The decision should not be influenced by whether their risks or benefits are greater or less than another person,” Fagerlin says.

The risk estimates used in the study were fictitious. The drug mentioned is modeled after tamoxifen, which can be given to women at high risk of breast cancer to help prevent the disease. The average woman’s lifetime risk of breast cancer is 12.7 percent, or one in eight. But an individual’s five-year risk of breast cancer will vary based on family history, environmental exposures and lifestyle issues. Some 178,480 women will be diagnosed with breast cancer this year and more than 40,000 will die from the disease.

Patient Educ Couns. 2007 Dec;69(1-3):140-144. Epub 2007 Oct 17.

“If I’m better than average, then I’m ok?”: Comparative information influences beliefs about risk and benefits.

Fagerlin A, Zikmund-Fisher BJ, Ubel PA.

VA Health Services Research & Development Center for Practice Management and Outcomes Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, United States; Division of General Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Center for Behavioral and Decision Sciences in Medicine, Ann Arbor, MI, United States.

OBJECTIVE: To test whether providing comparative risk information changes risk perceptions. METHODS: Two hundred and forty-nine female visitors to a hospital cafeteria were randomized to one of two conditions which differed in whether their hypothetical breast cancer risks was lower or higher than the average women’s. Participants read a scenario describing a breast cancer prevention pill and indicated their: (1) likelihood of taking the pill and (2) perception of whether the pill provides breast cancer risk reduction. RESULTS: Women told that their hypothetical risk of breast cancer was above average were more likely to endorse taking the pill (2.79 vs. 2.23, F=4.95, p=0.002) and more likely to believe that the pill provided a significant risk reduction in breast cancer (3.15 vs. 2.73, F=4.32, p=0.005), even though the risks were equivalent. CONCLUSIONS: Providing people with comparative risk information changes their risk perceptions. People who have above average risk may feel compelled to take a treatment because they are at above average risk and therefore may not thoroughly consider the trade-offs in the risks and benefits of treatment. PRACTICE IMPLICATIONS: Physicians and decision aid developers must reconsider the practice of communicating “average risk” information to patients.

see also:

Am J Health Behav. 2007 Sep-Oct;31 Suppl 1:S47-56.

Making numbers matter: present and future research in risk communication.

Fagerlin A, Ubel PA, Smith DM, Zikmund-Fisher BJ.

Ann Arbor VA HSR&D Center for Excellence, Division of General Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0429, USA. fagerlin@umich.edu

OBJECTIVE: To summarize existing research on individual numeracy and methods for presenting risk information to patients. METHODS: We selectively retrieved articles from MEDLINE and the Social Sciences Citation Index. RESULTS: Many Americans have low numeracy skills, a deficit that impedes effective health care. Approaches to risk communication vary in current practice, but how risks are presented can significantly affect both patients’ risk perceptions and their knowledge. CONCLUSIONS: Adhering to some basic principles for presenting risk information to patients can improve understanding. However, different risk-communication methods may be needed for individuals with high versus low levels of numeracy.

Written by huehueteotl

December 14, 2007 at 1:04 pm

Truth May Be Beauty, And Beauty Truth…

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and false propositions may actually disgust us. Different areas of the brain respond to belief, disbelief and uncertainty.

The human mind is a prolific generator of beliefs about the world. The capacity of our minds to believe or disbelieve linguistic propositions is a powerful force for controlling both behavior and emotion, but the basis of this process in the brain is not yet understood.

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Sam Harris, a UCLA graduate student in the lab of Mark Cohen, a professor of psychiatry at the UCLA Center for Cognitive Neuroscience and a study co-author, and Sameer Sheth of Massachusetts General Hospital, report another functional magnetic resonance imaging (fMRI) study, that would reveal clear differences in the areas of the brain involved in belief, disbelief and uncertainty.

Their results suggest that the differences among these cognitive states may one day be distinguished reliably, in real time, by techniques of neuroimaging. This finding has implications for the detection of deception, for the control of the placebo effect during drug design and for the study of any higher cognitive phenomenon in which the differences among belief, disbelief and uncertainty might be relevant.

Fourteen adult volunteers were scanned in an MRI device at UCLA’s Brain Imaging Center. While inside the scanner, subjects were presented with written statements covering a broad range of topics, including mathematics, geography, factual knowledge, word definitions, religion, ethics and biographical facts about themselves. Subjects were asked to rate these statements as true, false or undecidable. The authors then compared the brain images recorded when their subjects believed, disbelieved or could not judge the truth-value of these written propositions.

The scientists predicted that the difference between belief and disbelief would be largely mediated by activity in the frontal lobes — the part of the brain most enlarged and differentiated in humans. Indeed, when belief and disbelief were compared, the investigators saw differences principally in a region known as the ventromedial prefrontal cortex (VMPFC), near the front of the brain, along its midline.

“The involvement of the VMPFC in belief processing suggests an anatomical link between the purely cognitive aspects of belief and human emotion and reward,” the authors said. “The fact that ethical belief showed a similar pattern of activation to mathematical belief suggests that the physiological difference between belief and disbelief may be independent of content or emotional associations.”

The areas especially engaged in disbelief included the limbic system’s cingulate areas and the anterior insula, a brain region known to report visceral sensations such as pain and disgust and to be involved largely in negative appraisals of sensations like taste and smell.

“Our results appear to make sense of the emotional tone of disbelief, placing it on a continuum with other modes of stimulus appraisal and rejection,” the authors said. “False propositions might actually disgust us.”

When the subjects experienced uncertainty, yet another pattern emerged. A different portion of the cingulate cortex, located closer to the front of the brain, showed a much stronger signal. This so-called “anterior cingulate” cortex frequently shows up in studies of conflict monitoring, error detection and cognitive interference. When compared to both belief and disbelief, the state of uncertainty also showed a decreased signal in the caudate, a region of the basal ganglia, which plays a role in motor action.

Noting that uncertainty differs from both belief and disbelief by not allowing us to settle upon “a specific, actionable interpretation of the world,” the authors suggest that the basal ganglia may play a role in mediating the cognitive and behavioral differences between decision and indecision.

Taken together, these data offer insight into the way in which our brains work to form beliefs about the world.

“What I find most interesting about our results is the suggestion that our view of the world must pass through a bottleneck in regions of the brain generally understood to govern emotion, reward and primal feelings like pain and disgust,” Harris said. “While evaluating mathematical, ethical or factual statements requires very different kinds of processing, accepting or rejecting these statements seems to rely upon a more primitive process that may be content-neutral. I think that it has long been assumed that believing that two plus two equals four and believing that George Bush is President of the United States have almost nothing in common as cognitive operations. But what they clearly have in common is that both representations of the world satisfy some process of truth-testing that we continually perform. I think this is yet another result, in a long line of results, that calls the popular opposition between reason and emotion into question.”

Ann Neurol. 2007 Dec 10 [Epub ahead of print]

Functional neuroimaging of belief, disbelief, and uncertainty.

Harris S, Sheth SA, Cohen MS.

University of California Los Angeles Brain Mapping Center, Los Angeles, CA.

OBJECTIVE: The difference between believing and disbelieving a proposition is one of the most potent regulators of human behavior and emotion. When one accepts a statement as true, it becomes the basis for further thought and action; rejected as false, it remains a string of words. The purpose of this study was to differentiate belief, disbelief, and uncertainty at the level of the brain. METHODS: We used functional magnetic resonance imaging (fMRI) to study the brains of 14 adults while they judged written statements to be “true” (belief), “false” (disbelief), or “undecidable” (uncertainty). To characterize belief, disbelief, and uncertainty in a content-independent manner, we included statements from a wide range of categories: autobiographical, mathematical, geographical, religious, ethical, semantic, and factual. RESULTS: The states of belief, disbelief, and uncertainty differentially activated distinct regions of the prefrontal and parietal cortices, as well as the basal ganglia. INTERPRETATION: Belief and disbelief differ from uncertainty in that both provide information that can subsequently inform behavior and emotion. The mechanism underlying this difference appears to involve the anterior cingulate cortex and the caudate. Although many areas of higher cognition are likely involved in assessing the truth-value of linguistic propositions, the final acceptance of a statement as “true” or its rejection as “false” appears to rely on more primitive, hedonic processing in the medial prefrontal cortex and the anterior insula. Truth may be beauty, and beauty truth, in more than a metaphorical sense, and false propositions may actually disgust us. Ann Neurol 2007.

Written by huehueteotl

December 13, 2007 at 4:00 pm