Broccoli May Help Protect Against Respiratory Conditions Like Asthma

Here's another reason to eat your broccoli: UCLA researchers report that a naturally occurring compound found in broccoli and other cruciferous vegetables may help protect against respiratory inflammation that causes conditions like asthma, allergic rhinitis and chronic obstructive pulmonary disease.Published in the March edition of the journal Clinical Immunology, the research shows that sulforaphane, a chemical in broccoli, triggers an increase of antioxidant enzymes in the human airway that offers protection against the onslaught of free radicals that we breathe in every day in polluted air, pollen, diesel exhaust and tobacco smoke. A supercharged form of oxygen, free radicals can cause oxidative tissue damage, which leads to inflammation and respiratory conditions like asthma.

"This is one of the first studies showing that broccoli sprouts — a readily available food source — offered potent biologic effects in stimulating an antioxidant response in humans," said Dr. Marc Riedl, the study's principal investigator and an assistant professor of clinical immunology and allergy at the David Geffen School of Medicine at UCLA.

"We found a two- to three-fold increase in antioxidant enzymes in the nasal airway cells of study participants who had eaten a preparation of broccoli sprouts," Riedl said. "This strategy may offer protection against inflammatory processes and could lead to potential treatments for a variety of respiratory conditions."

The UCLA team worked with 65 volunteers who were given varying oral doses of either broccoli or alfalfa sprout preparations for three days. Broccoli sprouts are the richest natural source of sulforaphane; the alfalfa sprouts, which do not contain the compound, served as a placebo.

Rinses of nasal passages were collected at the beginning and end of the study to assess the gene expression of antioxidant enzymes in cells of the upper airways. Researchers found significant increases of antioxidant enzymes at broccoli sprout doses of 100 grams and higher, compared with the placebo group.

The maximum broccoli sprout dosage of 200 grams generated a 101-percent increase of an antioxidant enzyme called GSTP1 and a 199-percent increase of another key enzyme called NQO1.

"A major advantage of sulforaphane is that it appears to increase a broad array of antioxidant enzymes, which may help the compound's effectiveness in blocking the harmful effects of air pollution," Riedl said.

According to the authors, no serious side effects occurred in study participants receiving broccoli sprouts, demonstrating that this may be an effective, safe antioxidant strategy to help reduce the inflammatory impact of free radicals.

Riedl notes that more research needs to be done to examine the benefits of sulforaphane for specific respiratory conditions. It is too early to recommend a particular dosage.

Riedl recommends including broccoli and other cruciferous vegetables as part of a healthy diet.

The study was supported by the National Institutes of Health, the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency.

Other study authors include Dr. Andrew Saxon of the Hart and Louis Lyon Laboratory, division of clinical immunology and allergy in the department of medicine at the David Geffen School of Medicine at UCLA, and Dr. David Diaz-Sanchez of the human studies division of the U.S. Environmental Protection Agency.

Calculating Gene And Protein Connections In Parkinson's Disease Model

A novel approach to analyzing cellular data is yielding new understanding of Parkinson's disease's destructive pathways.Researchers have created an algorithm that meshes existing data to produce a clearer step-by-step flow chart of how cells respond to stimuli. Using this new method, Whitehead Institute and Massachusetts Institute of Technology scientists have analyzed alpha-synuclein toxicity to identify genes and pathways that can affect cell survival. Misfolded copies of the alpha-synuclein protein in brain cells are a hallmark of Parkinson's disease.

Until now, data on gene expression and protein production have not been consistently analyzed together, leaving gaps in researchers' understanding of how various genes and proteins interact to form a cell's response to a stimulus. This new method could speed the development of therapies for a variety of diseases, including Parkinson's disease.

The scientists have employed this new computational technique to analyze alpha-synuclein, a mysterious protein that is associated with Parkinson's disease.

Cells are constantly adapting to various stimuli, including changes in their environment and mutations, through an intricate web of molecular interactions. Knowledge of these changes is crucial for developing new treatments for diseases. To decipher how a cell responds to various stimuli, laboratories worldwide have been turning to new technologies that produce vast amounts of data. Such data typically exists in two major forms: genetic screen data (the results from deleting a gene from a cell's genome and seeing what observable traits appear in the cell) and information on the cellular levels of messenger RNA (mRNA, which is the template for proteins).

Historically, these two types of data have largely been analyzed independently of each other, revealing only glimpses of the cell's internal workings. Each type of data is actually biased toward identifying different aspects of cellular response, something that researchers had not realized until now. However, the new algorithm, known as ResponseNet, exploits these biases and allows for combined analysis.

In this combined analysis, both data types are integrated with molecular interactions data into a diagram that connects the experimentally identified proteins and genes. While this typically results in an extraordinarily complicated diagram, sometimes jokingly referred to as a "hairball", ResponseNet is designed to whittle the hairball down to the most probable pathways connecting various genes and proteins.

Esti Yeger-Lotem, a postdoctoral researcher in the laboratories of Whitehead Member Susan Lindquist and of Ernest Fraenkel at MIT's Biological Engineering department and co-author of the Nature Genetics article, says that by analyzing those probable pathways, a systems view of the cellular response emerges. "This allows for a more complete understanding of cellular response and can reveal hidden components of the response that may be targeted by drugs," she says.

According to Laura Riva, a postdoctoral researcher in MIT's biological engineering department and one of the designers of the algorithm, ResponseNet is potentially very useful for researchers.

"It is a powerful approach for interpreting experimental data because it can efficiently analyze tens of thousands of nodes and interactions," says Riva, who is also a co-author on the article. "The output of ResponseNet is a sparse network connecting some of the genetic data to some of the transcriptional data via intermediate proteins. Biologists can look at the network and understand which pathways are perturbed, and they can use it to generate testable hypotheses."

To demonstrate ResponseNet's capabilities, Yeger-Lotem entered the data from screens of 5,500 yeast strains (Saccharomyces cerevisiae). These strains are based on a yeast model that creates large amounts of the protein alpha-synuclein, thereby mimicking the toxic effects of alpha-synuclein accumulation in Parkinson's disease patients' brain cells.

Ernest Fraenkel, Assistant Professor of Biological Engineering at MIT, says that the alpha-synuclein data are an excellent test case for the algorithm, which has lead to new insights from existing data.

"The connection between alpha-synuclein and Parkinson's disease is enigmatic," says Fraenkel. "We have wonderful data from the yeast model, but despite this richness of data, so little is known about what alpha-synuclein really does in the cell."

Using these data, ResponseNet identified several links between alpha-synuclein toxicity and basic cell processes, including those used to recycle proteins and to usher the cell through its normal life cycle.

Surprisingly, ResponseNet also tied alpha-synuclein toxicity to a highly-conserved pathway targeted by cholesterol-lowering statin drugs and another pathway targeted by the immunosuppressing drug rapamycin.

To confirm ResponseNet's links and to test how these two pathways could affect alpha-synuclein toxicity, researchers added either rapamycin or the statin lovastatin to yeast model cultures. When the researchers added a low dose of rapamycin to the yeast model, the drug was toxic to the yeast. When lovastatin was added, the yeast reduced their growth rate, an indicator that the yeast had gotten sicker. However, when researchers added the molecule ubiquinone (also known as coenzyme Q10 or CoQ10), which is farther downstream in the statin network and possibly undersynthesized in alpha-synuclein-containing yeast, ubiquinone modestly suppressed alpha-synuclein toxicity.

All of these results validated the hypotheses based on ResponseNet's network.

"ResponseNet provides a wealth of new information," says Lindquist, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. "Some of the things we have found offer a promise to speed the development of new therapeutic strategies for Parkinson's disease. For the sake of the patients involved, let's hope they hold true in a human brain."

Full Citation: "Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity"

Nature Genetics, online February 22, 2009

Teenage Boys Who Eat Fish At Least Once A Week Achieve Higher Intelligence Scores

Fifteen-year-old males who ate fish at least once a week displayed higher cognitive skills at the age of 18 than those who it ate it less frequently, according to a study of nearly 4,000 teenagers published in the March issue of Acta Paediatrica.Eating fish once a week was enough to increase combined, verbal and visuospatial intelligence scores by an average of six per cent, while eating fish more than once a week increased them by just under 11 per cent.

Swedish researchers compared the responses of 3,972 males who took part in the survey with the cognitive scores recorded in their Swedish Military Conscription records three years later.

"We found a clear link between frequent fish consumption and higher scores when the teenagers ate fish at least once a week" says Professor Kjell Torén from the Sahlgrenska Academy at the University of Gothenburg, one of the senior scientists involved in the study. "When they ate fish more than once a week the improvement almost doubled.

"These findings are significant because the study was carried out between the ages of 15 and 18 when educational achievements can help to shape the rest of a young man's life."

The research team found that:

* 58 per cent of the boys who took part in the study ate fish at least once a week and a further 20 per cent ate fish more than once a week.
* When male teenagers ate fish more than once a week their combined intelligence scores were on average 12 per cent higher than those who ate fish less than once a week. Teenagers who ate fish once a week scored seven per cent higher.
* The verbal intelligence scores for teenagers who ate fish more than once a week were on average nine per cent higher than those who ate fish less than once a week. Those who ate fish once a week scored four per cent higher.
* The same pattern was seen in the visuospatial intelligence scores, with teenagers who ate fish more than once a week scoring on average 11 per cent higher than those who ate fish less than once a week. Those who ate fish once a week scored seven per cent higher.

"A number of studies have already shown that fish can help neurodevelopment in infants, reduce the risk of impaired cognitive function from middle age onwards and benefit babies born to women who ate fish during pregnancy" says Professor Torén.

"However we believe that this is the first large-scale study to explore the effect on adolescents."

The exact mechanism that links fish consumption to improved cognitive performance is still not clear.

"The most widely held theory is that it is the long-chain polyunsaturated fatty acids found in fish that have positive effects on cognitive performance" explains Professor Torén.

"Fish contains both omega-3 and omega-6 fatty acids which are known to accumulate in the brain when the foetus is developing. Other theories have been put forward that highlight their vascular and anti-inflammatory properties and their role in suppressing cytokines, chemicals that can affect the immune system."

In order to isolate the effect of fish consumption on the study subjects, the research team looked at a wide range of variables, including ethnicity, where they lived, their parents' educational level, the teenagers' well-being, how frequently they exercised and their weight.

"Having looked very carefully at the wide range of variables explored by this study it was very clear that there was a significant association between regular fish consumption at 15 and improved cognitive performance at 18" concludes lead author Dr Maria Aberg from the Centre for Brain Repair and Rehabilitation at the University of Gothenburg.

"We also found the same association between fish and intelligence in the teenagers regardless of their parents' level of education."

The researchers are now keen to carry out further research to see if the kind of fish consumed - for example lean fish in fish fingers or fatty fish such as salmon - makes any difference to the results.

"But for the time being it appears that including fish in a diet can make a valuable contribution to cognitive performance in male teenagers" says Dr Aberg.