D-1mT May Help HIV Patients Not Responding To Treatment In The Future

Monkeys with the simian form of HIV treated with a molecule called D-1mT alongside Anti-Retroviral Therapy (ART) reduced their virus levels in the blood to undetectable levels.

Simian Immunodeficiency Virus (SIV) is very similar to Human Immunodeficiency Virus (HIV) and it is used to study the condition in animal models. In both HIV and SIV, the level of virus in the blood, or ‘viral load’, is important because when the viral load is high, the disease progresses and it depletes the patient’s immune system. This eventually leads to the onset of Acquired Immune Deficiency Syndrome (AIDS), where the patient cannot fight infections which would be innocuous in healthy individuals.

Currently, the ‘gold standard’ treatment for HIV is Highly Active Anti-Retroviral Therapy (HAART), a cocktail of drugs that reduces the viral load by stopping the virus from replicating. HAART can increase the life expectancy of an HIV-positive patient substantially if it works well. However, the treatment is not effective for around one in ten patients, partly because some develop resistance to the drugs used in HAART. The researchers, from Imperial College London, the National Cancer Institute, Bethesda, and Innsbruck Medical University, hope their study could ultimately lead to a new treatment that will help HAART to work more effectively in these people.

In the new study, researchers gave daily doses of a modified amino acid called D-1mT to 11 rhesus macaques infected with SIV. All of the macaques had been treated with ART for at least four months. Eight of the macaques had higher viral loads (reaching up to 100,000 copies of the virus per millilitre of blood), because they were not responding completely to the treatment. However, three had undetectable viral loads (fewer than 50 copies of the virus per millilitre of blood), because ART was working well.

The researchers took blood samples at six and 13 days. After six days, only three of the macaques had detectable SIV levels and after 13 days the virus could only be found in two of them, at very low levels (below 1,000 copies of the virus per millilitre of blood). The researchers repeated the research in eight macaques that were not being treated with ART but this time they found no change in viral load over 13 days.

Dr Adriano Boasso from Imperial College London said: “HIV can have a devastating effect on people’s lives but with advances in Anti-Retroviral Therapy it is becoming a more chronic, manageable disease. Unfortunately, treatment does not work for everyone – some people develop resistance to the drugs and when that happens, we start to run out of options for treating them and delaying the onset of AIDS.

“Our early findings suggest that D-1mT could be used alongside antiretroviral therapy to stop the virus from replicating. The disease can only progress if the virus is replicating, so if we can slow replication down we can reduce the impact of the disease on the patient’s life. We still need to figure out how D-1mT is working, then we can think about developing this as a potential treatment for HIV,” added Dr Boasso.

The results of the new study surprised the researchers because D-1mT did not appear to work in the way they had expected. They had believed it might reactivate the immune system, because D-1mT is able to block an enzyme called IDO, which HIV and SIV use to hold the immune system back. In healthy people, IDO prevents the immune system from attacking the body. HIV and SIV hijack the machinery that makes IDO and use it to stop the immune system from attacking them.

In the new study, the researchers could find no evidence that D-1mT reactivated the immune response against SIV, although they do not exclude this possibility. They are now keen to carry out further research to explore how D-1mT is working.

“The effect D-1mT seemed to have on viral load was really encouraging but it was a surprise to us – we didn’t expect D-1mT to work only in macaques that were already being treated with ART. It seems that D-1mT synergises with ART and we would really like to find out how this works,” said Dr Boasso.

In healthy people, the IDO enzyme controls allergic reactions and autoimmune diseases and it also stops the foetus from being rejected in pregnancy. As D-1mT blocks IDO, the researchers say that its effects may need to be tested in SIV-infected macaques over a longer time, to determine if taking the drug could increase the risk of these conditions.

D-1mT is currently in Phase I clinical trials to test its safety and potential efficacy as a treatment for cancer, which should indicate whether the drug is suitable for treating human patients. The researchers hope that if D-1mT proves safe in the initial trials for cancer and shows further promise for treating HIV, trials for using D-1mT as a treatment for HIV could begin as early as 5 years from now.

J. Immunol., Apr 2009; 182: 4313 – 4320. doi:10.4049/jimmunol.0803314
Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques
Adriano Boasso, Monica Vaccari, Dietmar Fuchs, Andrew W. Hardy, Wen-Po Tsai, Elzbieta Tryniszewska, Gene M. Shearer, and Genoveffa Franchini

Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-D-tryptophan (D-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). D-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, D-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, D-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-β mRNA expression in lymph nodes of ART-treated macaques after D-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by D-1mT, which may account for the lack of effect on plasma Kyn. Finally, D-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, D-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which D-1mT inhibited SIV replication in vivo.

You Wear Me Out: Self-control Is Exhausting

Exerting self-control is exhausting. In fact, using self-control in one situation impairs our ability to use self-control in subsequent, even unrelated, situations. What about thinking of other people exerting self-control?

Earlier research has shown that imagining actions can cause the same reactions as if we were actually performing them (e.g., simulating eating a disgusting food results in a revolting face, even if no food has been eaten) and psychologists Joshua M. Ackerman and John A. Bargh from Yale University, along with Noah J. Goldstein and Jenessa R. Shapiro from the University of California, Los Angeles explored what affect thinking about other people’s self-control has on our own thoughts and behavior.

Participants were presented with a story about a hungry waiter who was surrounded by delicious food, but was not allowed to sample any, for fear of being fired. Half of the participants simply read the story and the other half were told to imagine themselves in the waiter’s shoes. Next, all of the participants were shown images of mid- to high-priced items (e.g., cars and TVs) and were to indicate how much they would pay for them. In a follow-up experiment, some of the participants read the same story and others read a similar story in which the waiter was not hungry and did not have to use self-control. Just as in the first experiment, some of the participants read the story while others imagined themselves as the waiter. All of these volunteers then participated in a word game and a memory task.

The results, reported in Psychological Science reveal that the participants who imagined themselves in the waiter’s position were more willing to spend greater amounts of money on the luxury items – they had exhausted their capacity for self-control and restraint, leading them to spend more money. In the follow-up experiment, the volunteers who read and imagined the story of the waiter who was not hungry performed much better on the word game and memory task. Overall, the group that imagined themselves as the waiter from the original story, who exercised self-control and did not eat any food, performed the worst on the word game and memory tasks.

These findings suggest that our own self-control can be worn out simply by mentally simulating another person acting with self-control. The authors note, for example, that imagining someone else’s self-control “could result in small breakdowns of self-control, such as employees speaking out improperly during a meeting, to catastrophic ones, such as police officers responding to an emotionally charged encounter with deadly force.”

Psychological Science, 2009; 20 (3): 326 DOI: 10.1111/j.1467-9280.2009.02290.x
You Wear Me Out: The Vicarious Depletion of Self-Control.
Joshua M. Ackerman, Noah J. Goldstein, Jenessa R. Shapiro, and John A. Bargh

Address correspondence to Joshua Ackerman, Yale University, Department of Psychology, P.O. Box 208205, New Haven, CT 06520-8205, e-mail: joshua.ackerman@yale.edu.

ABSTRACT—Acts of self-control may deplete an individual’s self-regulatory resources. But what are the consequences of perceiving other people’s use of self-control? Mentally simulating the actions of others has been found to elicit psychological effects consistent with the actual performance of those actions. Here, we consider how simulating versus merely perceiving the use of willpower can affect self-control abilities. In Study 1, participants who simulated the perspective of a person exercising self-control exhibited less restraint over spending on consumer products than did other participants. In Study 2, participants who took the perspective of a person using self-control exerted less willpower on an unrelated lexical generation task than did participants who took the perspective of a person who did not use self-control. Conversely, participants who merely read about another person’s self-control exerted more willpower than did those who read about actions not requiring self-control. These findings suggest that the actions of other people may either deplete or boost one’s own self-control, depending on whether one mentally simulates those actions or merely perceives them.

modern democracy

the inescapable misery of contemporary democracy is rooted in the fact, that its exponents are elected due to their media literacy while it would be their job to solve technical problems of permanently growing complexity. next to the appallling financial power concentrated outside of any democratic control, this casts a light of doubt on the legitimacy of any form of government nowadays.

who said, life was about seized opportunities? that sounds more optimistic than precise. looking at the odds, it appears to be more an affair of missed chances, actually….

Brain Activity Linked While Anticipating Musical Structures

Neuroscientists at Georgetown University Medical Center have, for the first time, shown what brain activity looks like when someone anticipates an action or sensory input which soon follows.

In the February 25 issue of the Journal of Neuroscience, they say this neural clairvoyance involves strong activity in areas of the brain responsible for preparing the body to move.

The findings were made by using functional magnetic resonance imaging (fMRI) in a group of student volunteers who brought with them favorite music CDs. The scientists examined brain images during the silence between songs, and found it brimming with activity. Other students who listened to music they had never heard in sequence before did not have that same neural bustle.

“This now explains how it is that, even before an anticipated song is actually heard, a person can start to tap fingers, dance, or sing to the music they imagine is coming next,” says Josef Rauschecker, PhD, director of the Program in Cognitive and Computational Sciences (PICCS), at Georgetown University Medical Center.

While it makes sense that song sequences can be memorized and thus anticipated by a listener, no one before has ever documented the brain activity that is underway in the silence between songs, he says.

“The brain is all about anticipation and prediction, yet no one has shown what that looks like in terms of neural action,” says Rauschecker.

He adds that this same process, known as cued associative learning, likely occurs whenever a human is expecting any particular action to happen, be it in sports, music, or language.

“It is how a skier is mentally prepared to go down a familiar course during the Olympics, or how a piano player knows to move fingers along the keyboard to hit the next correct key,” Rauschecker says.

This sounds simple, but it isn’t, he says. “It is not trivial to store a temporal sequence in the brain, because the brain doesn’t have any moving parts like a tape recorder or CD player. The whole brain needs to be involved because it has to be ready to execute that sequence. “

In the students who knew the order of songs on their CD, the researchers found that during the anticipatory silence between the songs excitatory signals passed from the prefrontal cortex to the nearby premotor cortex. The prefrontal cortex is the brain’s “executive” center, which plans and orchestrates complex cognitive behaviors. The premotor cortex and its associated systems, which include the basal ganglia and the cerebellum, is involved in preparing the body to act – perhaps to move or to sing.

“These structures are involved in both thinking and acting, and it appears that music patterns are being stored and learned here,” Rauschecker says.

“We hadn’t anticipated that,” he adds with a laugh. “We didn’t know the premotor areas would be involved.”

All animals have some ability to cognitively predict motor activity, he says. “That’s why a bird can sing. But humans are the most associative of animals, which is why we have such a large prefrontal cortex. We have a lot of sequences that we need to store in order to predict what we should do.”
The Journal of Neuroscience, February 25, 2009, 29(8):2477-2485; doi:10.1523/JNEUROSCI.4921-08.2009
Brain Activation during Anticipation of Sound Sequences.
Amber M. Leaver, Jennifer Van Lare, Brandon Zielinski, Andrea R. Halpern, and Josef P. Rauschecker.

Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive “anticipatory imagery” at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in “training” frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains.

Key words: prefrontal cortex; basal ganglia; auditory; fMRI; learning and memory; motor learning

Overdoing It? Simple Techniques Can Help Avoid Overindulgence

Some people overindulge on junk foods or needless shopping sprees when they feel depressed. Others lose control the minute they feel happy. Is there a way to avoid such extreme actions? A new study in the Journal of Consumer Research demonstrates simple techniques that can help people act in their long-term interests rather than indulging in immediate pleasures.

“The recipe is simple,” write authors Aparna A. Labroo (University of Chicago) and Anirban Mukhopadhyay (University of Michigan). “If you are feeling happy, focus on reasons why those feelings will last, and if you are feeling unhappy, focus on reasons why those feelings will pass.”

The authors explain that indulgence is often a result of people trying to improve their mood. People tend to indulge themselves when they believe their happy feelings might pass unless they do something to prolong the good feeling. Others feel miserable and believe they’ll be stuck with the blues unless they do something to improve their mood.

“People strategically manage their actions both to accomplish their long-term interests and to attain immediate pleasures. If they believe they need to take action to regulate their feelings in the here and now, they tend to indulge in immediate pleasures. In contrast, if they believe such actions are not required, they act in their long-term interests,” write the authors.

In one study, the authors presented participants (who were dieters) with line drawings of either smiley or frowny faces. “The results revealed that simply associating a smiley with less transience (coloring with a superfine micro tip, which takes a long time to color, rather than a sharpie, which colors the face in a few short strokes) resulted in people becoming more likely to act their long-term interests and choose an apple as a snack rather than a chocolate,” write the authors.

Next time your misery makes you reach for the hot fudge, take a moment to think about how the feelings will pass. “Simply thinking life is not so bad might actually help you make your life a little better by helping you make a healthy food choice,” the researchers conclude

Journal of Consumer Research, 2009; 0 (0): 090114112928060 DOI: 10.1086/597159

Lay Theories of Emotion Transience and the Search for Happiness: A Fresh Perspective on Affect Regulation.

Aparna A. Labroo and Anirban Mukhopadhyay.

Across six studies, we demonstrate that consumers have beliefs pertaining to the transience of emotion, which, along with their current feelings, determine the extent to which they regulate their immediate affect. If consumers believe that emotion is fleeting, those feeling happy (vs. unhappy) engage in affect regulation because they infer that they need to take actions to maintain their positive feelings. In contrast, if consumers believe that emotion is lasting, those feeling unhappy (vs. happy) engage in affect regulation because they infer that the negative feelings will persist unless they take actions to repair them. These effects are obtained with measured and with manipulated beliefs, and they occur only when the theories pertain specifically to emotion. Implications and areas for future research are discussed.

How We Think Before We Speak: Making Sense Of Sentences

We engage in numerous discussions throughout the day, about a variety of topics, from work assignments to the Super Bowl to what we are having for dinner that evening. We effortlessly move from conversation to conversation, probably not thinking twice about our brain’s ability to understand everything that is being said to us. How does the brain turn seemingly random sounds and letters into sentences with clear meaning?

In a new report in Current Directions in Psychological Science, a journal of the Association for Psychological Science, psychologist Jos J.A. Van Berkum from the Max Planck Institute in The Netherlands describes recent experiments using brain waves to understand how we are able to make sense of sentences.

In these experiments, Van Berkum and his colleagues examined Event Related Potentials (or ERPs) as people read or heard critical sentences as part of a longer text, or placed in some other type of context. ERPs are changes in brain activity that occur when we hear a certain stimulus, such as a tone or a word. Due to their speed, ERPs are useful for detecting the incredibly fast processes involved in understanding language.

Analysis of the ERPs has consistently indicated just how quickly the brain is able to relate unfolding sentences to earlier ones. For example, Van Berkum and colleagues have shown that listeners only need a fraction of a second to determine that a word is out of place, given what the wider story is about. As soon as listeners hear an unexpected word, their brain generates a specific ERP, the N400 effect (so named because it is a negative deflection peaking around 400 milliseconds). And even more interesting, this ERP will usually occur before the word is even finished being spoken.

In addition to the words themselves, the person speaking them is a crucial component in understanding what is being said. Van Berkum also saw an N400 effect occurring very rapidly when the content of a statement being spoken did not match with the voice of the speaker (e.g. “I have a large tattoo on my back” in an upper-class accent or “I like olives” in a young child’s voice). These findings suggest that the brain very quickly classifies someone based on what their voice sounds like and also makes use of social stereotypes to interpret the meaning of what is being said. Van Berkum speculates that “the linguistic brain seems much more ‘messy’ and opportunistic than originally believed, taking any partial cue that seems to bear on interpretation into account as soon as it can.”

But how does the language brain act so fast? Recent findings suggest that, as we read or have a conversation, our brains are continuously trying to predict upcoming information. Van Berkum suggests that this anticipation is a combination of a detailed analysis about what has been said before with taking ‘quick-and-dirty’ shortcuts to figure out what, most likely, the next bit of information will be.

One important element in keeping up with a conversation is knowing what or whom speakers are actually referring to. For example, when we hear the statement, “David praised Linda because. . .,” we expect to find out more about Linda, not David. Van Berkum and colleagues showed that when listeners heard “David praised Linda because he. . .,” there was a very strong ERP effect occurring with the word “he,” of the type that is also elicited by grammatical errors. Although the pronoun is grammatically correct in this statement, the ERP occurred because the brain was just not expecting it. This suggests that the brain will sometimes ignore the rules of grammar when trying to comprehend sentences.

These findings reveal that, as we make sense of an unfolding sentence, our brains very rapidly draw upon a wide range of information, including what was stated previously and who the speaker is, in helping us understand what is being said to us. Sentence understanding is not just about diligently combining stored word meanings. The brain rapidly throws in everything it knows, and it is always looking ahead.

Current Directions in Psychological Science, 2008; 17 (6): 376 DOI: 10.1111/j.1467-8721.2008.00609.x
Understanding Sentences in Context: What Brain Waves Can Tell Us.
Jos J.A. Van Berkum

ABSTRACT—Language comprehension looks pretty easy. You pick up a novel and simply enjoy the plot, or ponder the human condition. You strike a conversation and listen to whatever the other person has to say. Although what you’re taking in is a bunch of letters and sounds, what you really perceive—if all goes well—is meaning. But how do you get from one to the other so easily? The experiments with brain waves (event-related brain potentials or ERPs) reviewed here show that the linguistic brain rapidly draws upon a wide variety of information sources, including prior text and inferences about the speaker. Furthermore, people anticipate what might be said about whom, they use heuristics to arrive at the earliest possible interpretation, and if it makes sense, they sometimes even ignore the grammar. Language comprehension is opportunistic, proactive, and, above all, immediately context-dependent.

The Liberating Effects Of Losing Control

Self-control is one of our most cherished values. We applaud those with the discipline to regulate their appetites and actions, and we try hard to instill this virtue in our children. We celebrate the power of the mind to make hard choices and keep us on course. But is it possible that willpower can sometimes be an obstacle rather than a means to happiness and harmony?

Tufts University psychologists Evan Apfelbaum and Samuel Sommers were intrigued by the notion that too much self-control may indeed have a downside – and that relinquishing some power might be paradoxically tonic, both for individuals and for society.

They explored the virtue of powerlessness in the arena of race relations. They figured that well-intentioned people are careful – sometimes hyper-careful – not to say the wrong thing about race in a mixed-race group. Furthermore, they thought that such effortful self-control might actually cause both unease and guarded behavior, which could in turn be misconstrued as racial prejudice.

To test this, they ran a group of white volunteers through a series of computer-based mental exercises that are so challenging that they temporarily deplete the cognitive reserves needed for discipline. Once they had the volunteers in this compromised state of mind, they put them (and others not so depleted) into a social situation with the potential for racial tension – they met with either a white or black interviewer and discussed racial diversity. Afterward, the volunteers rated the interaction for comfort, awkwardness, and enjoyment. In addition, independent judges – both black and white – analyzed the five-minute interactions, commenting on how cautious the volunteers were, how direct in their answers – and how racially prejudiced.

As reported in Psychological Science, a journal of the Association for Psychological Science, those who were mentally depleted – that is, those lacking discipline and self-control – found talking about race with a black interviewer much more enjoyable than did those with their self-control intact. That’s presumably because they weren’t working so hard at monitoring and curbing what they said. What’s more, independent black observers found that the powerless volunteers were much more direct and authentic in conversation. And perhaps most striking, blacks saw the less inhibited whites as less prejudiced against blacks. In other words, relinquishing power over oneself appears to thwart over-thinking and “liberate” people for more authentic relationships.

Psychological Science Volume 20, Issue 2, Date: February 2009, Pages: 139-143

Liberating Effects of Losing Executive Control

Evan P. Apfelbaum, Samuel R. Sommers

ABSTRACT—Across numerous domains, research has consistently linked decreased capacity for executive control to negative outcomes. Under some conditions, however, this deficit may translate into gains: When individuals’ regulatory strategies are maladaptive, depletion of the resource fueling such strategies may facilitate positive outcomes, both intra- and interpersonally. We tested this prediction in the context of contentious intergroup interaction, a domain characterized by regulatory practices of questionable utility. White participants discussed approaches to campus diversity with a White or Black partner immediately after performing a depleting or control computer task. In intergroup encounters, depleted participants enjoyed the interaction more, exhibited less inhibited behavior, and seemed less prejudiced to Black observers than did control participants—converging evidence of beneficial effects. Although executive capacity typically sustains optimal functioning, these results indicate that, in some cases, it also can obstruct positive outcomes, not to mention the potential for open dialogue regarding divisive social issues.

New ‘Light’ On Fascinating Rhythms Of Circadian Clock

Scientists have long known that interrupting the 24-hour circadian rhythm plays havoc with the lives and health of medical, military and airline personnel, factory employees and travelers.

A new paper by University of Notre Dame biologist Giles Duffield and a team of researchers that appears in this month’s edition of the journal Cell Biology sheds new light on circadian timing systems and focuses on a key gene that seems to regulate the response of the circadian clock to light signals.

“Circadian rhythms are important and exciting because they pervade many aspects of biochemistry, physiology and behavior, either subtly or overtly,” Duffield said. “For example, the human sleep-wake cycle is a very obvious rhythm and tightly gated to the night, while perhaps less obvious is that virtually all hormones oscillate with a 24-hour rhythm and up to 10 percent of genes in each cell are rhythmically controlled.” An estimated 16 percent of the U.S. working population is involved in rotational shift work, and a significant population is affected by jet lag and related sleep-wake disorders. The impact of the large shifts in the body’s internal clock that these individuals experience can be profound, contributing to increased accident rates, medical errors and the development of particular illnesses.

“Both the Three Mile Island disaster in 1979 and the Chernobyl disaster in 1986 occurred late at night or early in the morning,” Duffield said. “Most truck accidents occur around 2 a.m. Incidents of cancer and cardiovascular disease are elevated in trans-Atlantic airline staff and in shift workers.”

The master circadian clock in the human resides within the suprachiasmatic nucleus of the hypothalamic brain and receives direct input from the retina (eye) through which the clock can be reset or synchronized on a daily basis to the prevailing light-dark cycle. This provides both time of day and also time of year information to the brain and body. Things can go wrong with the internal clocks when either the clock system or its light input pathway is disrupted.

Using DNA microarray techniques, Duffield and the other researchers identified an important gene called the “Inhibitor of DNA-binding 2″ (Id2) and found that the gene is rhythmically expressed in various tissues including the suprachiasmatic nucleus.

“In the last few years, my laboratory has focused on a family of transcription factor genes expressed in the suprachiasmatic nucleus, liver and heart,” Duffield said. “In conjunction with colleagues at Dartmouth Medical School and Norris Cotton Cancer Center, we produced a knockout mouse that does not express the Id2 gene and is thus null for the functional Id2 protein. By exposing these mice to a time-zone change in their light-dark cycle, we were able to examine the effect of artificial jet lag. We altered the light-dark conditions for these mice to produce an effect that was the equivalent of a person flying from Athens to Los Angeles, a 10-hour delay of their cycle.

“We discovered that the knockout mice took only one or two days to recover from jet lag, while unaltered mice required four or five days to fully adjust. It’s like we removed the hand brake on their molecular machinery.”

The experimental results have important implications for understanding the development and functioning of the circadian clock in the brain and peripheral tissues such as the liver and heart.

“Eight years ago, researchers realized that even if you destroy the suprachiasmatic nuclei of the hypothalamus or examine peripheral organs in isolation, there are still working clock systems in many other tissues of the body,” Duffield said.

It turns out that many of the cells throughout our bodies have an intrinsic circadian clock mechanism and that jet lag and shift work can produce internal asynchrony between each of our tissue-specific clocks.

Our brains, on a daily basis, generate the hormonal and neuronal signals that influence the cellular clocks in the peripheral tissues. If this communication line is disrupted, the liver, for example, ends up on one time zone, and the brain on another.

These peripheral clocks in the body’s organ systems cannot themselves receive information directly. To know what time of day it is in relation to the external environment, these tissues depend on signals originating in the suprachiasmatic nucleus: every day the brain sends signals that inform the peripheral cells to adjust the phase of their rhythms, like the pin of a wrist watch being moved a little bit forward or backward.

If we could somehow tinker with this system in the adult human, it might be possible to reduce the effects of jet-lag and shift work by rapidly adjusting our internal clock. Duffield and the team of researchers may have uncovered an important target for such remedies by identifying the Id2 gene, which appears to in some way regulate the magnitude of response of the circadian clock to light signals.

Curr Biol. 2009 Feb 11. [Epub ahead of print]

A Role for Id2 in Regulating Photic Entrainment of the Mammalian Circadian System.

Duffield GE, Watson NP, Mantani A, Peirson SN, Robles-Murguia M, Loros JJ, Israel MA, Dunlap JC.

Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2(-/-) mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4(-/-) mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

When Dreaming Affects People’s Judgment

While science tries to understand the stuff dreams are made of, humans, from cultures all over the world, continue to believe that dreams contain important hidden truths, according to newly published research.

In six different studies, researchers surveyed nearly 1,100 people about their dreams. “Psychologists’ interpretations of the meaning of dreams vary widely,” said Carey Morewedge, an assistant professor at Carnegie Mellon University and the study’s lead author. “But our research shows that people believe their dreams provide meaningful insight into themselves and their world.”

In one study that surveyed general beliefs about dreams, Morewedge and co-author Michael Norton, an assistant professor at Harvard Business School, surveyed 149 university students in the United States, India and South Korea. The researchers asked the students to rate different theories about dreams. Across all three cultures, an overwhelming majority of the students endorsed the theory that dreams reveal hidden truths about themselves and the world, a belief also endorsed by a nationally representative sample of Americans.

In another study reported in the article, the researchers wanted to explore how dreams might influence people’s waking behavior. They surveyed 182 commuters at a Boston train station, asking them to imagine that one of four possible scenarios had happened the night before a scheduled airline trip: The national threat level was raised to orange, indicating a high risk of terrorist attack; they consciously thought about their plane crashing; they dreamed about a plane crash; or a real plane crash occurred on the route they planned to take. A dream of a plane crash was more likely to affect travel plans than either thinking about a crash or a government warning, and the dream of a plane crash produced a similar level of anxiety as did an actual crash.

Finally, the researchers wanted to find out whether people perceive all dreams as equally meaningful, or whether their interpretations were influenced by their waking beliefs and desires. In another study, 270 men and women from across the United States took a short online survey in which they were asked to remember a dream they had had about a person they knew. People ascribed more importance to pleasant dreams about a person they liked as compared to a person they did not like, while they were more likely to consider an unpleasant dream more meaningful if it was about a person they disliked.

“In other words,” said Morewedge, “people attribute meaning to dreams when it corresponds with their pre-existing beliefs and desires. This was also the case in another experiment which demonstrated that people who believe in God were likely to consider any dream in which God spoke to them to be meaningful; agnostics, however, considered dreams in which God spoke to be more meaningful when God commanded them to take a pleasant vacation than when God commanded them to engage in self-sacrifice.”

The authors say more research is needed to explore fully how people interpret their dreams, and in what cases dreams may actually reveal hidden information.. “Most people understand that dreams are unlikely to predict the future but that doesn’t prevent them from finding meaning in their dreams, whether their contents are mundane or bizarre,” said Morewedge.

Journal of Personality and Social Psychology. Vol 96(2), Feb 2009, 249-264. DOI: 10.1037/a0013264
When dreaming is believing: The (motivated) interpretation of dreams.

This research investigated laypeople’s interpretation of their dreams. Participants from both Eastern and Western cultures believed that dreams contain hidden truths (Study 1) and considered dreams to provide more meaningful information about the world than similar waking thoughts (Studies 2 and 3). The meaningfulness attributed to specific dreams, however, was moderated by the extent to which the content of those dreams accorded with participants’ preexisting beliefs–from the theories they endorsed to attitudes toward acquaintances, relationships with friends, and faith in God (Studies 3-6). Finally, dream content influenced judgment: Participants reported greater affection for a friend after considering a dream in which a friend protected rather than betrayed them (Study 5) and were equally reluctant to fly after dreaming or learning of a plane crash (Studies 2 and 3). Together, these results suggest that people engage in motivated interpretation of their dreams and that these interpretations impact their everyday lives. (PsycINFO Database Record (c) 2009 APA, all rights reserved)