How Bacteria Build Homes Inside Healthy Cells

Bacteria are able to build camouflaged homes for themselves inside healthy cells -- and cause disease -- by manipulating a natural cellular process. 

Purdue University biologists led a team that revealed how a pair of proteins from the bacteria Legionella pneumophila, which causes Legionnaires disease, alters a host protein in order to divert raw materials within the cell for use in building and disguising a large structure that houses the bacteria as it replicates. 

Zhao-Qing Luo, the associate professor of biological sciences who headed the study, said the modification of the host protein creates a dam, blocking proteins that would be used as bricks in cellular construction from reaching their destination. The protein "bricks" are then diverted and incorporated into a bacterial structure called a vacuole that houses bacteria as it replicates within the cell. Because the vacuole contains materials natural to the cell, it goes unrecognized as a foreign structure. 

"The bacterial proteins use the cellular membrane proteins to build their house, which is sort of like a balloon," Luo said. "It needs to stretch and grow bigger as more bacterial replication occurs. The membrane material helps the vacuole be more rubbery and stretchy, and it also camouflages the structure. The bacteria is stealing material from the cell to build their own house and then disguising it so it blends in with the neighborhood." 

The method by which the bacteria achieve this theft is what was most surprising to Luo. 

The bacterial proteins, named AnkX and Lem3, modify the host protein through a biochemical process called phosphorylcholination that is used by healthy cells to regulate immune response. Phosphorylcholination is known to happen in many organisms and involves adding a small chemical group, called the phosphorylcholine moiety, to a target molecule, he said. 

The team discovered that AnkX adds the phosphorylcholine moiety to a host protein involved in moving proteins from the cell's endoplasmic reticulum to their cellular destinations. The modification effectively shuts down this process and creates a dam that blocks the proteins from reaching their destination. 

The bacterial protein Lem3 is positioned outside the vacuole and reverses the modification of the host protein to ensure that the protein "bricks" are free to be used in creation of the bacterial structure. 

This study was the first to identify proteins that directly add and remove the phosphorylcholine moiety, Luo said. 

"We were surprised to find that the bacterial proteins use the phosphorylcholination process and to discover that this process is reversible," he said. "This is evidence of a new way signals are relayed within cells, and we are eager to investigate it." 

The team also found that the phosphorylcholination reaction is carried out at a specific site on the protein called the Fic domain. Previous studies had shown this site induced a different reaction called AMPylation. 

It is rare for a domain to catalyze more than one reaction, and it was thought this site's only responsibility was to transfer the chemical group necessary for AMPylation, Luo said. 

"Revealing that this domain has dual roles is very important to identify or screen for compounds to inhibit its activity and fight disease," he said. "This domain has a much broader involvement in biochemical reactions than we thought and may be a promising target for effective treatments." 

During infection bacteria deliver hundreds of proteins into healthy cells that alter cellular processes to turn the hostile environment into one hospitable to bacterial replication, but the specific roles of only about 20 proteins are known, Luo said. 

"In order to pinpoint proteins that would be good targets for new antibiotics, we need to determine their roles and importance to the success of infection," he said. "We need to understand at the biochemical level exactly what these proteins do and how they take over natural cellular processes. Then we can work on finding ways to block these activities, stop the infection and save lives." 

A paper detailing their National Institutes of Health-funded work is published in the current issue of the Proceedings of National Academy of Sciences. In addition to Luo, Purdue graduate student Yunhao Tan and Randy Ronald of Indiana University co-authored the paper. 

Luo next plans to use the bacterial proteins as a tool to learn more about the complex cellular processes controlled by phosphorylcholination and to determine the biochemical processes role in cell signaling. 

Source: Purdue University [December 20, 2011]

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Brain size may predict risk for early Alzheimer's disease

New research suggests that, in people who don't currently have memory problems, those with smaller regions of the brain's cortex may be more likely to develop symptoms consistent with very early Alzheimer's disease. The study is published in the December 21, 2011, online issue of Neurology®, the medical journal of the American Academy of Neurology. 

"The ability to identify people who are not showing memory problems and other symptoms but may be at a higher risk for cognitive decline is a very important step toward developing new ways for doctors to detect Alzheimer's disease," said Susan Resnick, PhD, with the National Institute on Aging in Baltimore, who wrote an accompanying editorial. 

For the study, researchers used brain scans to measure the thickness of regions of the brain's cortex in 159 people free of dementia with an average age of 76. The brain regions were chosen based on prior studies showing that they shrink in patients with Alzheimer's dementia. Of the 159 people, 19 were classified as at high risk for having early Alzheimer's disease due to smaller size of particular regions known to be vulnerable to Alzheimer's in the brain's cortex, 116 were classified as average risk and 24 as low risk. At the beginning of the study and over the next three years, participants were also given tests that measured memory, problem solving and ability to plan and pay attention. 

The study found that 21 percent of those at high risk experienced cognitive decline during three years of follow-up after the MRI scan, compared to seven percent of those at average risk and none of those at low risk. 

"Further research is needed on how using MRI scans to measure the size of different brain regions in combination with other tests may help identify people at the greatest risk of developing early Alzheimer's as early as possible," said study author Bradford Dickerson, MD, of Massachusetts General Hospital in Boston and a member of the American Academy of Neurology. 

The study also found 60 percent of the group considered most at risk for early Alzheimer's disease had abnormal levels of proteins associated with the disease in cerebrospinal fluid, which is another marker for the disease, compared to 36 percent of those at average risk and 19 percent of those at low risk. 

Source: American Academy of Neurology [December 21, 2011]

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One trait has huge impact on whether alcohol makes you aggressive

Drinking enough alcohol to become intoxicated increases aggression significantly in people who have one particular personality trait, according to new research. But people without that trait don't get any more aggressive when drunk than they would when they're sober. That trait is the ability to consider the future consequences of current actions. 

"People who focus on the here and now, without thinking about the impact on the future, are more aggressive than others when they are sober, but the effect is magnified greatly when they're drunk," said Brad Bushman, lead author of the study and professor of communication and psychology at Ohio State University. 

"If you carefully consider the consequences of your actions, it is unlikely getting drunk is going to make you any more aggressive than you usually are." 

Peter Giancola, professor of psychology, at the University of Kentucky, co-authored the paper with Bushman and led the experiments used in the study. Other co-authors were Dominic Parrott, associate professor of psychology at of Georgia State University and Robert Roth, associate professor of psychiatry, at Dartmouth Medical School. Their results appear online in the Journal of Experimental Social Psychology and will be published in a future print edition. 

Bushman said it makes sense that alcohol would make present-focused people more aggressive. 

"Alcohol has a myopic effect -- it narrows your attention to what is important to you right now. That may be dangerous to someone who already has that tendency to ignore the future consequences of their actions and who is placed in a hostile situation." 

The study involved 495 adults, with an average age of 23, who were social drinkers. Before participating, the participants were screened for any past or present drug, alcohol and psychiatric-related problems. Women were tested to ensure they weren't pregnant. 

All participants completed the "Consideration of Future Consequences scale." They indicated how much they agreed with statements like "I only act to satisfy immediate concerns, figuring the future will take care of itself." Scores on this measure determined how much participants were present-focused or future-focused. 

Half the participants were put in the alcohol group, where they received alcohol mixed with orange juice at a 1:5 ratio. The other half were given orange juice with just a tiny bit of alcohol. The rims of the glasses were also sprayed with alcohol so that they thought they were consuming a full alcoholic beverage. 

Participants in the alcohol group had a mean blood alcohol level of 0.095 just before aggression was measured and 0.105 following, meaning they were legally drunk and that their alcohol levels were rising during the measurement of their aggressive behavior. 

Those in the placebo group had mean blood alcohol levels that didn't exceed 0.015, meaning they had very little alcohol in their systems and were well below standards of intoxication. 

The aggression measure used in this study was developed in 1967 to test aggressiveness through the use of harmless but somewhat painful electric shocks. The researchers measured the participants' threshold to the electric shock pain before the experiment began to ensure that no one received a shock that exceeded what they could take. 

Each of the participants was told that he or she was competing with a same-sex opponent in a computer-based speed reaction test, with the winner delivering an electrical shock to the loser. The winner determined the intensity and the length of the shock delivered to the loser. 

In actuality, there was no opponent. There were 34 trials, and the participant "won" half of them (randomly determined). Each time they "lost," the participants received electric shocks that increased in length and intensity over the course of the trials, and the researchers measured if they retaliated in kind. 

"The participants were led to believe they were dealing with a real jerk who got more and more nasty as the experiment continued," Bushman said. "We tried to mimic what happens in real life, in that the aggression escalated as time went on." 

Results were clear, Bushman said. 

"The less people thought about the future, the more likely they were to retaliate, but especially when they were drunk. People who were present-focused and drunk shocked their opponents longer and harder than anyone else in the study," he said. 

"Alcohol didn't have much effect on the aggressiveness of people who were future-focused." 

Men were more aggressive than women overall, but the effects of alcohol and personality were similar in both sexes. In other words, women who were present-focused were still much more aggressive when drunk than were women who were future-focused, just like men. 

Bushman said the results should serve as a warning to people who live only in the moment without thinking too much about the future. 

"If you're that kind of person, you really should watch your drinking. Combining alcohol with a focus on the present can be a recipe for disaster." 

Source: Ohio State University [December 19, 2011]

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Research states that prejudice comes from a basic human need and way of thinking

Where does prejudice come from? Not from ideology, say the authors of a new paper. Instead, prejudice stems from a deeper psychological need, associated with a particular way of thinking. People who aren’t comfortable with ambiguity and want to make quick and firm decisions are also prone to making generalizations about others. 

In a new article published in Current Directions in Psychological Science, a journal of the Association for Psychological Science, Arne Roets and Alain Van Hiel of Ghent University in Belgium look at what psychological scientists have learned about prejudice since the 1954 publication of an influential book, The Nature of Prejudice by Gordon Allport. 

People who are prejudiced feel a much stronger need to make quick and firm judgments and decisions in order to reduce ambiguity. “Of course, everyone has to make decisions, but some people really hate uncertainty and therefore quickly rely on the most obvious information, often the first information they come across, to reduce it” Roets says. That’s also why they favor authorities and social norms which make it easier to make decisions. Then, once they’ve made up their mind, they stick to it. “If you provide information that contradicts their decision, they just ignore it.” 

Roets argues that this way of thinking is linked to people’s need to categorize the world, often unconsciously. “When we meet someone, we immediately see that person as being male or female, young or old, black or white, without really being aware of this categorization,” he says. “Social categories are useful to reduce complexity, but the problem is that we also assign some properties to these categories. This can lead to prejudice and stereotyping.” 

People who need to make quick judgments will judge a new person based on what they already believe about their category. “The easiest and fastest way to judge is to say, for example, ok, this person is a black man. If you just use your ideas about what black men are generally like, that’s an easy way to have an opinion of that person,” Roets says. “You say, ‘he’s part of this group, so he’s probably like this.’” 

It’s virtually impossible to change the basic way that people think. Now for the good news: It’s possible to actually also use this way of thinking to reduce people’s prejudice. If people who need quick answers meet people from other groups and like them personally, they are likely to use this positive experience to form their views of the whole group. “This is very much about salient positive information taking away the aversion, anxiety, and fear of the unknown,” Roets says. 

Roets’s conclusions suggest that the fundamental source of prejudice is not ideology, but rather a basic human need and way of thinking. “It really makes us think differently about how people become prejudiced or why people are prejudiced,” Roets says. “To reduce prejudice, we first have to acknowledge that it often satisfies some basic need to have quick answers and stable knowledge people rely on to make sense of the world.” 

Author: Divya Menon | Source: American Psychiatric Association [December 19, 2011]

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