DUJS Science News

Biology

Bacterial phenotypes are shaped by their host’s immune system

Dartmouth Medical School professors of microbiology and immunology William Wade and George O’Toole recently proposed that Gram-negative bacteria can recognize antibodies and immune effectors in their hosts, allowing the bacteria to modulate their phenotypes and virulence accordingly. The researchers offer criteria for assessing phenotypic regulation in a new approach to protect against bacterial diseases. Their work was published in Trends in Microbiology.

The new paradigm conveying the ability of bacteria to alter its phenotype in accordance with their hosts’ immune response may present a powerful approach to counteracting diseases. The researchers suggest that since cytokines cannot be targeted due to the vital role they play in the host’s defense system, outer membrane (OM) structures on bacteria are more practical targets for therapy. Antibodies derived from recombinant libraries can target the OM structures, resulting in phenotypes that lead to slower reproduction rates for bacteria and lower virulence. These antibodies may be delivered alone to the host or in conjunction with other antibiotics.

“This new concept may represent a means to reduce disease and start to turn pathogens into commensals,” said  Wade.

Medicine

Prevalence of psychiatric illness is found in older ethnic minority adults

Dartmouth Psychiatric Research Center researcher Daniel Jimenez and his team recently found a relationship between the prevalence of psychiatric illnesses and older ethnic minority adults of Latino and Asian ethnicities. The findings were published in the Journal of the American Geriatrics Society.

The researchers studied the growing number of immigrants aged 65 and older with Latino and Asian ancestry. The different psychiatric disorders were classified into four distinct categories: depressive disorder, anxiety disorder, substance disorder, or any assessed psychiatric disorder. Participants were asked about their psychiatric condition and to reflect on their English-speaking skills. All the ethnic and racial groups that participated in the study indicated that their English proficiency was either fair or poor, except for Afro-Caribbean respondents, who indicated that their English was either good or excellent.

The researchers found that depression in immigrants is primarily caused by a feeling of isolation stemming from an inability to speak English. Given the increasing age and diversity of immigrants to the US, the study was a step forward towards providing accurate health services and deepening an understanding of various cultures and the tendency towards psychiatric disorders.

New vaccine is found to prevent tuberculosis in HIV patients

Dartmouth professor of medicine Ford von Reyn and his research team recently found that a new tuberculosis vaccine, namely Mycobacterium vaccae (MV), is effective in helping prevent tuberculosis (TB) in HIV-infected individuals. The vaccine is particularly effective in those HIV-infected individuals with childhood Bacille Calmette-Guérin (BCG) immunization, the currently existing TB vaccine. The findings were published in AIDS.

The DarDar Health study led by von Reyn is named for Dartmouth and Dar es Salaam, Tanzania where the researchers found that MV immunization reduced the rate of definite TB by 37 percent among 2,013 HIV-infected patients. The researchers found that the administration of a multiple-dose series of MV to HIV-infected adults with childhood BCG immunization is safe and is associated with significant protection against definite tuberculosis.

“We are optimistic that the DarDar trial will lead to further development and eventual licensing of MV for use in the developing world,” said von Reyn.

Brain Sciences

Dartmouth researchers examine brain responses to social feedback

Humans often respond to social interactions by forming evaluations about themselves and the people around them. Self-esteem, an attitude based on positive or negative aspects of oneself, represents a major component of this response. Certain regions of the brain have been linked to social feedback, including the ventral anterior cingulate cortex (vACC) and the medial prefrontal cortex (mPFC). Dartmouth professor of psychological and brain sciences Todd Heatherton and his research team recently examined the brain response to social feedback. Their findings were published in Cerebral Cortex.

The research team examined neural responses to social feedback in low and high self-esteem individuals. The researchers found that there were inflated perceptions of liking in high self-esteem individuals relative to the realistic low self-esteem individuals. This lines up with prior work that has associated high self-esteem individuals with behavioral biases which lead to negative interpersonal feedback. When faced with social rejection, the high self-esteem individual is likely to emphasize his or her own positive features while derogating others.
The linkages between self-esteem and psychiatric health are numerous, with self-esteem being a risk factor for major depression. Finding the neurobiological correlates of risk factors for psychiatric illnesses may shed light on the pathophysiology of these illnesses.

Dartmouth professor encourages more neural research on socioeconomic status

Dartmouth professor at the Neukom Institute for Computational Science Rajeev Raizada has recently reviewed the current research, or lack thereof, of the effects of socioeconomic status (SES) on brain development and finds the field ripe for further investigation with both practical and scientific importance. The review was published in Frontiers in Human Neuroscience.

Raizada opens the window of opportunity for neuroimaging research. He finds that presently, there is a great disconnect between the large amount of behavioral data available that point to SES correlations with language, math, attention, memory and stress, and the scanty corresponding neural data which would help elucidate the underlying mechanisms. Neuro-imaging data can deepen our understanding of behavioral data, particularly in the area of intervention research. It can help predict the degree to which subjects benefit from a subsequent intervention.

“I wanted to emphasize the fact that this is a very under-researched area, with a lot of potential for new findings which are interesting not only scientifically, but also in terms of potentially helping to reduce educational inequality,” said Raizada.

Technology

Art forgeries spotted using sparse coding technology

Sparse coding technology has long been an important tool in neuroscience research, allowing scientists to quantitatively determine how optical information is represented by neurons in the brain. Dartmouth researchers James Hughes, Daniel Graham, and Daniel Rockmore in the computer science and math departments have recently extended its use to the field of quantitative art authentication, or stylometry.

The researchers developed the sparse coding model as an art authentication technology. They imagined a visual system that had evolved while being exposed only to Bruegel drawings. Thus, it would process Bruegel drawings using few filters but would have to use many more when looking at anything else-including Bruegel forgeries.

The sparse coding model developed by Dartmouth’s researchers discriminates between authentic and imitation artwork more accurately than many other authentication methods including wavelet techniques. However, the researchers stress that they do not expect their model to replace the expertise of art historians; rather it will be one of many technical tools at their disposal.

Chemistry

Structure of cholera bacteria regulator, ToxT, reveals new mechanism for infection treatment

Dartmouth chemistry professor F. Jon Kull and colleagues have recently solved the structure of ToxT, a protein regulator of the infectious bacterium Vibrio cholerae that is essential in causing the potentially fatal diarrheal disease of cholera. Their study may lead to a novel method in inhibiting infection of a disease afflicting nearly 300,000 people per year worldwide.

Using X-ray crystallography, the researchers uncovered the high resolution structure of ToxT, which surprisingly contains a 16-carbon fatty acid. The fatty acid inhibits expression of key virulence factors vital for cholera infection to produce disease for as long as the fatty acid remained attached to the ToxT regulator. The researchers found that the presence of oleic acids is what prevents ToxT from releasing this inhibitory fatty acid.

The research team proposed that providing individuals infected by the Vibrio cholerae bacterium with an increased supply of oleic acids or other similar compounds, preferably from a natural source, may serve as a possible mechanism to control the bacterium’s virulence.

Further, 44 billion people worldwide fall ill with infectious diarrhea each year, resulting in six to eight million subsequent deaths. “If these bacteria are all regulated in the same way and this natural treatment works for cholera,” says Kull, “It could work for all of these diseases as well. And that is a too big to believe deal.”