New Molecular Target Identified for Treating Cerebral Malaria

                                                             Mosquito Anopheles

A drug already approved for treating other diseases may be useful as a treatment for cerebral malaria, according to researchers at Harvard T. H. Chan School of Public Health. They discovered a novel link between food intake during the early stages of infection and the outcome of the disease, identifying two molecular pathways that could serve as new targets for treatment.

“We have known for a long time that nutrition can affect the course of infectious disease, but we were surprised at how rapidly a mild reduction in food intake could improve outcome in a mouse malaria model,” said senior author James Mitchell, associate professor of genetics and complex diseases. “However, the real importance of this work is the identification of unexpected molecular pathways underlying cerebral malaria that we can now target with existing drugs.”

The study appears online January 30, 2015 in Nature Communications.

Cerebral malaria — a severe form of the disease — is the most serious consequence of infection by the parasite Plasmodium falciparum, resulting in seizures, coma, and death. Currently there is a lack of safe treatment options for cerebral malaria, particularly for use in children, who represent the majority of cases. Even patients who receive early treatment with standard antimalarial chemotherapeutic agents run a high risk of dying, despite clearance of the parasite. Moreover, around 25% of survivors develop neurological complications and cognitive impairment.

Lead authors Pedro Mejia and J. Humberto Treviño-Villarreal, both researchers at Harvard T.H. Chan School of Public Health, found that leptin—a hormone secreted from fat tissue with roles in suppressing appetite, but also in activating adaptive immune and inflammatory responses—is increased upon infection in a mouse model of cerebral malaria, and turns out to be a major bad actor in promoting neurological symptoms and death. Remarkably, Mejia, Treviño-Villarreal and colleagues showed that reducing leptin using a variety of means, either genetically, pharmacologically, or nutritionally by reducing food intake during the first two days of infection, protected against cerebral malaria.

The researchers also found that leptin acted primarily on cytotoxic T cells by turning on the well-studied mTOR protein, for which pharmacologic inhibitors are readily available. In their animal model, treating mice with the mTOR inhibitor rapamycin protected them against the neurological complications of cerebral malaria. Protection was due in part to a preservation of the blood brain barrier, which prevented the entry of blood cells carrying the parasites into the brain. As rapamycin is already FDA-approved for use in humans, trials in humans for cerebral malaria treatment with this drug may be possible, according to the researchers.

This study was the result of an ongoing collaboration between the Mitchell lab in the Department of Genetics and Complex Diseases and the labs of Manoj Duraisingh and Dyann Wirth in the Department of Immunology and Infectious Diseases. Other Harvard T.H. Chan School of Public Health authors included  Christopher Hine, Eylul Harputlugil, Samantha Lang, Ediz Calay and Rick Rogers.

This study was supported in part by grants from NIH (DK090629 and AG036712) and the Glenn Foundation for Medical Research to J.R.M.; a Harvard T.H. Chan School of Public Health Yerby postdoctoral fellowship to Mejia, and financial support from the Universidad Auto´noma de Nuevo Leo´n to Treviño-Villarreal.

Source: Harvard

UA to Serve Up Fresh Approach to Health

The commitment of the Department of Nutritional Sciences to promoting and adapting Mediterranean diet principles will continue through all three areas of the University’s land grant mission: academic programs, research and Cooperative Extension outreach programs. Credit: UA

The Mediterranean diet has seen growing global popularity as researchers find that the dietary pattern can help prevent or reduce obesity, heart disease, type 2 diabetes and certain types of cancer.

Responsive to that popularity, the University of Arizona Department of Nutritional Sciences is hosting a series of events meant to explore and share current research related to the dietary pattern, which focuses on fresh fruits and vegetables, whole grains, beans and nuts, along with lesser amounts of lean fish, meats, dairy, olive oil and red wine.

"We want to emphasize how this pattern of eating has been demonstrated to contribute to disease prevention," said Donato Romagnolo, a professor in the Arizona Cancer Center and the nutritional sciences department, which is housed in the UA College of Agriculture and Life Sciences. 

National Geographic Blue Zones speaker Rudy Maxa, a Washington Post reporter and columnist, and five Tucson-area celebrity chefs will kick off the Jan. 28 opening-night reception, "A Food, Wine and Healthy Living Event," at the Tucson Museum of Art.

The 6-8 p.m. event is open to the public and will feature food prepared by the chefs, award-winning wine provided by the Arizona Wine Growers Association and live flamenco and Spanish guitar.

Then the UA will will host the Jan. 29-30 "Health Benefits of the Mediterranean Diet – Bringing Science to the Plate (With an Arizona Twist!)" scientific conference at the Student Union Memorial Center.

Supported in part by a grant from the U.S. Department of Agriculture, the conference is geared toward public health and nutrition professionals, nurses, physicians, physical therapists and chiropractors, and it is offered for continuing professional credit. The event is also open to students and features a student showcase.

A full agenda and registration for the conference are available online.

Promoting the health benefits of the Mediterranean lifestyle is just one of numerous initiatives sponsored by the UA Department of Nutritional Sciences to advance optimal health and well-being for Arizonans and to focus on ways of preventing and treating chronic diseases. 

After the conference, a four-part, hands-on cooking series will be offered to the public during February and March at the UA Cooperative Extension's Garden Kitchen, "The Many Faces of the Mediterranean Diet: Four Evenings," featuring the cuisines of Spain, France, Morocco and Italy. Information is available online. 

Also, the Mediterranean Diet and Health course will be offered for academic credit during summer 2015 (one week in Tucson and three weeks in Verona, Italy) for students through the UA Global Initiatives Study Abroad Program.

Much of the interest in the Mediterranean diet stems from evidence that it can reduce the risk of death associated with heart disease and cancer. Other research indicates that the diet can reduce the incidence of Parkinson's and Alzheimer's diseases.

Romagnolo, also the program director of the Mediterranean Diet and Health Study Abroad Program, said the benefits are especially important given pervasive health concerns across the nation. He noted that about 60 percent of people in the U.S. are overweight and 30 percent are obese.

"The latter is a risk factor for diabetes, cancer and metabolic syndrome," Romagnolo said.
During the conference, more than 20 presenters from the UA College of Agriculture and Life Sciences, the UA College of Medicine, national and international universities, institutes and organizations will talk. 

Presenters will cover four general areas: the Mediterranean diet and regional trends; obesity, diabetes and healthy aging; cancer prevention and control; and methods for translating science to the plate.

Live demonstrations by Arizona growers, vendors and educators will provide attendees with tasting opportunities, meal preparation ideas and information on where to find local products that help make healthful eating easy in the Southwest.

Also, prominent diet researchers from Spain, France and Greece will present current research on the health benefits of the traditional Mediterranean diet and offer ways to adapt it using local agricultural ingredients and cooking techniques. Speakers include:

Lluis Serra-Majem of the University of Las Palmas de Gran Canaria, Spain, who will present the keynote address on "The Mediterranean Diet as an Intangible and Sustainable Food Culture."

Mariette Gerber of the INSERM-Institut du Cancer de Montpellier, France, who will discuss "Implementing the Mediterranean Diet: The French Perspective." 

Antonia Trichopoulou of the University of Athens, Greece, who will speak on "Mediterranean Diet and Longevity."

"The conference is an opportunity to present ideas and concepts that may be adopted by the food industry, nutritionists, researchers and policymakers to help reduce the burden of these chronic diseases," Romagnolo said. "We want to show people how they can do it on their own and apply the basic tenets of the diet here in Arizona."

Source: University of Arizona

Mother's diet affects the 'silencing' of her child's genes

An infant from the Gambia. Credit: Felicia Webb

A mother's diet before conception can permanently affect how her child's genes function, according to a study published in Nature Communications.

The first such evidence of the effect in humans opens up the possibility that a mother's diet before pregnancy could permanently affect many aspects of her children's lifelong health.

Researchers from the MRC International Nutrition Group, based at the London School of Hygiene & Tropical Medicine and MRC Unit, The Gambia, utilized a unique 'experiment of nature' in rural Gambia, where the population's dependence on own grown foods and a markedly seasonal climate impose a large difference in people's dietary patterns between rainy and dry seasons.

Through a selection process involving over 2,000 women, the researchers enrolled pregnant women who conceived at the peak of the rainy season (84 women) and the peak of the dry season (83 women). By measuring the concentrations of nutrients in their blood, and later analysing blood and hair follicle samples from their 2-8 month old infants, they found that a mother's diet before conception had a significant effect on the properties of her child's DNA.

While a child's genes are inherited directly from their parents, how these genes are expressed is controlled through 'epigenetic' modifications to the DNA. One such modification involves tagging gene regions with chemical compounds called methyl groups and results in silencing the genes. The addition of these compounds requires key nutrients including folate, vitamins B2, B6 and B12, choline and methionine.

Experiments in animals have already shown that environmental influences before conception can lead to epigenetic changes that affect the offspring. A 2003 study found that a female mouse's diet can change her offspring's coat colour by permanently modifying DNA methylation.1 But until this latest research, funded by the Wellcome Trust and the MRC, it was unknown whether such effects also occur in humans.

Senior author Dr Branwen Hennig, Senior Investigator Scientist at the MRC Gambia Unit and the London School of Hygiene & Tropical Medicine, said: "Our results represent the first demonstration in humans that a mother's nutritional well-being at the time of conception can change how her child's genes will be interpreted, with a life-long impact."

The researchers found that infants from rainy season conceptions had consistently higher rates of methyl groups present in all six genes they studied, and that these were linked to various nutrient levels in the mother's blood. Strong associations were found with two compounds in particular (homocysteine and cysteine), and the mothers' body mass index (BMI) had an additional influence. However, although these epigenetic effects were observed, their functional consequences remain unknown.

Professor Andrew Prentice, Professor of International Nutrition at the London School of Hygiene & Tropical Medicine, and head of the Nutrition Theme at the MRC Unit, The Gambia, said: "Our on-going research is yielding strong indications that the methylation machinery can be disrupted by nutrient deficiencies and that this can lead to disease. Our ultimate goal is to define an optimal diet for mothers-to-be that would prevent defects in the methylation process. Pre-conceptional folic acid is already used to prevent defects in embryos. Now our research is pointing towards the need for a cocktail of nutrients, which could come from the diet or from supplements."

Dr Rob Waterland of Baylor College of Medicine in Houston, who conducted the epigenetic analyses said: "We selected these gene regions because our earlier studies in mice had shown that establishment of DNA methylation at metastable epialleles is particularly sensitive to maternal nutrition in early pregnancy."

The authors note that their study was limited by including only one blood sampling point during early pregnancy, but estimates of pre-conception nutrient concentrations were calculated using results from non-pregnant women sampled throughout a whole calendar year. The authors also plan to increase the sample size in further studies.

Source: London School of Hygiene & Tropical Medicine

Improving taste of alcohol-free beer with aromas from regular beer

Some aromatic substances from alcoholic beer can be extracted and added to alcohol-free varieties.

Consumers often complain that alcohol-free beer is tasteless, but some of the aromas it is lacking can be carried across from regular beer. Researchers from the University of Valladolid (Spain) have developed the technique and a panel of tasters has confirmed its effectiveness.

The alcohol in beer acts as a solvent for a variety of aromatic compounds; therefore, when it is eliminated, as in non-alcoholic beers, the final product loses aromas and some of its taste. It is difficult to recover these compounds, but researchers from the University of Valladolid have done just this using a pervaporation process.

"This technique consists in using a semipermeable membrane to separate two fractions from alcoholic beer: one liquid phase in which alcohol is retained, and another gaseous phase, where the aromatic compounds come in," Carlos A. Blanco, one of the authors explains. "Then, this gaseous phase can be condensed, the aromatic compounds extracted and added to non-alcoholic beer."

To conduct the study, the scientists used a special beer (with 5.5% alcohol) and another reserve beer (6.5%) from which they extracted three aromatic compounds: ethyl acetate, isoamyl acetate and isobutyl alcohol. They then added these substances to two 'almost' alcohol-free beers on the market: low-alcohol beer (less than 1% ABV) and alcohol-free beer (less than 0.1% ABV)..

A panel of experts tasted them. 90% of tasters preferred enriched low-alcohol beer instead of their original factory counterparts, and this percentage rose to 80% for alcohol-free beer. The figures have been published in the 'Journal of Food Engineering'.

"In light of these results, we conclude that the taste is improved, and thus the quality of this 'alcohol-free' beer, as the majority of panellists preferred the beer with aromas to the original," Blanco confirms.

The researchers recognise that this technique cannot yet capture all the aromas and tastes associated with alcoholic beer, but it does show progress in making 'alcohol-free' varieties more palatable for the consumer.

Spain is the primary producer and consumer of alcohol-free beer in the European Union. Around 13% of the beer sold in this country is alcohol-free, consumption of which has increased in recent years due to driving restrictions and for health reasons.

Source: Plataforma SINC

Fine particulate air pollution linked with increased autism risk

The greater the exposure a pregnant woman has to fine particulate matter, the greater the risk of their baby having autism, researchers found. Credit: © Oleg Shelomentsev / Fotolia

Women exposed to high levels of fine particulate matter specifically during pregnancy--particularly during the third trimester--may face up to twice the risk of having a child with autism than mothers living in areas with low particulate matter, according to a new study from Harvard School of Public Health (HSPH). The greater the exposure, the greater the risk, researchers found. It was the first U.S.-wide study exploring the link between airborne particulate matter and autism.

"Our data add additional important support to the hypothesis that maternal exposure to air pollution contributes to the risk of autism spectrum disorders," said Marc Weisskopf, associate professor of environmental and occupational epidemiology and senior author of the study. "The specificity of our findings for the pregnancy period, and third trimester in particular, rules out many other possible explanations for these findings."

The study appears online December 18, 2014 in Environmental Health Perspectives.

Prior studies have suggested that, in addition to genetics, exposure to airborne environmental contaminants, particularly during pregnancy and early life, may affect risk of autism. This study focused specifically on the pregnancy period.

The study population included offspring of participants living in all 50 states in Nurses' Health Study II, a cohort of more than 116,000 female U.S. nurses begun in 1989. The researchers collected data on where participants lived during their pregnancies as well as data from the U.S. Environmental Protection Agency and other sources on levels of fine particulate matter air pollution (PM2.5)--particles 2.5 microns in diameter or smaller--in locations across the U.S. The researchers identified 245 children who were diagnosed with autism spectrum disorder (ASD) and a control group of 1,522 children without ASD during the time period studied.

The researchers explored the association between autism and exposure to PM2.5 before, during, and after pregnancy. They also calculated exposure to PM2.5 during each pregnancy trimester.

Exposure to PM2.5 was significantly associated with autism during pregnancy, but not before or after, the study found. And during the pregnancy, the third trimester specifically was significantly associated with an increased risk. Little association was found between air pollution from larger-sized particles (PM10-2.5) and autism.

"The evidence base for a role for maternal exposure to air pollution increasing the risk of autism spectrum disorders is becoming quite strong," said Weisskopf. "This not only gives us important insight as we continue to pursue the origins of autism spectrum disorders, but as a modifiable exposure, opens the door to thinking about possible preventative measures."

Source: Harvard School of Public Health