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Archive for January 2008

Circuitry Of Feedback Perception

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Researchers have found the brain region that controls the decision to halt your midnight exploration of the refrigerator and commence enjoyment of that leftover chicken leg. What’s more, they said, such mechanisms governing exploration are among those that malfunction in addiction and mental illness.
In their experiments, the researchers presented monkeys with a choice of touch targets on a computer screen, requiring the monkeys to spend time exploring which target would trigger a juice reward. Once the monkeys discovered the reward target, the researchers then gave the animals a period during which they could repeatedly touch the reward target to obtain more juice.

During the trials, the researchers recorded the electrical activity of hundreds of neurons in the anterior cingulate cortex (ACC), a brain region known to be active in adaptive behaviors such as the shift between exploring and exploiting.

In their analysis, the researchers measured the electrophysiological activity of cells during four different types of feedback–incorrect choices, first reward, repetition of the reward, and the ending of a trial by breaking fixation on the targets.

Analyzing the results, the researchers concluded that “Our data show that ACC discriminates between different types of feedback, allowing appropriate behavioral adaptations.”

Emmanuel Procyk and colleagues published their findings in the January 24, 2008, issue of the journal Neuron, published by Cell Press.

They wrote that “Thus, the function we attribute to ACC activations is clearly not only to evaluate feedbacks but is also to participate in monitoring the different steps of the task at hand to optimize action adaptation and valuation. A dysfunction of these mechanisms represents the core feature of cognitive alterations observed in addiction and mental illness.”

Wrote Procyk and colleagues, “The ACC produces signals that discriminate between various behaviorally relevant positive and negative feedbacks, suggesting a role in triggering appropriate adaptations. Our data reinforce the proposal that ACC is important for establishing action valuations. But they also emphasize a combined role in monitoring events/actions for behavioral regulation when task control is high, underlining the intimate link between control and action valuation.”

Neuron. 2008 Jan 24;57(2):314-25.
Behavioral shifts and action valuation in the anterior cingulate cortex.

Inserm, U846, Stem Cell and Brain Research Institute, 69500 Bron, France; Université de Lyon, Lyon 1, UMR-S 846, 69003 Lyon, France.

Rapid optimization of behavior requires decisions about when to explore and when to exploit discovered resources. The mechanisms that lead to fast adaptations and their interaction with action valuation are a central issue. We show here that the anterior cingulate cortex (ACC) encodes multiple feedbacks devoted to exploration and its immediate termination. In a task that alternates exploration and exploitation periods, the ACC monitored negative and positive outcomes relevant for different adaptations. In particular, it produced signals specific of the first reward, i.e., the end of exploration. Those signals disappeared in exploitation periods but immediately transferred to the initiation of trials-a transfer comparable to learning phenomena observed for dopaminergic neurons. Importantly, these were also observed for high gamma oscillations of local field potentials shown to correlate with brain imaging signal. Thus, mechanisms of action valuation and monitoring of events/actions are combined for rapid behavioral regulation

Written by huehueteotl

January 28, 2008 at 12:50 pm

Sense Of Injustice Reverses Effects Of Power

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Power is intoxicating, but feelings of injustice soon sober up the one with the power. PhD student Joris Lammers investigated the role that the meaning of a power situation has on the automatic effects of power. In his thesis he concludes that feelings of injustice reverse the automatic effects of power on behaviour and cognition. The one with the power becomes more careful and the subordinate displays more uncontrolled behaviour.

According to the standard opinion in social psychology, power has a liberating effect and makes the one with the power impulsive whereas lack of power has a numbing effect and makes people passive. Lammers wanted to know whether the meaning of the power situation also played a role.

Power situations

He investigated power effects by having students describe a situation in which they felt powerful or powerless, and then getting them to perform assignments. The power situations described could be experienced as just (someone elected president of the student’s union) or as unjust (a ragging situation). The assignments involved playing betting games or solving invented problems. In situations perceived as just, the test subjects with a powerful ‘state of mind’ turned out to bet significantly more and powerless subjects more often chose the safe option. However, if the power was perceived as unjust, these effects reversed and it was the ones with the power who played safe while the powerless subjects made more risky choices.

Zacht’ or ‘zucht’

An earlier experiment had revealed that people in lower power positions were more occupied with the question of what the person in power thought about them and were more inclined to attribute stereotypical thoughts they had about themselves to the one in power. Women who in a role play with a man played the subordinate role subsequently more often chose in tests to complete the letter combination Z*CHT with ‘zacht’ (soft, with feminine associations) than with ‘zucht’, ‘zicht’ or ‘zocht’ (sigh, sight or searched, respectively; neutral). Women in positions of power turned out not to be concerned with what the subordinate man thought about them. They randomly filled in ‘zucht’, ‘zicht’, ‘zacht’ or ‘zocht’. Lammers: ‘These results are logical. If you are in a subordinate position, it’s important to know what your boss thinks of you.’


Lammers also investigated cooperation. According to the standard view, powerful people are less inclined towards cooperation, whereas powerless people eagerly seek cooperation. Via experiments, Lammers concludes that this effect reverses completely if the power is viewed as unjust. In a position of power unjustly acquired, the people with the power were eager to cooperate whereas the subordinate people were not.

Tasty soup

Feelings of injustice in a power situation, according to Lammers, could lead to the ‘manager becoming paralysed and the cook spitting into the soup’. An employee further down the ladder cooperates best if he or she views his own position as justified. An employee higher up the ladder is more inclined to cooperate if he or she views his power position as unjust or not evident. Therefore, if the cook receives sufficient valuation for his work, he will find the power of the restaurant owner just. In that situation he will choose security and cooperation instead of reckless opposition.

Toward a more social social psychology of power

Joris Lammers.

[S.l. : s.n.], 2008. – 112 p. : tab. ; 24 cm. – (Dissertatiereeks / Kurt Lewin Instituut ; 2008-8) Proefschrift Rijksuniversiteit Groningen. – Met lit.opg. – Met samenvatting in het Nederlands. ISBN 978-90-5335-150-5

In this dissertation I aim to take a step toward a more social social psychology of power. In my opinion the existing social psychology on power is insufficiently social, and too material and physical. I believe this material and physical view has greatly influenced how social psychology has studied and tried to understand and conceptualize power. This view has however problematic aspects that can limit our understanding of power.

Written by huehueteotl

January 28, 2008 at 12:44 pm

New Experimental Website Converts Photos Into 3D Models

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An artist might spend weeks fretting over questions of depth, scale and perspective in a landscape painting, but once it is done, what’s left is a two-dimensional image with a fixed point of view. But the Make3d algorithm, developed by Stanford computer scientists, can take any two-dimensional image and create a three-dimensional “fly around” model of its content, giving viewers access to the scene’s depth and a range of points of view.

Maui coast, Hawaii. A new program created by Stanford computer scientists, can take any two-dimensional image and create a three-dimensional “fly around” model of its content, giving viewers access to the scene’s depth and a range of points of view. (Credit: Michele Hogan)

“The algorithm uses a variety of visual cues that humans use for estimating the 3-D aspects of a scene,” said Ashutosh Saxena, a doctoral student in computer science who developed the Make3d website with Andrew Ng, an assistant professor of computer science. “If we look at a grass field, we can see that the texture changes in a particular way as it becomes more distant.”

The applications of extracting 3-D models from 2-D images, the researchers say, could range from enhanced pictures for online real estate sites to quickly creating environments for video games and improving the vision and dexterity of mobile robots as they navigate through the spatial world.

Extracting 3-D information from still images is an emerging class of technology. In the past, some researchers have synthesized 3-D models by analyzing multiple images of a scene. Others, including Ng and Saxena in 2005, have developed algorithms that infer depth from single images by combining assumptions about what must be ground or sky with simple cues such as vertical lines in the image that represent walls or trees. But Make3d creates accurate and smooth models about twice as often as competing approaches, Ng said, by abandoning limiting assumptions in favor of a new, deeper analysis of each image and the powerful artificial intelligence technique “machine learning.”

Restoring the third dimension

To “teach” the algorithm about depth, orientation and position in 2-D images, the researchers fed it still images of campus scenes along with 3-D data of the same scenes gathered with laser scanners. The algorithm correlated the two sets together, eventually gaining a good idea of the trends and patterns associated with being near or far. For example, it learned that abrupt changes along edges correlate well with one object occluding another, and it saw that things that are far away can be just a little hazier and more bluish than things that are close.

To make these judgments, the algorithm breaks the image up into tiny planes called “superpixels,” which are within the image and have very uniform color, brightness and other attributes. By looking at a superpixel in concert with its neighbors, analyzing changes such as gradations of texture, the algorithm makes a judgment about how far it is from the viewer and what its orientation in space is. Unlike some previous algorithms, the Stanford one can account for planes at any angle, not just horizontal or vertical. This allows it to create models for scenes that have planes at many orientations, such as the curved branches of trees or the slopes of mountains.

On the Make3d website, the algorithm puts images uploaded by users into a processing queue and will send an e-mail when the model has been rendered. Users can then vote on whether the model looks good, and can see an alternative rendering and even tinker with the model to fix what might not have been rendered right the first time.

Photos can be uploaded directly or pulled into the site from the popular photo-sharing site Flickr.

Although the technology works better than any other has so far, Ng said, it is not perfect. The software is at its best with landscapes and scenery rather than close-ups of individual objects. Also, he and Saxena hope to improve it by introducing object recognition. The idea is that if the software can recognize a human form in a photo it can make more accurate distance judgments based on the size of the person in the photo.

A paper on the algorithm by Ng, Saxena and a fellow student, Min Sun, won the best paper award at the 3-D recognition and reconstruction workshop at the International Conference on Computer Vision in Rio de Janeiro in October 2007.

For many panoramic scenes, there is still no substitute for being there. But when flat photos become 3-D, viewers can feel a little closer—or farther. The algorithm runs at

Source: ScienceDaily (Jan. 26, 2008)

Written by huehueteotl

January 26, 2008 at 6:06 pm

Price Tag Can Change The Way People Experience Wine

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… a study shows for 11 californian male Caltech graduate students. Californians cannot tell price from taste, when it comes to whine. Certain californian wines do taste like that. And the old adage that you get what you pay for really seems then most true.

In what will be music to the ears of marketers, the old adage that you get what you pay for really is true when it comes to that most ephemeral of products: bottled wine.

If a person is told he or she is tasting two different wines–and that one costs $5 and the other $45 when they are, in fact, the same wine–the part of the brain that experiences pleasure will become more active when the drinker thinks he or she is enjoying the more expensive vintage. (Credit: iStockphoto/Joey Nelson)

According to researchers at the Stanford Graduate School of Business and the California Institute of Technology, if a person is told he or she is tasting two different wines—and that one costs $5 and the other $45 when they are, in fact, the same wine—the part of the brain that experiences pleasure will become more active when the drinker thinks he or she is enjoying the more expensive vintage.

“What we document is that price is not just about inferences of quality, but it can actually affect real quality,” said Baba Shiv, a professor of marketing who co-authored a paper titled “Marketing Actions Can Modulate Neural Representations of Experienced Pleasantness,” published online Jan. 14 in the Proceedings of the National Academy of Sciences. “So, in essence, [price] is changing people’s experiences with a product and, therefore, the outcomes from consuming this product.”

Shiv, an expert in how emotion affects decision-making, used functional magnetic resonance imaging (fMRI) to conduct the study with co-authors Hilke Plassmann, a former Stanford postdoctoral researcher; Antonio Rangel, a former Stanford economist; and psychologist John O’Doherty. (Both Plassmann and Rangel are now at Caltech.) Although researchers have used fMRI scans in recent years to gauge brain activity, the study is one of the first to test subjects as they swallow liquid—in this case, wine—through a pump attached to their mouths, a tricky complication because the scanner requires people to lie very still as it measures blood flow in the brain.

According to Shiv, a basic assumption in economics is that a person’s “experienced pleasantness” (EP) from consuming a product depends only on its intrinsic properties and the individual’s thirst. However, marketers try to influence this experience by changing a drink’s external properties, such as its price. “This type of influence is valuable for companies, because EP serves as a learning signal that is used by the brain to guide future choices,” the paper says. Contrary to this basic assumption, several studies have shown that marketing can influence how people value goods. For example, Shiv has shown that people who paid a higher price for an energy drink, such as Red Bull, were able to solve more brain teasers than those who paid a discounted price for the same product.

Despite the pervasive influence of marketing, very little is known about how neural mechanisms affect decision-making, the researchers said. “Here, we propose a mechanism though which marketing actions can affect decision-making,” they write. “We hypothesized that changes in the price of a product can influence neural computations associated with EP.” Because perceptions about quality are positively correlated with price, the scholars argued that someone might expect an expensive wine to taste better than a cheaper one. Their hypothesis went further, stipulating that a person’s anticipated experience would prompt higher activity in the part of the brain that experiences pleasure, the medial orbitofrontal cortex, or mOFC, in the forehead.

Shiv, a native of India, said he decided to study wine because so many people, especially in the Golden State, are crazy about it. “I’m just fascinated with wine,” he said. “It has always amused me how much time and effort people put into this hobby. I couldn’t understand it until I moved to California and started appreciating the whole thing. But, in the back of my mind, the price variation in wines has always puzzled me. You can go from spending $4 to $200 to $300 and up a bottle. Why are people going for that? Some are trying to show off, but most people are not. They are very serious about it, and they think that the more expensive it is, the better it is. That has always befuddled me. Is it really that people are getting more pleasure from it? Or do they just think so?”

The study

The researchers recruited 11 male Caltech graduate students who said they liked and occasionally drank red wine. The subjects were told that they would be trying five different Cabernet Sauvignons, identified by price, to study the effect of sampling time on flavor. In fact, only three wines were used—two were given twice. The first wine was identified by its real bottle price of $5 and by a fake $45 price tag. The second wine was marked with its actual $90 price and by a fictitious $10 tag. The third wine, which was used to distract the participants, was marked with its correct $35 price. A tasteless water was also given in between wine samples to rinse the subjects’ mouths. The wines were given in random order, and the students were asked to focus on flavor and how much they enjoyed each sample.


The participants said they could taste five different wines, even though there were only three, and added that the wines identified as more expensive tasted better. The researchers found that an increase in the perceived price of a wine did lead to increased activity in the mOFC because of an associated increase in taste expectation. Shiv said he expects enophiles will challenge the results, since his subjects were not professional connoisseurs. “Will these findings replicate among experts?” he asked. “We don’t know, but my speculation is that, yes, they will. I expect that the enophiles will show more of these effects, because they really care about it.”

According to Shiv, the emotional and hedonic areas of the brain could be fundamental to making good decisions because they serve as a navigational device. “The brain is super-efficient,” he said. “There seems to be this perfect overlap in one part of the brain between what happens in real time and what happens when people anticipate something. It’s almost acting as a GPS system. This seems to be the navigational device that helps us learn what is the right thing to do the next time around.”

Published online before print January 14, 2008, 10.1073/pnas.0706929105
PNAS | January 22, 2008 | vol. 105 | no. 3 | 1050-1054
Marketing actions can modulate neural representations of experienced pleasantness
Hilke Plassmann*, John O’Doherty*, Baba Shiv and Antonio Rangel*

*Division of the Humanities and Social Sciences, California Institute of Technology, MC 228-77, Pasadena, CA 91125; and Stanford Graduate School of Business, Stanford University, 518 Memorial Way, Littlefield L383, Stanford, CA94305

Edited by Leslie G. Ungerleider, National Institutes of Health, Bethesda, MD, and approved December 3, 2007 (received for review July 24, 2007)

Despite the importance and pervasiveness of marketing, almost nothing is known about the neural mechanisms through which it affects decisions made by individuals. We propose that marketing actions, such as changes in the price of a product, can affect neural representations of experienced pleasantness. We tested this hypothesis by scanning human subjects using functional MRI while they tasted wines that, contrary to reality, they believed to be different and sold at different prices. Our results show that increasing the price of a wine increases subjective reports of flavor pleasantness as well as blood-oxygen-level-dependent activity in medial orbitofrontal cortex, an area that is widely thought to encode for experienced pleasantness during experiential tasks. The paper provides evidence for the ability of marketing actions to modulate neural correlates of experienced pleasantness and for the mechanisms through which the effect operates.

Written by huehueteotl

January 26, 2008 at 6:01 pm

While Shopping Mind What You Do

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Your shopping buddy turns to you and asks, “Which one of these would you get?” Or, you’re talking with your spouse about which candidate you’d like to vote for before switching on the nightly news. Turns out simply being asked to make a choice– especially if you’re in a hurry or have something on your mind — will make you like the next thing you see more, says a new study from the Journal of Consumer Research. The researchers found that asking people to choose among things primed them to think about positive attributes — and caused them to be in a positive frame of mind when evaluating the next item they saw.

“Simply asking participants to decide if they would buy (vs. reject) each of a set of products disposed them to search for favorable attributes before unfavorable ones in an unrelated product evaluation situation,” explain Hao Shen and Robert S. Wyer, Jr. (both of the Hong Kong University of Science and Technology). “As a result, they evaluated the product they considered in the second situation more favorably than they otherwise would.”

The study expands our understanding of “memory priming.” As the researchers explain, our knowledge about a product or service usually involves norms — such as typical prices, typical amenities, and brand reputation associated with, say, a hotel. However, the researchers also reveal that this prior knowledge can be influenced by “procedural knowledge priming,” or, by introducing consumers to an activity that affects what they evaluate.

In another experiment, the researchers had participants in Hong Kong rank the prices of hotel rooms in three cities either from high-to-low or low-to-high. They were then asked to indicate how much they would pay for a hotel room, among other questions. When a lot of information was presented, those who ranked the prices from most expensive to least expensive were willing to pay an average of $19 more than those who had been asked to rank the hotels from lowest to highest priced.

In addition, “participants estimated the average price of hotel rooms in a city to be higher if they had rank[ed] prices from highest to lowest in a prior task than if they had ranked them from lowest to highest,” the researchers explain.

They continue: “Unrelated experiences can activate a search process that governs the order in which favorable and unfavorable product descriptions are identified and the evaluations that are made on the basis of them.”

© 2008 by JOURNAL OF CONSUMER RESEARCH, Inc. • Vol. 34 • February 2008
All rights reserved. 0093-5301/2008/3405-0008$10.00
DOI: 10.1086/523292
Procedural Priming and Consumer Judgments: Effects on the Impact of Positively and Negatively Valenced Information

Hao She, Robert S. Wyer Jr.*

Electronically published October 5, 2007

  • *Hao Shen () is a doctoral student, and Robert S. Wyer Jr. () is a visiting professor, in the Department of Marketing, Hong Kong University of Science and Technology. The authors thank the editor, associate editor, and reviewers, as well as Jaideep Sengupta and Rami Zwick for their comments on an earlier version of the manuscript. This research was supported in part by grants HKUST6053/01H, HKUST6194/04H, and HKUST6192/04H from the Research Grants Council, Hong Kong. Correspondence on the manuscript should be sent to Hao Shen.

The cognitive procedure that people use to search for information about a product is influenced by the ease with which it comes to mind. Unrelated experiences can activate a search process that governs the order in which favorable and unfavorable product descriptions are identified and the evaluations that are made on the basis of them. Five experiments examined the conditions in which these effects occur. The effects of priming a search strategy on the attention to positively or negatively valenced information are diametrically opposite to the effects of the semantic (e.g., attribute) concepts that are called to mind in the course of activating this strategy.

John Deighton served as editor and Geeta Menon served as associate editor for this article.

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January 25, 2008 at 4:22 pm

Giving Up Marijuana Feels As Bad As Giving Up Cigarettes

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Research by a group of scientists studying the effects of heavy marijuana use suggests that withdrawal from the use of marijuana is similar to what is experienced by people when they quit smoking cigarettes: bad feeling, but no real withdrawal. Abstinence from each of these drugs appears to cause several common symptoms, such as irritability, anger and trouble sleeping – based on self reporting in a recent study of 12 (!) heavy users of both marijuana and cigarettes. The authors recognize that the small sample size is a limitation in this study, but the results are consistent with other studies indicating that marijuana withdrawal effects are clinically important. And, they are not surprising, given that any forced change of habits does lead to similar complaints.

“These results indicate that some marijuana users experience withdrawal effects when they try to quit, and that these effects should be considered by clinicians treating people with problems related to heavy marijuana use,” says lead investigator in the study, Ryan Vandrey, Ph.D., of the Department of Psychiatry at the Johns Hopkins University School of Medicine.

Marijuana is the most widely used illicit drug in the United States. Admissions in substance abuse treatment facilities in which marijuana was the primary problem substance have more than doubled since the early 1990s and now rank similar to cocaine and heroin with respect to total number of yearly treatment episodes in the United States, says Vandrey.

He points out that a lack of data, until recently, has led to cannabis withdrawal symptoms not being characterized or included in medical reference literature such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV) or the International Classification of Diseases, 10th edition (ICD-10).

Since the drafting of the DSM-IV in 1994, an increasing number of studies have surfaced suggesting that cannabis has significant withdrawal symptoms. What makes Vandrey’s recent study unique is that it is the first study that compares marijuana withdrawal symptoms to withdrawal symptoms that are clinically recognized by the medical community – specifically the tobacco withdrawal syndrome.

“Since tobacco withdrawal symptoms are well documented and included in the DSM-IV and the IDC-10, we can infer from the results of this comparison that marijuana withdrawal is also clinically significant and should be included in these reference materials and considered as a target for improving treatment outcomes,” says Vandrey.

Vandrey added that this is the first “controlled” comparison of the two withdrawal syndromes in that data was obtained using rigorous scientific methods – abstinence from drugs was confirmed objectively, procedures were identical during each abstinence period, and abstinence periods occurred in a random order. That tobacco and marijuana withdrawal symptoms were reported by the same participants, thus eliminating the likelihood that results reflect physiological differences between subjects, is also a strength of the study.

Interestingly, the study also revealed that half of the participants found it easier to abstain from both substances than it was to stop marijuana or tobacco individually, whereas the remaining half had the opposite response.

“Given the general consensus among clinicians that it is harder to quit more than one substance at the same time, these results suggest the need for more research on treatment planning for people who concurrently use more than one drug on a regular basis,” says Vandrey.

Vandrey’s study, which appears in the January issue of the journal Drug and Alcohol Dependence, followed six men and six women at the University of Vermont in Burlington and Wake Forest University School of Medicine in Winston-Salem, N.C., for a total of six weeks. All were over 18 (median age 28.2 years), used marijuana at least 25 days a month and smoked at least 10 cigarettes a day. None of the subjects intended to quit using either substance, did not use any other illicit drugs in the prior month, were not on any psychotropic medication, did not have a psychiatric disorder, and if female, were not pregnant.

For the first week, participants maintained their normal use of cigarettes and marijuana. For the remaining five weeks, they were randomly chosen to refrain from using either cigarettes, marijuana or both substances for five-day periods separated by nine-day periods of normal use. In order to confirm abstinence, patients were given daily quantitative urine toxicology tests of tobacco and marijuana metabolites.

Withdrawal symptoms were self reported on a daily basis Monday through Friday using a withdrawal symptom checklist that listed scores for aggression, anger, appetite change, depressed mood, irritability, anxiety/nervousness, restlessness, sleep difficulty, strange dreams and other, less common withdrawal symptoms. Patients also provided an overall score for discomfort they experienced during each abstinence period.

Results showed that overall withdrawal severity associated with marijuana alone and tobacco alone was of similar frequency and intensity. Sleep disturbance seemed to be more pronounced during marijuana abstinence, while some of the general mood effects (anxiety, anger) seemed to be greater during tobacco abstinence. In addition, six of the participants reported that quitting both marijuana and tobacco at the same time was more difficult than quitting either drug alone, whereas the remaining six found that it was easier to quit marijuana or cigarettes individually than it was to abstain from the two substances simultaneously.

Drug Alcohol Depend. 2008 Jan 1;92(1-3):48-54. Epub 2007 Jul 23.

A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances.

Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

A cannabis withdrawal syndrome has been characterized, but its clinical significance remains uncertain. One method of assessing the significance of cannabis withdrawal is to compare it directly to an established withdrawal syndrome. The present study was a within-subject comparison of cannabis, tobacco, and combined cannabis and tobacco withdrawal among users of both substances. Participants (N=12) completed three 5-day periods of abstinence in a randomized order, separated by 9-day periods of usual substance use. Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted. These results are consistent with other evidence suggesting cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11. Additional research is needed to replicate these findings and to further investigate the effects of abstaining from multiple drugs simultaneously

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January 25, 2008 at 4:13 pm

Protein Glues HIV To The Spot Like Fly Strip

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In a study that could open up the field of virology to an entirely new suite of possibilities and that paves the way for future drug research, scientists at Rockefeller University and the Aaron Diamond AIDS Research Center have pinned down a molecule on the surface of human cells that helps keep particles of mutant strains of HIV from spreading. Rather than floating off to infect more cells, the protein contains the virus particles by keeping them attached to the parent cell’s outer membrane, as if stuck there with glue.

Sticky situation. HIV-1 particles (dark circles) lacking Vpu are unable to extricate themselves from the surface of their host cell. Instead, tetherin keeps them locked to the surface of the cell’s outer membrane, or causes them to be sucked back in and digested by the cell’s endosomes. (Credit: Image courtesy of Rockefeller University)
Two years ago, Paul Bieniasz — head of the Laboratory of Retrovirology and ADARC scientist — discovered that normal HIV-1 particles are able to extricate themselves from the sticky membrane surface using a protein called Vpu. Bieniasz has been searching for the source of the glue itself ever since. Now, in an advanced online publication in Nature, he and his colleagues report that they found it: a protein they dubbed “tetherin” for its ability to keep viruses tied to a cell.

“All we knew when we started this two and a half years ago was that a virus lacking Vpu was released less efficiently from cells.” Bieniasz says. “And we had some electron micrographs that showed virus particles stuck there on the surface and clustered inside cells.” Once they started looking carefully at the reasons behind this, they found an antiviral mechanism keeping the HIV-1 mutant particles tethered to the cell. And it wasn’t just HIV — the glue appeared to interfere with the spread of other membrane-encapsulated (or “enveloped”) viruses, too.

To track down the cause of stickiness — and the likely reason HIV evolved Vpu — Bieniasz and his team looked at gene activity across all known human genes, making comparisons between cells that require Vpu for HIV-1 release and those that don’t. Ultimately, they narrowed it down to one very likely candidate. And the candidate, the tetherin protein, passed all the tests the researchers threw at it: When Vpu was not present but tetherin was, large numbers of virus particles piled up on the cell surface. When tetherin was missing, however, even the Vpu-deficient viruses were able to escape.

“We’ve discovered a new way that cells defend themselves against viruses,” Bieniasz says. “I think this will open up a new area of study in virology: how this protein antagonizes other viruses, and how viruses learn to get around it.” Going forward, his lab will focus on how broad tetherin’s antiviral activity is, and whether variations of it exist that might confer additional immunity or sensitivity to HIV and other viruses. And, he notes, if drug researchers are able to interfere with the interaction between tetherin and Vpu, their newly discovered protein might even provide a potential therapeutic target.

Nature. 2008 Jan 24;451(7177):425-30. Epub 2008 Jan 16.
Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu.

Aaron Diamond AIDS Research Center and Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, New York 10016, USA.

Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term ‘tetherins’, that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin’s antiviral activity is a potential therapeutic strategy in HIV/AIDS.

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January 25, 2008 at 4:01 pm