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Primates’ Social Intelligence Overestimated?

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… at least that of humans sometimes is.

Leaving the joke aside, grooming behaviour displayed by primates is due to less rational behaviour than often thought. According to a computer model developed by scientists at the University of Groningen, one basic rule explains all possible grooming patterns: individuals will groom others if they’re afraid they’ll lose from them in a fight.

social grooming

Primates are assumed to reconcile their conflicts by grooming each other after a fight. They are also supposed to carry out intricate trading of grooming for the receipt of help in fights. Professor and theoretical biologist Charlotte Hemelrijk shows in a computer simulation that many patterns of reconciliation and exchange surprisingly emerge simply from fear of losing a fight with another individual. ‘This shows that reconciliation and exchange behaviour are not necessarily conscious behaviour’, Hemelrijk — specialist in self-organization in social systems — states. ‘It’s simply a consequence of rank and of which primates are in the vicinity of the primate that wants to groom.’ The results of the research conducted by the group that worked with Hemelrijk on the computer model have appeared in late December in the journal PloS Computational Biology.

Intelligence

‘Primates are intelligent, but their intelligence is overestimated. The social behaviour of primates is explained on the basis of cognitive considerations by primates that are too sophisticated’, Hemelrijk continues. ‘Primates are assumed to use their intelligence continually and to be very calculating. They’re supposed to reconcile fights and to do so preferably with partners that could mean a lot to them.’ This would explain why primates prefer grooming partners higher in rank in order to gain more effective support in fights. Moral considerations would bring them to repay the grooming costs by grooming others.

Such behaviour patterns all presuppose a rational thought process, according to Hemelrijk: ‘In order to reconcile, the primates must recall exactly which fight they last had and with whom. They must also be able to gauge the importance of each relationship. And for the reciprocity and repayment, they must keep careful track how often and from whom they have received which grooming or support ‘service’ in order to be able to repay it sufficiently.’

GrooFiWorld

However, all these suppositions are unnecessary according to Hemelrijk: ‘Our computer model GrooFiWorld shows that complex calculating behaviour is completely unnecessary. We can add the simple rule to the existing DomWorld model that an individual will begin grooming another when it expects to lose from it upon attacking the other. This in itself leads to many of the complex patterns of friendly behaviour observed in real primates.’ In the DomWorld model, individuals group together and compete with their neighbours.

With the help of the computer model, Hemelrijk shows that most friendship patterns are due to the proximity of other animals. In turn, the proximity is the result of dominance interactions. The fear of losing a fight also plays an important role. ‘Apparent reconciliation behaviour is the result of individuals being nearer their opponent after a fight than otherwise’, the professor explains. Repaying grooming that has been received is the result of some individuals being nearer to certain others more often. Since they groom nearby primates in particular, any grooming received will automatically be repaid.’

The model and reality

That this is shown by the computer model does not mean that primates are not capable of displaying intelligent social behaviour, according to Hemelrijk. ‘The resemblance of patterns of friendly behaviour in our model to those in reality means that more evidence is needed to be able to draw the conclusion that friendly relationships are based on human, calculating considerations. Our model is a ‘null model’ providing simple explanations which are especially useful for further research into friendly behaviour in primates, in particular into that of macaques.’

Such computer models are not only useful in analyzing primate behaviour, but also to gain insight into the social behaviour of all sorts of species that live in groups. It could for instance provide ideas for further research into the flocking behaviour of starlings. Hemelrijk: ‘Simulations thus are also very important for researchers working out in the field. They can research the connection between models and reality.’

PLoS Computational Biology, 2009; 5 (12): e1000630 DOI: doi:10.1371/journal.pcbi.1000630
Emergent Patterns of Social Affiliation in Primates, a Model.
Ivan Puga-Gonzalez, Hanno Hildenbrandt, Charlotte K. Hemelrijk

Abstract Many patterns of affiliative behaviour have been described for primates, for instance: reciprocation and exchange of grooming, grooming others of similar rank, reconciliation of fights, and preferential reconciliation with more valuable partners. For these patterns several functions and underlying cognitive processes have been suggested. It is, however, difficult to imagine how animals may combine these diverse considerations in their mind. Although the co-variation hypothesis, by limiting the social possibilities an individual has, constrains the number of cognitive considerations an individual has to take, it does not present an integrated theory of affiliative patterns either. In the present paper, after surveying patterns of affiliation in egalitarian and despotic macaques, we use an individual-based model with a high potential for self-organisation as a starting point for such an integrative approach. In our model, called GrooFiWorld, individuals group and, upon meeting each other, may perform a dominance interaction of which the outcomes of winning and losing are self-reinforcing. Besides, if individuals think they will be defeated, they consider grooming others. Here, the greater their anxiety is, the greater their “motivation” to groom others. Our model generates patterns similar to many affiliative patterns of empirical data. By merely increasing the intensity of aggression, affiliative patterns in the model change from those resembling egalitarian macaques to those resembling despotic ones. Our model produces such patterns without assuming in the mind of the individual the specific cognitive processes that are usually thought to underlie these patterns (such as recordkeeping of the acts given and received, a tendency to exchange, memory of the former fight, selective attraction to the former opponent, and estimation of the value of a relationship). Our model can be used as a null model to increase our understanding of affiliative behaviour among primates, in particular macaques.

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Written by huehueteotl

January 11, 2010 at 10:41 pm

Over The Edge: But Not Without Warning Signals Of Change

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What do abrupt changes in ocean circulation and Earth’s climate, shifts in wildlife populations and ecosystems, the global finance market and its system-wide crashes, and asthma attacks and epileptic seizures have in common?

According to a paper published this week in the journal Nature, all share generic early-warning signals that indicate a critical threshold of change dead ahead.

In the paper, Martin Scheffer of Wageningen University in The Netherlands and co-authors, including William Brock and Stephen Carpenter of the University of Wisconsin at Madison and George Sugihara of the Scripps Institution of Oceanography in La Jolla, Calif., found that similar symptoms occur in many systems as they approach a critical state of transition.

“It’s increasingly clear that many complex systems have critical thresholds — ‘tipping points’ — at which these systems shift abruptly from one state to another,” write the scientists in their paper.

Especially relevant, they discovered, is that “catastrophic bifurcations,” a diverging of the ways, propel a system toward a new state once a certain threshold is exceeded.

Like Robert Frost’s well-known poem about two paths diverging in a wood, a system follows a trail for so long, then often comes to a switchpoint at which it will strike out in a completely new direction.

That system may be as tiny as the alveoli in human lungs or as large as global climate.

“These are compelling insights into the transitions in human and natural systems,” says Henry Gholz, program director in the National Science Foundation (NSF)’s Division of Environmental Biology, which supported the research along with NSF’s Division of Ocean Sciences.

“The information comes at a critical time — a time when Earth’s and, our fragility, have been highlighted by global financial collapses, debates over health care reform, and concern about rapid change in climate and ecological systems.”

It all comes down to what scientists call “squealing,” or “variance amplification near critical points,” when a system moves back and forth between two states.

“A system may shift permanently to an altered state if an underlying slow change in conditions persists, moving it to a new situation,” says Carpenter.

Eutrophication in lakes, shifts in climate, and epileptic seizures all are preceded by squealing.

Squealing, for example, announced the impending abrupt end of Earth’s Younger Dryas cold period some 12,000 years ago, the scientists believe. The later part of this episode alternated between a cold mode and a warm mode. The Younger Dryas eventually ended in a sharp shift to the relatively warm and stable conditions of the Holocene epoch.

The increasing climate variability of recent times, state the paper’s authors, may be interpreted as a signal that the near-term future could bring a transition from glacial and interglacial oscillations to a new state — one with permanent Northern Hemisphere glaciation in Earth’s mid-latitudes.

In ecology, stable states separated by critical thresholds of change occur in ecosystems from rangelands to oceans, says Carpenter.

The way in which plants stop growing during a drought is an example. At a certain point, fields become deserts, and no amount of rain will bring vegetation back to life. Before this transition, plant life peters out, disappearing in patches until nothing but dry-as-bones land is left.

Early-warning signals are also found in exploited fish stocks. Harvesting leads to increased fluctuations in fish populations. Fish are eventually driven toward a transition to a cyclic or chaotic state.

Humans aren’t exempt from abrupt transitions. Epileptic seizures and asthma attacks are cases in point. Our lungs can show a pattern of bronchoconstriction that may be the prelude to dangerous respiratory failure, and which resembles the pattern of collapsing land vegetation during a drought.

Epileptic seizures happen when neighboring neural cells all start firing in synchrony. Minutes before a seizure, a certain variance occurs in the electrical signals recorded in an EEG.

Shifts in financial markets also have early warnings. Stock market events are heralded by increased trading volatility. Correlation among returns to stocks in a falling market and patterns in options prices may serve as early-warning indicators.

“In systems in which we can observe transitions repeatedly,” write the scientists, “such as lakes, ranges or fields, and such as human physiology, we may discover where the thresholds are.

“If we have reason to suspect the possibility of a critical transition, early-warning signals may be a significant step forward in judging whether the probability of an event is increasing.”
Nature 461, 53-59 (3 September 2009) | doi:10.1038/nature08227
Early-warning signals for critical transitions

Marten Scheffer, Jordi Bascompte, William A. Brock, Victor Brovkin5, Stephen R. Carpenter, Vasilis Dakos1, Hermann Held, Egbert H. van Nes, Max Rietkerk & George Sugihara

Abstract: Complex dynamical systems, ranging from ecosystems to financial markets and the climate, can have tipping points at which a sudden shift to a contrasting dynamical regime may occur. Although predicting such critical points before they are reached is extremely difficult, work in different scientific fields is now suggesting the existence of generic early-warning signals that may indicate for a wide class of systems if a critical threshold is approaching.

Written by huehueteotl

September 7, 2009 at 7:46 am

New ‘Light’ On Fascinating Rhythms Of Circadian Clock

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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.

Written by huehueteotl

February 20, 2009 at 8:54 am

Care To Try The ‘Beauty Machine’?

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Beauty is in the eye of the beholder. This saying first appeared in the 3rd century BC in Greek. It didn’t appear in its current form in print until the 19th century, but in the meantime there were various written forms that expressed much the same thought. In 1588, the English dramatist John Lyly, in his Euphues and his England, wrote:

“…as neere is Fancie to Beautie, as the pricke to the Rose, as the stalke to the rynde, as the earth to the roote.”

Shakespeare expressed a similar sentiment in Love’s Labours Lost, 1588:

Good Lord Boyet, my beauty, though but mean,
Needs not the painted flourish of your praise:
Beauty is bought by judgement of the eye,
Not utter’d by base sale of chapmen’s tongues

Benjamin Franklin, in Poor Richard’s Almanack, 1741, wrote:

Beauty, like supreme dominion
Is but supported by opinion

beauty is in the eye of the beholderDavid Hume’s Essays, Moral and Political, 1742, include:

“Beauty in things exists merely in the mind which contemplates them.”

The person who is widely credited with coining the saying in its current form is Margaret Wolfe Hungerford (née Hamilton), who wrote many books, often under the pseudonym of ‘The Duchess’. In Molly Bawn, 1878, there’s the line “Beauty is in the eye of the beholder”, which is the earliest citation of it that I can find in print.

But researchers from Tel Aviv University are now challenging the adage.

They’ve built a beauty machine that, with the press of a button, turns a picture of your own ordinary face into that of a cover model. While its output is currently limited to digitized images, the software may be able to guide plastic surgeons, aid magazine cover editors, and even become a feature incorporated into all digital cameras.

“Beauty, contrary to what most people think, is not simply in the eye of the beholder,” says lead researcher Prof. Daniel Cohen-Or of the Blavatnik School of Computer Sciences at Tel Aviv University. With the aid of computers, attractiveness can be objectified and boiled down to a function of mathematical distances or ratios, he says. This function is the basis for his beauty machine.

In the Eyes of a Majority of Beholders

The research has attracted interest and controversy. Beauty is, after all, a quality that has captivated artists since time immemorial, and its definition has eluded even the world’s greatest philosophers. Prof. Cohen-Or sees things more scientifically.

“Beauty can be quantified by mathematical measurements and ratios. It can be defined as average distances between features, which a majority of people agree are the most beautiful,” says Prof. Cohen-Or. “I don’t claim to know much about beauty. For us, every picture in this research project is just a collection of numbers.”

In his study, published recently in the proceedings of Siggraph, an annual computer graphics conference, Prof. Cohen-Or and his graduate student Tommer Leyvand together with two colleagues surveyed 68 Israeli and German men and women, aged 25 to 40, asking them to rank the beauty of 93 different men’s and women’s faces on a scale of 1 to 7. These scores were then entered into a database and correlated to 250 different measurements and facial features, such as ratios of the nose, chin and distance from ears to eyes. From this, the scientists created an algorithm that applies desirable elements of attractiveness to a fresh image.

True to the Real You

Unlike heavily processed Photoshop images that can make magazine cover models and celebrities unrecognizable, Tel Aviv University’s “beautification engine” is much more subtle. Observers say that the final image it produces retains an unmistakable similarity to the original picture.

Well — in most cases. There is one circumstance where Prof. Cohen-Or’s beauty machine doesn’t work like a charm: when a celebrity’s face is changed.

“We’ve run the faces of people like Brigitte Bardot and Woody Allen through the machine and most people are very unhappy with the results,” he admits. “But in unfamiliar faces, most would agree the output is better.” Prof. Cohen-Or now plans on developing the beauty machine further — to add the third dimension of depth.

ACM SIGGRAPH 2008
Data-Driven Enhancement of Facial Attractiveness
Tommer Leyvand, Daniel Cohen-Or, Gideon Dror and Dani Lischinski

Abstract:
When human raters are presented with a collection of shapes and asked to rank them according to their aesthetic appeal, the results
often indicate that there is a statistical consensus among the raters. Yet it might be difficult to define a succinct set of rules that capture the aesthetic preferences of the raters. In this work, we explore a data-driven approach to aesthetic enhancement of such shapes. Specifically, we focus on the challenging problem of enhancing the aesthetic appeal (or the attractiveness) of human faces in frontal photographs (portraits), while maintaining close similarity with the original.

The key component in our approach is an automatic facial attractiveness engine trained on datasets of faces with accompanying facial attractiveness ratings collected from groups of human raters. Given a new face, we extract a set of distances between a variety of facial feature locations, which define a point in a high-dimensional “face space”. We then search the face space for a nearby point with a higher predicted attractiveness rating. Once such a point is found, the corresponding facial distances are embedded in the plane and serve as a target to define a 2D warp field which maps the original facial features to their adjusted locations. The effectiveness of our technique was experimentally validated by independent rating experiments, which indicate that it is indeed capable of increasing the facial attractiveness of most portraits that we have experimented with.

Written by huehueteotl

November 8, 2008 at 2:10 pm

How The Immune System And Brain Communicate To Control Disease

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In a major step in understanding how the nervous system and the immune system interact, scientists at The Feinstein Institute for Medical Research have identified a new anatomical path through which the brain and the spleen communicate.

The spleen, once thought to be an unnecessary bit of tissue, is now regarded as an organ where important information from the nervous reaches the immune system. Understanding this process could ultimately lead to treatments that target the spleen to send the right message when fighting human disease.

Mauricio Rosas-Ballina, MD, working with colleagues in the laboratory of Kevin J. Tracey, MD, figured out that macrophages in the spleen were making tumor necrosis factor, a powerful inflammation-producing molecule. When they stimulated the vagus nerve, a long nerve that goes from the base of the brain into thoracic and abdominal organs, tumor necrosis factor (TNF) production in the spleen decreased. This study complements previous research performed in Dr. Tracey’s laboratory, which showed that stimulation of the vagus nerve increases survival in laboratory models of sepsis.

The findings were published July 22 in the Proceedings of the National Academy of Sciences. Many laboratories at The Feinstein Institute study the immune system in health and in disease. Every year, about 500,000 people develop severe sepsis, a syndrome triggered when the body’s immune system wages an attack on the body that is well beyond its normal response to an invader. Sepsis kills about 225,000 deaths in the United States each year.

A hundred years ago, the spleen (located in the upper quadrant of the abdomen) was thought to be only reservoir for blood. It has only been in recent years that scientists discovered that the spleen is a manufacturing plant for immune cells, and a site where immune cells and nerves interact. The spleen defends the body against infection, particularly encapsulated bacteria that circulate through the blood.

The hope is to modulate other immune functions like antibody production through the spleen (via vagus nerve stimulation) as a way to modify the course of infections and possibly some autoimmune disorders.

Dr. Rosas-Ballina began following the winding path of the vagus nerve to establish the route it follows to reach the spleen. He was trying, without much luck, to find fibers of the vagus nerve in this organ. And then he went a little further south to the splenic nerve, the nerve that innervates the spleen. Their results indicate that the vagus nerve inherently communicates with the splenic nerve to suppress TNF production by macrophages in the spleen.

According to the prevailing paradigm, the autonomic nervous system is anatomically and functionally divided in sympathetic and parasympathetic branches, which act in opposition to regulate organ function. “The division between the parasympathetic and sympathetic nervous systems is not clear cut,” said Dr. Rosas-Ballina, explaining that the vagus nerve (the major parasympathetic nerve) acts through the splenic nerve to modulate immune function. He said that results of this study suggest that there may be two separate ways the brain communicates with the spleen to regulate immune function. This points the way to a possible solution for treating sepsis. It may be more effective to take advantage of the central nervous system to control cells of the spleen. This way, “you know where the treatment is going,” said Dr. Rosas-Ballina.

Brain Behav Immun. 2008 Jun 27. [Epub ahead of print]
Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway.
Pavlov VA, Parrish WR, Rosas-Ballina M, Ochani M, Puerta M, Ochani K, Chavan S, Al-Abed Y, Tracey KJ.

Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.

The excessive release of cytokines by the immune system contributes importantly to the pathogenesis of inflammatory diseases. Recent advances in understanding the biology of cytokine toxicity led to the discovery of the “cholinergic anti-inflammatory pathway,” defined as neural signals transmitted via the vagus nerve that inhibit cytokine release through a mechanism that requires the alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR). Vagus nerve regulation of peripheral functions is controlled by brain nuclei and neural networks, but despite considerable importance, little is known about the molecular basis for central regulation of the vagus nerve-based cholinergic anti-inflammatory pathway. Here we report that brain acetylcholinesterase activity controls systemic and organ specific TNF production during endotoxemia. Peripheral administration of the acetylcholinesterase inhibitor galantamine significantly reduced serum TNF levels through vagus nerve signaling, and protected against lethality during murine endotoxemia. Administration of a centrally-acting muscarinic receptor antagonist abolished the suppression of TNF by galantamine, indicating that suppressing acetylcholinesterase activity, coupled with central muscarinic receptors, controls peripheral cytokine responses. Administration of galantamine to alpha7nAChR knockout mice failed to suppress TNF levels, indicating that the alpha7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of galantamine. These findings show that inhibition of brain acetylcholinesterase suppresses systemic inflammation through a central muscarinic receptor-mediated and vagal- and alpha7nAChR-dependent mechanism. Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage.

Written by huehueteotl

July 23, 2008 at 7:57 am

How Smoking Encourages Infection

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Smokers are often more prone to bacterial infections and inflammatory diseases than the rest of us, thanks to hundreds of toxic components in their cigarettes. Next to dry and irritated mucosal linings in mouth and respiratory system due to smoke and nicotine, now new research shows that nicotine affects neutrophils, the short-lived white blood cells that defend against infection, by reducing their ability to seek and destroy bacteria.

https://i1.wp.com/www.funpic.hu/files/pics/00026/00026896.jpg

Neutrophils are generated by our bone marrow, which they leave as terminally differentiated cells. Although nicotine is known to affect neutrophils, there has been no study until now of the mechanisms at work when nicotine is present during neutrophil differentiation. David Scott from the Oral Health and Systemic Disease Research Group at the University of Louisville School of Dentistry, Kentucky, USA, along with a team of international colleagues decided to investigate how nicotine influenced the differentiation process.

The authors suggest the processes they observed as contributing to impaired neutrophil function partially explain chronic tobacco users’ increased susceptibility to bacterial infection and inflammatory diseases. A better understanding of this relationship could pave the way for specific therapeutic strategies to treat a number of important tobacco-associated inflammatory diseases and conditions.

The team modeled the neutrophil differentiation process beginning with promyelocytic HL-60 cells, which differentiated into neutrophils following dimethylsulfoxide (DMSO) treatment both with and without nicotine. The researchers found that nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone, but did not affect other neutrophil differentiation markers that they examined.

However, the nicotine treated neutrophils were less able to seek and destroy bacteria than nicotine-free neutrophils. The nicotine suppressed the oxidative burst in HL-60 cells, a function that helps kill invading bacteria. Nicotine also increased MMP-9 release, a factor involved in tissue degradation.

BMC Cell Biol. 2008 Apr 15;9(1):19 [Epub ahead of print]
The influence of nicotine on granulocytic differentiation – inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release.

ABSTRACT: BACKGROUND: Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined. Results: Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be alpha-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05). Conclusions: These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.

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April 18, 2008 at 8:56 am

Hepatitis C: Identification Of A Protein That Inhibits The Virus

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Scientists in the Laboratoire Hépatite C of the Institut de Biologie de Lille in collaboration with INSERM Unit 602 and a laboratory at Stanford University have provided evidence of a protein, called EWI-2wint, that inhibits the hepatitis C virus at an early stage of its infective cycle. This research suggests possible new perspectives for the development of therapies to block the virus before it enters a cell.
The EWI-2wint protein is not present in hepatocytes (liver cells). When it comes into contact with the hepatocyte, the hepatitis C virus can thus bind to the CD81 protein, which will allow it to enter the cell and pursue its infective cycle. In other types of cells in the body, the EWI-2wint protein is present and interacts with CD81, thus preventing the hepatitis C virus from entering these cells. (Credit: Copyright CNRS 2008 Sophana Ung)

Hepatitis C is a major public health problem that affects some 130 million people throughout the world. In France , where there are about 5000 new cases each year, it is estimated that half a million people could be affected by this disease. The causal agent is the hepatitis C virus (HCV) which targets cells in the liver called hepatocytes. HCV infection is usually chronic (60% to 80% of cases) and in the long term can lead to the development of cirrhosis and liver cancer.

Unlike the hepatitis A and B viruses, there is no vaccine to combat this virus. Furthermore, the treatments employed are only of limited efficacy (the failure rate reaches around 40%), and they involve considerable side effects. It is therefore crucial to develop new antiviral compounds to control this infection.

HCV uses at least three receptors to enter and infect a hepatocyte. One of these receptors is the CD81 protein, which has the particular characteristic of associating with numerous other proteins. It was by studying these CD81 partner proteins that the researchers identified the EWI-2wint protein, which prevents the recognition of CD81 by the hepatitis C virus and inhibits it at a very early stage in its infective cycle. This protein is present in other types of cells, which could explain why they are not infected by HCV. Discovery of the role of EWI-2wint in hepatocytes has demonstrated the complexity of the mechanisms of entry of HCV into its target cells, and opens the way to new therapeutic approaches.

PLoS ONE. 2008 Apr 2;3(4):e1866.
The CD81 partner EWI-2wint inhibits hepatitis C virus entry.

Institut de Biologie de Lille (UMR8161), CNRS, Universités de Lille I et Lille II, Institut Pasteur de Lille, Lille, France.

Two to three percent of the world’s population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor.

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April 17, 2008 at 8:45 am