Plutzer J.,National Institute of Environmental Health |
Ongerth J.,University of Wollongong |
Karanis P.,University of Cologne
International Journal of Hygiene and Environmental Health | Year: 2010
Giardia duodenalis (synonymous Giardia lamblia and Giardia intestinalis) is a flagellated protozoan parasite that reproduces in the small intestine causing giardiasis. It is a cosmopolitan pathogen with a very wide host range, including domestic and wild animal species, as well as human beings. In this paper the current knowledge about the taxonomy and phylogeny of G. duodenalis is summarized from the international literature and data on the detection and epidemiology are also reviewed concentrating on the last 20 years. Authors highlighted the current knowledge and some aspects on G. duodenalis in particular, water transmission and in vitro cultivation. The review sheds light on the difficulties of the strain differentiation and multilocus molecular analysis of Giardia strains especially when applied to water samples containing low numbers of cysts and components complicating the problem of tracking sources of contamination. Genetic elements determining or conferring traits such as infectivity, pathogenicity, virulence, and immune interaction contributing to clearance are currently not well established, if at all. These should be useful and important topics for future research. © 2010 Elsevier GmbH. Source
Researchers at MIT and the University of California at San Diego (UCSD) have recruited some new soldiers in the fight against cancer — bacteria. In a study appearing in the July 20 of Nature, the scientists programmed harmless strains of bacteria to deliver toxic payloads. When deployed together with a traditional cancer drug, the bacteria shrank aggressive liver tumors in mice much more effectively than either treatment alone. The new approach exploits bacteria’s natural tendency to accumulate at disease sites. Certain strains of bacteria thrive in low-oxygen environments such as tumors, and suppression of the host’s immune system also creates favorable conditions for bacteria to flourish. “Tumors can be friendly environments for bacteria to grow, and we’re taking advantage of that,” says Sangeeta Bhatia, who is the John and Dorothy Wilson Professor of Health Sciences and Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and its Institute for Medical Engineering and Science. Bhatia and Jeff Hasty, a professor of bioengineering at UCSD, are the senior authors of the paper. Lead authors are UCSD graduate student Omar Din and former MIT postdoc Tal Danino, who is now an assistant professor of biomedical engineering at Columbia University. The research team began looking into the possibility of harnessing bacteria to fight cancer several years ago. In a study published last year focusing on cancer diagnosis, the researchers engineered a strain of probiotic bacteria (similar to those found in yogurt) to express a genetic circuit that produces a luminescent signal, detectable with a simple urine test, if liver cancer is present. These harmless strains of E. coli, which can be either injected or consumed orally, tend to accumulate in the liver because one of the liver’s jobs is to filter bacteria out of the bloodstream. In their new study, the researchers delivered artificial genetic circuits into the bacteria, that allow the microbes to kill cancer cells in three different ways. One circuit produces a molecule called hemolysin, which destroys tumor cells by damaging their cell membranes. Another produces a drug that induces the cell to undergo programmed suicide, and the third circuit releases a protein that stimulates the body’s immune system to attack the tumor. To prevent potential side effects from these drugs, the researchers added another genetic circuit that allows the cells to detect how many other bacteria are in their environment, through a process known as quorum sensing. When the population reaches a predetermined target level, the bacterial cells self-destruct, releasing their toxic contents all at once. A few of the cells survive to begin the cycle again, which takes about 18 hours, allowing for repeated release of the drugs. “That allows us to maintain the burden of the bacteria in the whole organism at a low level and to keep pumping the drugs only into the tumor,” Bhatia says. The researchers tested the bacteria in mice with a very aggressive form of colon cancer that spreads to the liver. The bacteria accumulated in the liver and began their cycle of growth and drug release. On their own, they reduced tumor growth slightly, but when combined with the chemotherapy drug 5-fluorouracil, often used to treat liver cancer, they achieved a dramatic reduction in tumor size — much more extensive than if the drug was used on its own. This approach is well suited to liver tumors because bacteria taken orally have high exposure there, Bhatia says. “If you want to treat tumors outside the gut or liver with this strategy, then you would need to give a higher dose, inject them directly into the tumor, or add additional homing strategies,” she says. In previous studies, the researchers found that engineered bacteria that escape from the liver are effectively cleared by the immune system, and that they tend to thrive only in tumor environments, which should help to minimize any potential side effects. Martin Fussenegger, a professor of biotechnology and bioengineering at ETH Zurich, calls the new approach “unconventional” and “highly promising.” “This is a fascinating, refreshing, and beautiful concept,” says Fussenegger, who was not involved in the study. “In a world of mainstream cancer therapy concepts with often limited success, new therapy strategies are badly needed.” The researchers are now working on programming the bacteria to deliver other types of lethal cargo. They also plan to investigate which combinations of bacterial strains and tumor-targeting circuits would be the most effective against different types of tumors. The study was funded by the San Diego Center for Systems Biology, the National Institute of General Medical Sciences, the Ludwig Center for Molecular Oncology at MIT, an Amar G. Bose Research Grant, the Howard Hughes Medical Institute, a Koch Institute Support Grant from the National Cancer Institute, and a Core Center Grant from the National Institute of Environmental Health Sciences.
Having a lot of green around your home might help you live longer, according to a new study of more than 100,000 U.S. women. Women in the study with the most greenness near their homes — whether it was plants, trees and other vegetation — had a 12 percent lower death rate during the study period, compared with women who had the least amount of vegetation near their homes, the researchers found. "It is important to know that trees and plants provide health benefits in our communities, as well as beauty," Linda Birnbaum, director of the National Institute of Environmental Health Sciences, which funded the study, said in a statement. "The finding of reduced mortality suggests that vegetation may be important to health in a broad range of ways." For the study, researchers at the Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital in Boston looked at the level of vegetation around the homes of about 110,000 women who were registered nurses living across the United States, and were participating in a large ongoing research effort called the Nurses' Health Study. The participants had given their home addresses, and the researchers used satellite imagery to determine the amount of vegetation within 250 meters (820 feet) of their homes. Then, the researchers tracked the women from 2000 to 2008, during which there were 8,604 deaths. [Extending Life: 7 Ways to Live Past 100] Living in an area with a lot of vegetation was linked with a lower rate of death from any cause (excluding accidental injuries). Women living near areas with the most vegetation had a 41 percent lower death rate from kidney disease, a 34 percent lower death rate from respiratory disease and a 13 percent lower death rate from cancer, compared with women living in areas with the least vegetation, the study found. There are a number of reasons why vegetation near the home could lead to a longer life span, including providing space for physical activity or social gatherings, or decreasing stress and depression through contact with nature, the researchers said. Indeed, the study showed that women with lots of vegetation near their homes had lower levels of depression, and spent more hours participating in social groups such as charities, than people with less vegetation near their homes, suggesting that these were the biggest factors driving the link. The researchers took into account changes in vegetation around the home during the study period, as well as other factors that can affect mortality, such as a person's age, ethnicity or income level. The study was published April 14 in the journal Environmental Health Perspectives. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
The MIT Center for Environmental Health Sciences (CEHS), an interdisciplinary research center funded by the National Institute of Environmental Health Sciences (NIEHS), invites MIT faculty and research staff with principal investigator privileges to submit applications for funding of pilot projects related to environmental health, to support either basic or translational research. Please see the NIEHS strategic plan to gain understanding of the types of projects the center plans to fund. Preference is given to projects that address the NIEHS Strategic Goals. The center anticipates funding of $25,000 in direct costs for each project. The center encourages proposals from junior faculty, any faculty member wishing to branch into new areas of environmental health research, and faculty who are involved in interdisciplinary environmental health collaborations — for example between engineers and scientists. Projects can be anywhere on the spectrum between basic sciences and clinical translation. In all cases, the trajectory to human application must be clear and feasible. Translational pilot projects will be evaluated separately from those in the basic sciences. These projects are funded through the generosity of Vilma and Lionel Kinney, and are named in honor of Theron G. Randolph, a pioneer in the fields of environmental and natural products medicine. Applicants should submit a four-page research plan that outlines the specific aims and research strategy (i.e. significant, innovation, and approach). In the project title, please add a parenthesis indicating (Basic Research) or (Translational Research). Applications should also include a detailed budget form (Form Page 4), budget justification, and a biographical sketch using the NIH PHS398 forms. Completed applications should be submitted via email to Amanda Tat, administrative officer of the CEHS at email@example.com. Questions regarding the application process should be directed to Professor John M. Essigmann at firstname.lastname@example.org or Professor Bevin P. Engelward at email@example.com. Deadline for this call is June 30, with an anticipated start date of Sept. 1. Please visit the program website for more information.
A team of researchers from Colorado State University has been studying DNA damage in living cells to learn more about how genetic abnormalities arise. It has long been known that DNA molecules in every cell get constantly damaged by things from the outside environment, like sunlight, cigarette smoke and radiation. However, more recently researchers have discovered that sources from within the cell itself can sometimes be even more damaging. DNA, or deoxyribonucleic acid, is found in the nucleus of every cell. It is the code for the traits we have as human beings, and it serves as the warehouse of information needed to make a cell work. When something goes wrong with DNA, it can lead to a mutation and changes in the cell, and can sometimes lead to disease. In a study highlighted in a recent issue of Genetics, the team -- led by J. Lucas Argueso, CSU assistant professor and Boettcher Investigator in the Department of Environmental & Radiological Health Sciences -- found that RNA, or ribonucleic acid, has a new and important part in this process. CSU researchers worked in close in collaboration with scientists from the National Institute of Environmental Health Sciences in North Carolina. RNA is a molecule that plays a central role in the function of genes. It is the "business" end of a genome. The building blocks that cells use for making RNA are knows as ribonucleotides, which was the focus of the research paper. "You don't hear as much about RNA, but cells actually have much more RNA than DNA," Argueso said. Cells also have more ribonucleotides than deoxyribonucleotides, the building blocks for making DNA. Since the two are chemically very similar, it is quite common for cells to mistakenly incorporate RNA pieces into DNA. Argueso and his team -- including Hailey Conover, Ph.D. student in Cell & Molecular Biology and lead author of the study, and Deborah Afonso Cornelio, a post-doctoral researcher -- are looking at what happens to yeast cells when they are unable to accurately remove RNA from DNA. "The same problem happens in humans, carrots, butterflies, and yeast cells, the model organism used in our lab," Argueso said. "The same yeast that is used to bake bread and to brew beer is an incredibly useful biomedical research model." Findings from this study have direct implications for children with Aicardi-Goutieres syndrome, a devastating disorder that affects the brain, the immune system and the skin. "This is a very serious disease that affects children born without a critical enzyme that removes the RNA building blocks from DNA," Argueso said. "Our model yeast cells have been engineered to have the same basic genetic defect as Aicardi-Goutieres children so that we can investigate this problem at its very core." What's next for the team? Argueso said they want to extend their work to cancer research. The team wants to determine how ribonucleotides increase chromosome abnormalities and whether those increases are asymmetric, depending on which of the two strands of DNA the ribonucleotides are introduced. Most cancers have some form of alteration in chromosomal structure, though Argueso said that breast and ovarian cancers are by far the most affected by this issue. In addition, with some forms of chemotherapy that have been used for a long time, the mechanism of action is to decrease the production of DNA building blocks. "Cancer cells reproduce quickly," Argueso said. "To do that, the cells need DNA building blocks. Chemotherapy is used to decrease the building blocks. However, when you reduce the number of DNA building blocks, you push the cancer cells into a corner, where they end up putting in more RNA building blocks into the DNA." In other words, the very thing that the chemotherapy agent is encouraging cancer cells to incorporate causes them to acquire even more mutations. This could help explain why cancers often recur in more aggressive forms after someone goes into remission. "This unintended consequence could be one of the mechanisms making that happen," Argueso said.