Gene Is Likely Cause Of Stroke-Inducing Vascular Malformations

UCSF scientists have discovered that a gene controlling whether blood vessels differentiate into arteries or veins during embryonic development is linked to a vascular disorder in the brain that causes stroke.

The UCSF studies were done in mice, and the new findings are the first to provide information on both the progression and regression of this particular brain disorder, known as BAVM, and to provide molecular clues into the disease, which is not well-understood and chiefly affects young people.

BAVM, for brain arteriovenous malformation, is a vascular disorder causing arteries and veins to be directly connected, rather than through capillaries. This direct connection produces enlarged, tangled masses of vessels that are prone to hemorrhagic rupture, bleeding and stroke. Because they develop most often in growing tissues, BAVMs are responsible for half of the hemorrhagic strokes in children.

Study findings were published in a recent issue (Aug. 5, 2008) of the Proceedings of the National Academy of Sciences.

The UCSF team identified the gene, known as Notch, as a potential cause of BAVMs because of its role in directing embryonic blood vessel formation. Using genetic tools, the team “turned on” a constantly active Notch gene in endothelial brain cells, which are the cells lining blood vessels in the brain, and found that BAVMs were induced. When researchers turned the gene off, the mice exhibited full recovery from the disease’s progression.

“This was exciting. The activated Notch gene caused BAVM in all of the mice, making it an unprecedented, potent molecular lesion in the induction of the pathology,” said Rong Wang, PhD, senior author on the study, associate professor and director of the Laboratory for Accelerated Vascular Research and Mildred V. Strouss Endowed Chair in Vascular Surgery at UCSF. “Furthermore, we found that repression of the gene in already-ill mice led to their recovery.”

Approximately one million people worldwide suffer from BAVMs, though very little is known about the molecular mechanisms that cause them. Results from an ongoing clinical trial funded by the National Institutes of Health on the effectiveness of brain surgery, the only treatment option for the disease, questions whether the risks associated with surgery outweigh the risk of “waiting for a rupture,” the UCSF researchers say.

“Our study offers hope for future treatments because even the effects of stroke such as paralysis and ataxia, or loss of muscle coordination, were reversed once we turned off Notch,” said Patrick A. Murphy, lead author on the paper and a graduate student from the UCSF Biomedical Science Program, working with Wang. “This pathway has not yet been implicated in human disease, so these findings prompted our ongoing research into Notch signaling and allow us to examine the cellular and molecular mechanisms of BAVM.”

Knowledge gained about development of BAVM may also shed light on the process of blood vessel disease in other organs like the lung and liver, according to the UCSF team. “In the future, we may be able to inhibit or even reverse the disease process,” said Tyson Kim, co-author on the paper and a bioengineering graduate student from the UCSF MD/PhD combined program, working with Wang.

Based on the study findings, the UCSF team now considers Notch a strong candidate as a key regulator of human BAVM and is undertaking additional research to find the disease’s cause. In addition to using the mouse model to study disease progression and regression, Wang and colleagues also are studying the gene’s role in human AVMs by examining levels of Notch signaling pathway molecules in surgical tissue samples.

“Although more work needs to be done to determine whether the research can be applied to clinical practice and whether up-regulation of Notch causes BAVM and stroke in humans, identifying the role of this pathway offers hope for developing treatments for this and other related diseases,” Wang said.

Notes:

The research was funded by the Foundation for Accelerated Vascular Research, American Heart Association, estate of Mildred V. Strouss, Campini Foundation, and NIH.

Additional co-authors were Michael T. Y. Lam, Xiaoqing Wu, Shant M. Vartanian, Andrew W. Bollen, and Timothy R. Carlson of UCSF’s Pacific Vascular Research Laboratory.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Source:
Lauren Hammit
University of California – San Francisco

Muscle Mass/Strength Increased By Ibuprofen Or Acetaminophen In Long-Term Resistance Training

Taking daily recommended dosages of ibuprofen and acetaminophen caused a substantially greater increase over placebo in the amount of quadriceps muscle mass and muscle strength gained during three months of regular weight lifting, in a study by physiologists at the Human Performance Laboratory, Ball State University.

Dr. Chad Carroll, a postdoctoral fellow working with Dr. Todd Trappe, reported study results at Experimental Biology 2008 in San Diego on April 6. His presentation was part of the scientific program of the American Physiological Society (APS).

Thirty-six men and women, between 60 and 78 years of age (average age 65), were randomly assigned to daily dosages of either ibuprofen (such as that in Advil), acetaminophen (such as that in Tylenol), or a placebo. The dosages were identical to those recommended by the manufacturers and were selected to most closely mimic what chronic users of these medicines were likely to be taking. Neither the volunteers nor the scientists knew who was receiving which treatment until the end of the study.

All subjects participated in three months of weight training, 15-20 minute sessions conducted in the Human Performance Laboratory three times per week. The researchers knew from their own and other studies that training at this intensity and for this time period would significantly increase muscle mass and strength. They expected the placebo group to show such increases, as its members did, but they were surprised to find that the groups using either ibuprofen or acetaminophen did even better. An earlier study from the laboratory, measuring muscle metabolism (or more precisely, muscle protein synthesis, the mechanism through which new protein is added to muscle), had looked at changes over a 24 hour period. This “acute” study found that both ibuprofen and acetaminophen had a negative impact, by blocking a specific enzyme cyclooxygenase, commonly referred to as COX.

But that study looked at only one day. Over three months, says Dr. Trappe, the chronic consumption of ibuprofen or acetaminophen during resistance training appears to have induced intramuscular changes that enhance the metabolic response to resistance exercise, allowing the body to add substantially more new protein to muscle.

The amount of change was measured in quadricep muscles using Magnetic Resonance Imaging (MRI), the gold standard for determining muscle mass. The researchers now are conducting assays of muscle biopsies taken before and after the three-month period of resistance training, in order to understand the metabolic mechanism of the positive effects of ibuprofen and acetaminophen.

One of the foci of Ball State’s Human Performance Laboratory is the adaptation of the elderly to exercise. Another is the loss of muscle mass that takes place when astronauts are exposed to long-term weightlessness. This work has implications for both groups, says Dr. Trappe.

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In addition to Dr. Carroll and Dr. Trappe, co-authors of the Experimental Biology presentation are Jared Dickinson, Jennifer Lemoine, Jacob Haus, and Eileen Weinheimer, graduate students working with Dr. Trappe, and study physician Dr. Christopher Hollon.

Funding for the research came from the National Institutes of Health and a postdoctoral initiative award from APS.

Source: Sylvia Wrobel

Federation of American Societies for Experimental Biology

Aspirin Plus Plavix Disappoints In Heart Attack Prevention

According to researchers at the American College of Cardiology’s Annual Congress yesterday, aspirin may help people who have already had a heart attack. However, if you have never had a heart attack, aspirin may not be that useful in preventing one.

The researchers had carried out a study on combining aspirin with Plavix, a blood-thinning drug. They found that there was no benefit for preventing heart attacks, except for people who already had heart disease – even then the benefit was modest.

This 28-month study looked at 15,600 patients over the age of 45. Apart from finding no evidence of protection from heart attack or stroke, there were indications smokers and patients with diabetes may actually be harmed.

You can read about this trial in the New England Journal of Medicine.

Deepak Bhatt, M.D., Cleveland Clinic, spoke on behalf of colleagues in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial.

View drug information on Plavix.

New Report From Australian Researchers Concerned About The Planet, Places And People At Risk

Australians face increasingly large-scale health risks from our expanding impact on the natural environment, ranging from increases in weather extremes and dengue fever to obesity, diabetes and mental health.

Twelve of Australia’s top health and medical researchers have contributed to a new report which concludes that rapid environmental and climatic changes pose increasing risks to the health of Australians.

Released by Research Australia, the ‘Healthy Planet, Places and People’ Report found that:

* Deaths from heart attacks, strokes and respiratory disease, from increases in heatwaves, could double or triple by 2050;

* Asthma — already affecting 3 in 20 children and 1 in 10 adults — is likely to increase in some groups;

* The incidence and geographic range of some mosquito-borne infectious diseases will increase;

* Food poisoning — with 5.4 million cases reported each year — is also likely to rise;

* Viral infections such as avian flu and SARS will spread more readily as population density, people movement, trade and land clearing increase.

Professor Tony McMichael of the Australian National University, who led the report and is part of the Nobel Prize winning UN Intergovernmental Panel on Climate Change, said that researchers are just beginning to recognise the health implications of a warmer planet.

“Our rapidly expanding impact on the natural environment is casting a huge shadow over the health of future generations,” Prof McMichael said.

“It is not just a warmer planet and weather disasters — climate change is one of many environmental changes. Our health is also endangered by depleted water flows, land degradation, disrupted ecosystems and acidified oceans. We need better understanding of these risks, and how to reduce them, through new research.”

The report was commissioned by Research Australia to commemorate ‘Thank You’ Day (November 20, 2007), Australian’s annual opportunity to send personal messages of thanks to medical researchers whose work is special to them via thankyouday/.

2007 Australian of the Year, Prof Tim Flannery said it is hardly surprising that human health will be strongly influenced by climate change.

“From water availability and quantity to temperature and food, our changing climate will influence all of the fundamentals of life,” Prof Flannery said. Proudly supported by

“To ignore climate change in terms of human health would be a bit like treating the fish in a fishbowl, while refusing to change their ever more polluted water.”

Prof McMichael said health and medical research has long been based on the premise that the natural world around us is essentially constant.

“Today, human actions are inadvertently impairing the working of the world. We need to understand more about how human-induced changes to climate and global environment are affecting, and will affect, our lives,” Prof McMichael said.

The report was launched by Research Australia CEO, Rebecca James, who said the report’s findings highlight the importance of health and medical research in helping Australians adapt to the changing environment.

“We are only beginning to recognise the health implications of a warmer planet. More research is needed to understand its full impact on our health, and how we can adapt,” Ms James said.

“The potential health impacts of climate change are significant. Without the work of medical researchers to address health risks, the impact on our health, economy and society could be dramatic.”

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A full copy of the ‘Healthy Planet, Places and People’ Report can be downloaded from thankyouday/. From October 29 to November 20, you can also send your personal message of thanks to Australia’s health and medical researchers via the website. MBF Australia and NHMRC are diamond sponsors of ‘Thank You’ Day.

Researchers from ANU, CSIRO, Queensland Institute of Medical Research, University of Western Australia, University of Western Sydney, Macquarie University, University of Adelaide, QUT, Monash University, Charles Darwin University and the University of Newcastle contributed to the Report and are available for interviews. Research Australia is a unique national not-for-profit alliance of more than 190 member and donor organisations with a common mission to make health and medical research a higher national priority. For more information on Research Australia visit researchaustralia/.

“Thank You” Day events are being held in Sydney (Oct 29), Canberra (Oct 31), Gold Coast (Nov 2), Townsville (Nov 5), Darwin (Nov 7), Hobart (Nov 8), Perth (Nov 12), Melb (Nov 14 & 20), Brisbane (Nov 15) and Adelaide (Nov 15).

Source: Julie Sheather

Research Australia

Functional Amino Acids Regulate Key Metabolic Pathways

Functional amino acids play a critical role in the development of both animals and humans, according to a Texas AgriLife Research scientist.

In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to “think out of the box” and place more emphasis on this area of study.

“We need to move forward and capitalize on the potential of functional amino acids in improving health and animal production,” he said.

A functional amino acid is an amino acid that can regulate key metabolic pathways to improve health, growth, development and reproduction of animals and humans, Wu said.

“This involves cell signaling through amino acids and their metabolites, and the metabolic pathways may include protein synthesis, antioxidative reactions and oxidation of energy substrates,” he said. “A functional amino acid can be either a ‘nonessential’ or an ‘essential’ amino acid.”

Past research emphasis has focused primarily on essential amino acids. However, Wu says both essential amino acids and non-essential amino acids should be taken into consideration.

“This is important when formulating balanced diets to maximize growth performance in livestock species, poultry and fish,” he said. “It is also recommended that nonessential amino acids be provided to humans to prevent growth retardation and chronic diseases.”

Wu’s previous research discovered that arginine, an amino acid, contributes many positive benefits in growth and embryo development in pigs, sheep and rats. Arginine also aids in fighting obesity. Wu has identified this as an important area for expanded research on new amino acids and health.

“Currently in the U.S., more than 60 percent of adults are overweight or obese,” he said. “Globally, more than 300 million adults are obese and more than 1 billion are overweight. Also, a large number of children in the U.S. and other countries are overweight or obese. The most urgent needs of new research in amino acids and health are the roles of functional amino acids in the treatment and prevention of obesity and its associated cardiovascular dysfunction.”

Wu also said that dietary supplementation with arginine can help improve meat quality in pigs prior to slaughter.

The two top scientific discoveries in the field of amino acids and health over the past two decades are nitric oxide synthesis from arginine and the role of amino acids in cell signaling.

“An important area of research in the next few years may be to study the molecular and cellular mechanisms whereby some amino acids (e.g., arginine) can regulate metabolic pathways in animals and humans,” he said. “An example is how arginine reduces obesity and ameliorates the metabolic syndrome, and how elevated levels of leucine may contribute to mitochondrial dysfunction and insulin resistance (including vascular resistance) in obese subjects.”

He said “unquestionably” recent advances in understanding functional amino acids are “expanding our basic knowledge of protein metabolism and transforming practices of nutrition worldwide.”

Though nutritional studies conducted on animals have benefited human health, Wu suggests that caution should be taken to “extrapolate animal data to humans” as dietary requirements differ from one species to another.

Wu said that humans need diets with balanced portions of amino acids for cardiovascular and reproductive health.

Source:
Dr. Guoyao Wu
Texas A&M AgriLife Communications

56% Of Adults Support Easing Federal Embryonic Stem Cell Research Funding Restrictions, Poll Says

About 56% of U.S. adults support easing restrictions on federal funding for human embryonic stem cell research, according to an Associated Press-AOL poll conducted from Dec. 19, 2006, to Dec. 21, 2006, the AP/Washington Post reports (Superville, AP/Washington Post, 1/3). The poll also found that 43% opposed easing the restrictions (Associated Press/AOL Poll, 12/21/06). Federal funding for embryonic stem cell research is allowed only for research using embryonic stem cell lines created on or before Aug. 9, 2001, under a policy announced by President Bush on that date. Bush in July 2006 vetoed the Stem Cell Research Enhancement Act of 2005 (HR 810), which would have expanded stem cell lines that are eligible for federal funding and allowed funding for research using stem cells derived from embryos originally created for fertility treatments and willingly donated by patients. Democratic congressional leaders this month plan to approve a bill similar to the Stem Cell Research Enhancement Act (Kaiser Daily Women’s Health Policy Report, 11/30/06). According to the AP/Post, supporters of embryonic stem cell research say it could lead to treatments for conditions such as Parkinson’s disease and spinal cord injuries, while opponents of the research say human embryos should not be destroyed for research purposes. The poll was conducted by Ipsos and has a margin of error of about three percentage points (AP/Washington Post, 1/3).

The poll is available online. Note: You must have Adobe Acrobat to view the survey.

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

London Asthma Sufferers Get Space-based Help

The city of London has launched an innovative service, funded by ESA, which delivers air pollution alerts and health advice via SMS text messages to those who suffer from asthma and other conditions vulnerable to poor air quality.

The airTEXT service officially kicked off at London’s City Hall pn Thursday with the Deputy Mayor of London Nicky Gavron addressing the event: “There’s more than love in the air this spring! Air pollution causes around one thousand premature deaths each year, and we must do everything we can to cut emissions. “This pioneering service will provide people with crucial information about peak periods of air pollution localised for their part of London, so they can take action. It could literally save lives.”

AirTEXT is a free service aimed at those who have been diagnosed with asthma, emphysema, bronchitis, heart disease or angina as well as for those who live or work in London. The service has operated in the Borough of Croydon, the largest borough by population, since July 2005 and has received a positive response with 80 percent of users saying it has helped them manage their symptoms better and reduce their exposure to air pollution.

Subscribers can choose whether they want airTEXT alerts delivered through SMS text messages, voicemail or e-mail and whether they want to receive the alerts the morning of days when air pollution is likely to be higher than normal or the evening before. Forecasts are generated for each London borough.

Messages will indicate moderate, high or very high levels of pollution are expected, what effects are likely to be noticed, such as wheezing, difficulty in breathing or chest pains, and what should be done to minimise the effects, such as avoiding long periods outdoors, avoiding strenuous outdoor activity and increasing the dose of reliever medication as directed by a physician.

The Cambridge Environmental Research Consultants (CERC) developed airTEXT using information from ESA’s PROMOTE project, which aims to improve air-quality forecasting using satellite technology. In addition, PROMOTE aims to construct and deliver a sustainable and reliable operational service to support informed decisions on the atmospheric policy issues of stratospheric ozone depletion, surface ultraviolet (UV) exposure, air quality and climate change.

PROMOTE, PROtocol MOniToring for the GMES Service Element on Atmospheric Composition, is itself part of Global Monitoring for Environment and Security (GMES), a joint initiative between ESA and the European Commission to combine all available space- and ground-based information sources to develop an independent European environmental monitoring capacity from planetary to local scales.

The airTEXT service works by combining satellite data from ESA’s Envisat on regional air quality forecasts provided by PROMOTE with information on local road traffic patterns and monitoring stations around the city. Regional air quality information is important because not all the pollution affecting a city actually originates there. Depending on the weather, studies show that up to half the air pollution found in some European cities might have come from elsewhere in the continent.

“Previously air pollution forecasts have focused on very large geographical areas and the methods for communicating the information have been poor,” CERC atmospheric scientist Dr Iarla Kilbane-Dawe said. “AirTEXT represents a revolution in air-pollution forecasting with localised information being sent directly to the individual.”

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Contact: Mariangela D’Acunto
European Space Agency

Flu Vaccination For Poultry Workers – Leaflet, Q&A Sheet, And Directions, UK

The Department of Health is offering flu vaccination this winter to those who work in close contact with poultry. This is being done as a precautionary public health measure and does not mean that workers are at any higher risk of getting flu this winter than usual. Nor does it mean that there is an increased risk of an outbreak of bird flu in the UK as this risk remains low.

For further information please see the leaflet,Q&A sheet, and Directions at the links below.

– Flu vaccination for poultry workers – Leaflets

– Download Flu immunisation programme for people who work in close contact with poultry – Q&A (PDF, 64K)

– The Primary Medical Services (Influenza Immunisation Scheme for Poultry Workers) Directions 2007

– Guidance on the implementation of a seasonal flu vaccination programme

– Download Flu immunisation programme for poultry workers – consent form (PDF, 30K)

– Download Poultry premises for England (Map) (PDF, 256K)

– Download Vaccine supply order form (PDF, 54K)

Flu key documents

Flu documents and resources for patients and health professionals. Includes frequently asked questions, anti-viral agent information, contingency plans and immunisation publicity campaigns.
– Flu key documents

Flu FAQ

Frequently asked questions about flu immunisation policy, vaccine and the implementation of policy.
– Flu FAQ

Flu useful links

Links to web pages about influenza.
– Flu useful links

Department of Health (UK)

Some 70 Percent Of Schoolchildren Don’t Walk To School, Canada

Days when schoolchildren walked to neighbourhood schools are long gone. A new study by a team of researchers led by Paul Lewis, a professor of Urban Planning at the UniversitГ© de MontrГ©al, shows that only 30 percent of children attending elementary school reach school on foot or by bicycle.

The study was conducted from 2006 to 2008 in the central neighbourhoods and suburbs of two target regions: Montreal, the biggest metropolitan area of Quebec, and Trois-RiviГЁres, a medium-sized city. The parents of 1495 children attending 67 schools were surveyed for this investigation.

A public health problem for children

“The primary goal of the study was to identify the obstacles to why elementary pupils do not walk and bicycle to school and aren’t physical activity for the recommended 60 minutes per day,” says Dr. Lewis, who conducted this study with eight colleagues from the Group de recherche Ville et mobilitГ© (City and mobility research group).

The research team began their investigation by consulting past studies on the subject. According to Kino-QuГ©bec, in 1971, about 80 percent of Canadian children aged 7 and 8 walked to school. The Ville et mobilitГ© study conducted in 2008 revealed that the number of children who regularly walk or bicycle to school in the morning is around 30 percent of all children in the Montreal and Trois-RiviГЁres regions. What’s more, 80 percent of those who walk to school travel less than 600 meters.

Why are children walking less?

“The decrease in walking and bicycling in Western societies is the consequence of a general trend towards sedentary lifestyles,” Dr. Lewis says. “This decline is explained by urban sprawl, greater distance to travel to more activities and modern schedules featuring tighter time-management.”

The survey confirms the strongly dissuasive effect of home to school distance, which is due to the proliferation of special-purpose public schools and the strong presence of private schools. Indeed, attending neighbourhood schools is no longer the norm and kids travel farther for their education.

Another fundamental causes of the decline is how the majority of parents surveyed travel by car and do not set a good example for their children. “Even when the school is 300 meters away, some parents drive their children because it is on their way or they are leaving at the same time,” stresses Dr. Lewis. “Parents fear for their children’s safety in high urbanized environments. Safety takes precedence over health.”

How can children be encouraged to walk?

Although the study did not establish an action plan, the research team nonetheless has recommendations to encourage walking and bicycling by schoolchildren:

- Education boards should promote physical activity and walking should be factored when deciding to close or open a school or when designating schools with special programs.

- Existing urban frameworks must be radically altered to make them safer for children and adults: school zones should be made safer and planning measures should focus on entire urban environments to improve safety conditions where people are likely to circulate.

- It is imperative to restore spaces sacrificed for motorized traffic to pedestrians and cyclists.

- Public transit must be bolstered and speed limits should be stricter for motorists.

- Mothers and fathers should set an example for their children by having at least one parent walk or use public transit to commute.

- More parents need to be convinced of the importance of walking for daily energy expenditure and to foster greater autonomy in kids, whether kids walk alone or accompanied.

On the Web:

- The report is available in English in PDF format at villeetmobilite.

- The report can also be consulted in English thanks to the contribution of Transport Canada.

- About the UniversitГ© de MontrГ©al.

Partners in research:

The research was conducted by Groupe de recherche Ville et mobilitГ© between 2006 and 2008 as part of the Actions concertГ©es program on “Development of public policies favorable to acquisition and maintenance of healthy lifestyles.”

The Fonds quГ©bГ©cois de la recherche sur la sociГ©tГ© et la culture (FQRSC), in partnership with the Fonds de recherche en santГ© du QuГ©bec (FRSQ), the MinistГЁre de la santГ© et des services sociaux (MSSS) and the Centre de recherche en prГ©vention de l’obГ©sitГ© (CRPO). The MinistГЁre des transports du QuГ©bec (MTQ) and the Institut national de santГ© publique du QuГ©bec (INSPQ) research.

UniversitГ© de MontrГ©al

How Pathogens Hijack Host Plants Has Implications For Diabetes Research

Infestation by bacteria and other pathogens result in global crop losses of over $500 billion annually. A research team led by the Carnegie Institution’s Department of Plant Biology developed a novel trick for identifying how pathogens hijack plant nutrients to take over the organism. They discovered a novel family of pores that transport sugar out of the plant. Bacteria and fungi hijack the pores to access the plant sugar for food. The first goal of any pathogen is to access the host’s food supply to allow them to reproduce in large numbers. This is the first time scientists have a direct handle on controlling the food supply to pathogens and thus a new means to prevent a wide range of crop diseases and losses.

Mutation of the pore-protein genes prevents pathogen infection, such as blight in rice plants. In the absence of a pathogen, the pore proteins, called SWEETs, supply sugars to the developing pollen and may even be the long sought suppliers of nectar in flowers. The researchers found that humans and animals make a similar pore protein, which may play a role in the release of sugars from cells of the intestine, liver, testes, and mammary cells in animals including humans. Studies describing the fluorescence resonance energy transfer (FRET) sensor-based technology for identifying the pore proteins appeared in FASEB Journal (April 2010) and the Biochemical Journal (Sept 2010). The identification of the novel transporters is published in the November 25, 2010, issue of Nature.

Li-Qing Chen, the lead author of the study, explains the pathogenic process: “The primary goal of a pathogen is to tap the plants nutrient resources. They enter the spaces between the cells where they camp out, feed, and reproduce. Pathogenic bacteria inject activator proteins into the cell that directly induce expression of what we call sugar efflux transporters. Our novel sugar transporters – little flood gates that release sugar from the cell – at the cells’ plasma membrane, turn out to be essential for bacterial reproduction. Without food, bacteria can’t divide and amplify and thus cannot infect other plants.”

Previous to this study, the same lab had identified import mechanisms that drive sugar into cells, and has been searching for the elusive a sugar-pumping mechanism that exports sugar out of cells.

Plants convert energy from sunlight into sugar to nurture pollen, seeds, and nectar and cultivate beneficial microbes in the soil. The researchers work with plants containing FRET sugar nanosensors led them to the hypothesis that yet unknown sugar pores must be present in plants. The researchers looked for potential sugar transporters by screening for genes that might create pore-like activities in the cell membrane in Arabidopsis, a relative to mustard that is widely used for research.

They expressed these genes together with their FRET sensors in human cells that are very inefficient in taking up sugars and thus the nanosensors did not report sugar transport. However, when sugar pore genes are expressed with the nanosensors, the researchers obtain an optical report of sugar transport into the cell. The novel pore proteins in Arabidopsis turned out to have counterparts in rice, the worm C. elegans, and humans.

The scientists then found that pathogenic bacteria and fungi causing powdery mildew disease hijacked different SWEET family members to access to the plant’s nutrient resources. The SWEET genes are the cousins of one of the most important rice blight resistance genes used widely all across Asia to prevent blight infections. The researchers showed that the rice resistance gene Xa13, which had originally been identified by Frank White’s group from Kansas and Shiping Wang’s lab from Huazhong Agricultural University, China, also functions as a sugar pore. When production of the pore is suppressed, the plant becomes resistant to a blight bacteria. This result suggests to the researchers that the protein supplies sugar to the bug during infection. Since different pathogens try to hijack different pore genes, a drug that can block the activity of all SWEET cousins at the same time would turn off sugar supply to a pathogen that requires its host to live. Such a drug might be a powerful new way to reduce crop losses to a wide spectrum of pathogens. The research changes the perspective of plant-pathogen researchers by getting to the root of the process of infection. Understanding this process will advance infection prevention research against a wide variety of pathogens – bacterial and fungal.

Sugar efflux has been a mystery in human and animal systems as well. It is required in our intestine to transfer food-derived sugars to our blood stream and from the liver during fasting to keep glucose levels in the blood constant. The fact that the researchers also found a similar gene HsSWEET1 in humans that mediates sugar outflow in the liver and intestine suggests that study of this gene could open up a new avenue for diabetes research.

“These discoveries, made in the model plant Arabidopsis, have opened up an entirely new line of investigation for better crop protection techniques. Specifically, plant breeding and genetic changes that prevent hijacking of the pore function may serve to provide resistance to some problematic plant diseases,” remarked Frank White from Kansas University, a coauthor of this study. “Since the same genes are shared in many different organisms, including people, these genes could also be important to medicine.”

Source:
Wolf B. Frommer
Carnegie Institution