Clocks Are Ticking and Climate Is Changing: Increasing Plant Productivity in a Changing Climate (Eagle Group- Nov 17, 2012)

"If you know that the sun is going to go down, and if you are a photosynthetic plant, you have to readjust your metabolism in order to make it through the night," says McClung, the Patricia F. and Williams B. Hale 1944 Professor in the Arts and Sciences.

Seeking Knowledge Among the Weeds

McClung uses the Arabidopsis plant in his research on the mechanisms that affect plant behavior and its genetics. He jokingly refers to it as "an inconsequential little weed," but holds it in high esteem as an experimental test bed.

According to the National Institutes of Health, this member of the mustard family is the model organism for studies of the cellular and molecular biology of flowering plants. "Because plants are closely related, it is quite likely that knowledge derived from Arabidopsisstudies can be readily transferred to agronomically important species," says McClung.

Water and the Changing Climate

McClung sees internal clocks as increasingly important in the face of global climate change, and to agricultural productivity in particular. "In the context of climate change and the need to exploit increasingly marginal habitats, fuller understanding of clock mechanisms may offer strategies to improve crop productivity," says McClung. "We need to know how an organism measures time and how it uses that information to coordinate its physiology and behavior."

Water is the landscape on which biological clocks and climate change intersect. Agriculture consumes the vast majority of our water, and warmer and dryer conditions are predicted for much of the agricultural land of the United States. This is based on our current understanding of the changes predicted to be associated with global warming, and in this scenario our aquatic resources will become increasingly scarce.

Water is lost during the gas exchange that takes place in photosynthesis -- carbon dioxide in, oxygen out -- through small pores in the surface of leaves that periodically open and close under the control of a biological clock. Exercising control over this clock could be a means of conserving water. "We know that these little cells on the surface of the leaf are controlled by the clock," says McClung. "It could be that different clocks regulate it slightly differently, and we would like to find the best clock, fine-tune it, and perhaps optimize the ability to get CO₂ in without losing water."

Water figures prominently in another aspect of plant physiology. Water moves up through the stem to the leaves, involving proteins called aquaporins. "There is a big family of genes that encode aquaporins, and in Arabidopsis the circadian clock governs the expression cycles of about a third of those genes," says McClung. "That suggests there is a mechanism to actually regulate this hydraulic conductivity over time, constituting another instance where the clock is involved in water use efficiency."

New Frontiers

Together with colleagues in Wyoming, Wisconsin, and Missouri, McClung has been looking at another crop, Brassica rapa, a close relative of which is the source of canola oil. With a five-year National Science Foundation grant of more than $5 million, the group is investigating Brassica's circadian patterns, looking at inheritance and water use efficiency. "We have mapped 10 genetic regions that are associated with water use efficiency," says McClung. "We have also traced circadian parameters to most of those same areas, suggesting a link between the two. This association suggests that we could potentially use the clock to manipulate water use efficiency."

In a related project, McClung will be working with soybeans, attempting to correlate circadian period length with latitude. "If we can understand the clock, we might then manipulate the clock in ways to achieve desired goals, including water use efficiency and better yield."

Why and How?

McClung feels strongly that this sort of basic research has the potential to contribute in significant ways to food production increases. "Whether or not we achieve that increase or whether it allows us to fertilize a little less and so pollute a little less but maintain the same productivity level, anything in the net direction that is positive is going to help," he says. "We can't necessarily say exactly how it will help, but I think it's not unreasonable to think that this very basic research can have a real world impact, and one hopes it will."

Genetically Modified Organisms (GMOs)

"We will need to genetically modify our plants to control our circadian biological clocks," says Professor Rob McClung. "Every domesticated plant and animal that we have today is already genetically modified. None of them are as they are found in nature. We have manipulated their genes by selective breeding and creating hybrids."

To produce the corn we eat today, prehistoric farmers first had to find some variant that had a desirable trait, keep its seeds and plant them, repeating the process for countless generations to bring out that trait. That is selective breeding and it produced a plant whose genome was modified.

To make a tomato plant resistant to a particular disease or pest, we might find some related pest-resistant species in the wild and cross it with our garden variety tomato to produce a hybrid. Successive crosses would preserve the "tomato-ness" while selectively retaining that little bit from the wild relative that resists tomato-eating bugs.

"Along with introducing the gene or set of genes encoding resistance, we may have also brought in a whole bunch of other ill-defined genes on either side," McClung says. "We don't know the extent of it. We don't know what else is in there. While some regard this as a 'natural' approach, the unknown genetic fellow travelers could be problematic or even dangerous."

For more than 20 years, we have possessed the technology to precisely insert a single gene, making one change and only one change, producing what is known as recombinant DNA. "We are modifying genes in a much more informed way and precise way, targeting specific genes and manipulating those," he says.

"Nevertheless, there is vocal opposition to this practice, in spite of the fact that we have been doing it for decades and there is yet to be a single example of anything bad happening from that," says McClung. "It is a philosophical standpoint based on a lack of understanding. People don't understand the science and they come up with a lot of arguments against it."

The dilemma rests on timing. Conventional breeding, though imprecise and unpredictable, is a workable but lengthy process. Recombinant DNA is fast. In a world beset by overpopulation, famine and global climate change, McClung questions whether we can really afford the time to wait.

Source:

The above story is reprinted from materials provided by Dartmouth College. The original article was written by Joseph Blumberg.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Disclaimer: Views expressed in this article do not necessarily reflect those of Eagle Group or its staff.

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Link Between Obesity and Dental Health in Homeless Children Strengthened (Eagle Group- Nov 17, 2012)

Obesity and dental cavities increase and become epidemic as children living below the poverty level age.

 "It's the leading cause of chronic infections in children," said Marguerite DiMarco, associate professor at the Frances Payne Bolton School of Nursing at Case Western Reserve University.

Researchers Sheau-Huey Chiu, assistant professor, and graduate assistant Jessica L. Prokp, from the University of Akron's College of Nursing, contributed to the study.

Researchers found that as body mass index (BMI) increased with age, so do the number of cavities. These findings were published in the online Journal of Pediatric Health Care article, "Childhood obesity and dental caries in homeless children."

The study examined the physicals of 157 children, from 2 to 17 years old, at an urban homeless shelter. Most were from single-parent families headed by women with one or two children.

Obesity was calculated based on height and weight or BMI. Cavity counts included missing, filled or injured teeth. The data was originally collected for DiMarco's doctoral dissertation at Case Western Reserve nursing school.

While studies in Brazil, New Zealand, Sweden and Mexico have shown a relationship between obesity, dental health and poverty, few U.S. studies have examined how the three factors are linked.

A pediatric nurse practitioner, DiMarco said dental caries (tooth decay) and obesity outpaced such health issues as asthma among the children studied.

The findings support reports from the Centers for Disease Control and Prevention that obesity and poor oral health have doubled since 1980, raising the risk of diabetes and other health problems, as well as issues with self-esteem.

Poverty contributes to poor dental health by limiting access to nutritious food, refrigerators to preserve food and even running water in some homes, said DiMarco, who has seen dental caries as the predominant infectious disease in rural and urban children.

"Many people do not realize ," she said, "that dental caries is an infectious disease that can be transmitted from the primary caregiver and siblings to other children."

To help reduce the spread of dental infection, DiMarco reminds parents that gum disease and other oral infections can be spread by licking a child's spoon or baby bottle, or by sharing toothbrushes.

Another problem for children of poverty is access to dental care, where families lack the financial means and transportation to make and keep an appointment. And some working poor may not qualify for Ohio's Childhood Health Insurance Program, which subsidizes health and dental care reimbursements to providers.

"There are no easy solutions," DiMarco said, "especially with the homeless population."

Pediatric nurse practitioners are in a pivotal position to provide health information from birth through the teen years to prevent such health issues, DiMarco said.

Source:

The above story is reprinted from materials provided by Case Western Reserve University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1.      Sheau-Huey Chiu, Marguerite A. DiMarco, Jessica L. Prokop. Childhood Obesity and Dental Caries in Homeless Children. Journal of Pediatric Health Care, 2012; DOI: 10.1016/j.pedhc.2011.11.007

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Quick Test Speeds Search for Alzheimer's Drugs: Compound Restores Motor Function and Longevity to Fruit Flies (Eagle Group- Nov 17, 2012)

An efficient, high-volume technique for testing potential drug treatments for Alzheimer's disease uncovered an organic compound that restored motor function and longevity to fruit flies with the disease.

Flies bred to express the Alzheimer's peptide Aβ42 maintained their climbing ability longer after receiving the D737 compound (black bars) than flies that did not receive the compound (gray bars). The top panel shows flies with the standard Aβ42 gene, while the bottom panel shows flies with a disease-causing mutant gene. (Credit: Image courtesy of Angela Fortner McKoy)

Princeton University researchers report in the Journal of Biological Chemistry that they discovered an organic compound that prevented the formation of protein clumps, or aggregates, found on human brain cells afflicted by Alzheimer's disease. The researchers realized the compound's potential via a high-throughput -- meaning many materials can be examined at once -- screening process developed at Princeton that examined the ability of 65,000 molecular compounds to inhibit protein aggregation.

When administered to fruit flies bred to exhibit Alzheimer's-like symptoms, the compound -- which the researchers call D737 -- restored climbing ability and increased the flies' lifespan by several days in comparison to flies that did not receive the compound, the researchers reported.

The compound worked by stopping the accumulation of a peptide known as amyloid beta 42 (Aβ42), which disrupts cell function, is found in high quantities in Alzheimer's plaques, and is thought to initiate the disease's characteristic neural deterioration. The fruit flies were genetically engineered at the University of Cambridge to have human Aβ42 collect in their neurons. As in humans, this accumulation results in memory and mobility loss, disorientation and early death.

Senior researcher Michael Hecht, a Princeton professor of chemistry, said the findings demonstrate a quick and efficient screening method that could help in the search for a medicinal defense against Alzheimer's. Currently, he said, the disease's proliferation in an aging population has outpaced the success of efforts to develop a treatment for it.

"As the population ages, Alzheimer's is the big disease," Hecht said. "There are drugs to control symptoms, but nothing to treat the disease itself. One approach could be to control peptide aggregation as we have done, but the compounds tested so far often fail.

"Our technique would allow scientists to create an artificial genetic system, examine it with a high-throughput screen and find whether it works," Hecht said. "From that they can fish out the best results and test them in other models."

Furthermore, an effective compound such as D737 can reveal information about Aβ42's structure that can be used to formulate other treatments, said lead author Angela Fortner McKoy, a postdoctoral researcher at Rutgers University who received her Ph.D. in chemistry from Princeton in 2011. Fortner McKoy and Hecht worked with second author Jermont Chen, who earned his Ph.D. in chemistry from Princeton in 2008, and Trudi Schüpbach, the Henry Fairfield Osborn Professor of Biology.

The Princeton researchers used a screening process developed in the Hecht lab to specifically identify Aβ42 aggregation. First reported in the journal ACS Chemical Biology in 2006, the technique hinges on a fusion of Aβ42 and green fluorescent protein -- which glows under ultraviolet light and is found in animals such as jellyfish -- that is expressed in the bacteria E. coli. The fluorescent protein does not glow when Aβ42 is able to aggregate. When a compound such as D737 inhibits peptide clumping, however, the E. coli bacterium appears bright green. The efficiency of the screening system stems from the relative simplicity of attaining and working with E. coli, a standard laboratory bacterium, Hecht said.

For the current research, Hecht and his co-authors examined 65,000 randomly chosen organic compounds that Chen acquired from the Broad Institute of the Massachusetts Institute of Technology and Harvard University. The technique revealed 269 compounds that halted the buildup of Aβ42 aggregates. Of those, Fortner McKoy selected the eight most readily available for further testing. Fortner McKoy found that D737 best prevented the accumulation of Aβ42 and reduced mortality in cell cultures. In addition, the researchers found that the compound reduced the production and accumulation of reactive oxygen species, which damage cells.

The researchers then tested the compound on healthy fruit flies with no Aβ42 accumulation, as well as on flies with a regular human-form Aβ42 gene and flies with a mutant gene -- which is found in some humans with Alzheimer's -- that causes extra buildup of the peptide. For each of these three fly types, one group of flies did not receive D737 while another group was given the compound in concentrations of 2, 20 or 200 micromolar.

In the flies with regular and accelerated Aβ42 buildup, those receiving D737 lived an average of four to six days longer than similarly altered flies that were not fed the compound. The healthy fruit flies that received D737 showed no change in lifespan, demonstrating that the compound is non-toxic in fruit flies, Hecht said.

To test mobility, the researchers put 20 flies from both of the genetically altered groups into the bottom of a vial and recorded how many had climbed to the top. After 38 days, only 6 percent of untreated flies with normal Aβ42 accumulation could climb, as opposed to as many as 34 percent of the flies receiving D737.

In flies with the mutant Aβ42 gene, all those left untreated lost mobility after 27 days. Of those given the compound, however, 50 to 78 percent -- depending on the dosage -- could still climb after the same time period.

Damian Crowther, a group leader in the Department of Genetics at Cambridge who created and supplied the flies used in the Princeton research but had no active role in the work, said that D737 demonstrated a notable ability to suppress in fruit flies the same neurological, physical and mental deficits seen in humans with Alzheimer's.

"It's not common to see such a strong effect in the fly model. Of the compounds that my lab tests, which have been through rigorous in vitro screening, we see effects as good as this in only 5 to 10 percent," Crowther said. "To find that a compound administered orally is able to show beneficial effects on both of these fly phenotypes indicates that the drug can access the neurons and, once within the brain, presumably control the aggregation of amyloid beta peptides."

Crowther said the Princeton research further supports the approach of curbing the buildup of Aβ42 and related variants of the amyloid beta peptide to treat Alzheimer's. In the middle stages of accumulation, variations of the peptide can be highly toxic to neurons and kill them, he said. But the work by Hecht and his co-authors helps show that blocking amyloid-beta aggregation can be safe and potent.

"There is always a worry when looking for aggregation-blocking agents that the aggregation process may be interrupted at the wrong point," Crowther said.

"Further work should try to characterize in an in vivo system exactly where this compound halts or modifies the aggregation process," he said. "For a beneficial effect we don't need to completely block aggregation -- indeed, amyloid formation is a thermodynamically inevitable process. It could be that the compound simply modulates the aggregation process so that the most toxic intermediates are less populated."

Although the compound's success in flies would not necessarily translate to humans, Fortner McKoy said, its effectiveness illustrates that worthwhile treatment candidates can be uncovered with the Princeton screening method.

"It inhibited the peptide aggregation effectively enough so that we could see an improvement in the flies," Fortner McKoy said. "In general, a compound like this would be further developed and changes would be made to it to test its efficacy in humans. But the fly results show that it is worth testing this compound in another model."

Source:

The above story is reprinted from materials provided by Princeton University. The original article was written by Morgan Kelly.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1.      A. F. McKoy, J. Chen, T. Schupbach, M. H. Hecht. A Novel Inhibitor of Amyloid   (A ) Peptide Aggregation: FROM HIGH THROUGHPUT SCREENING TO EFFICACY IN AN ANIMAL MODEL OF ALZHEIMER DISEASE. Journal of Biological Chemistry, 2012; 287 (46): 38992 DOI: 10.1074/jbc.M112.348037 

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Smoking Affects Allergy-Relevant Stem Cells (Eagle Group- Nov 17, 2012)

Smoking is harmful to the human organism in relation to the occurrence of allergies says by a team of scientist, who has found evidence for this: Smoking affects the development of peripheral allergy-relevant stem cells in the blood. In order to present this result Dr. Irina Lehmann and Dr. Kristin Weiße chose a new scientific path: The combination of exposure analysis and stem cell research.

Stem cells are not specialised, propagate without limit and can develop to different cell types. From these the different cell and tissue types of the human organism, including the allergy-promoting eosinophil granulocytes, are differentiated. Progenitor cells, e.g. eosinophil/basophilic progenitors, which mature in the bone marrow and are then washed out into the bloodstream -- the so-called periphery -- function as a link between unspecialised stem cells and specialised tissue and organ cells. Until now, whether and to what extent environmental contaminants affect this maturation and release has not been investigated.

The UFZ team of Dr. Irina Lehmann and Dr. Kristin Weiße undertook their investigations from this point. Two facts were already known from a number of earlier studies: Firstly that the blood of allergy sufferers -- whether children or adults -- shows evidence of increased eosinophil/basophil progenitor levels. Secondly, that the occurrence of such peripheral progenitors in the blood of the umbilical cord indicates a higher risk for subsequent allergies. For the first time, the hypothesis which Dr. Kristin Weiße and Dr. Irina Lehmann developed on this basis combined this knowledge from stem cell research with the results of many years of exposure research at the UFZ. The researchers characterise their approach in the following way: "We wanted to clarify the relationship between environmental influences and the maturation and differentiation of the progenitor cells on the one hand and its contribution to the occurrence of allergies on the other hand. Specifically, we wanted to know whether the occurrence of allergy-relevant progenitor cells in the blood of infants can be changed by environmental influences."

The results of the study, based on the data collected from 60 children aged one year, were recently published in the British medical journal "Clinical & Experimental Allergy": It was found that children with skin manifestations, such as atopic dermatitis or cradle cap, have increased levels of eosinophil progenitors in their blood. In this connection, it was shown for the first time that children already afflicted show particularly sensitive reactions when exposed to environmental contaminants: The offspring of families exposed to significant levels of volatile organic compounds (VOC) at home were found to have considerably higher allergy-relevant eosinophilic/basophilic progenitor cell levels. "That VOCs, large amounts of which are released with cigarette smoke, have the greatest effect on stem cells was not entirely unexpected," explains Dr. Irina Lehmann. "Just as important, however," adds Dr. Kristin Weiße, is "that we can show that alterations in the number of stem cells as a result of harmful substances take place only in children who have already been afflicted with skin manifestations." This leads to the conclusion: There is a relationship between the genetic predisposition for a disease and environmental influences -- there are environmental and life style factors which determine whether a genetic predisposition is in fact realised or not.

Considerable logistical effort underlies this knowledge: On the one hand there is the long-term study "LiNA -- Life Style and Environmental Factors and their Influence on The Risk of Allergy" in Newborn Children, a joint project of the Helmholtz Centre for Environmental Research and the Städtisches Klinikum St. Georg in Leipzig. 622 mothers, with a total of 629 children born, were recruited for the study between 2006 and 2008. In order to also take prenatal environmental influences into account -- in contrast with earlier comparable studies of newborn children -- mothers were already included in the investigations during pregnancy and the children from the time of birth. At the same time, it was necessary to become familiar with the methods required for stem cell analysis at the laboratory of the Canadian cooperation partner, Professor Judah Denburg of the McMaster University in Hamilton and to transfer this knowledge to Germany. Dr. Kristin Weiße spent six months in Canada working in the group of Professor Denburg in order to acquire the necessary know-how and profit from the experience of the Canadian partners. Dr. Lehmann and Dr. Weiße agree that "with the subject of environmental contamination and stem cells we have established an exciting new field of research." The UFZ team is currently the only one in the world investigating this relationship with analytical precision and methodical patience. The LiNA study, in the course of which mothers and their children can be observed over several years, represents a unique basis.

Source:

The above story is reprinted from materials provided by Helmholtz Centre For Environmental Research - UFZ.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1.      K. Weisse, I. Lehmann, D. Heroux, T. Kohajda, G. Herberth, S. Röder, M. Bergen, M. Borte, J. Denburg. The LINA cohort: indoor chemical exposure, circulating eosinophil/basophil (Eo/B) progenitors and early life skin manifestations. Clinical & Experimental Allergy, 2012; 42 (9): 1337 DOI: 10.1111/j.1365-2222.2012.04024.x

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Simplifying Heart Surgery With Stretchable Electronics Devices (Eagle Group- Nov 17, 2012)

The device marks the first time stretchable electronics have been applied to a surgical process known as cardiac ablation, a milestone that could lead to simpler surgeries for arrhythmia and other heart conditions. The researchers had previously demonstrated the concept to apply stretchable electronics to heart surgery, but with this research improved the design's functionality to the point that it could be utilized in animal tests.

Cardiac ablation is a surgical technique that corrects heart rhythm irregularities by destroying specific heart tissue that triggers irregular heartbeats. The procedure is typically performed either with open-heart surgery or by inserting a series of long, flexible catheters through a vein in the patient's groin and into his heart.

Currently this catheter method requires the use of three different devices, which are inserted into the heart in succession: one to map the heart's signals and detect the problem area, a second to control positions of therapeutic actuators and their contact with the epicardium, and a third to burn the tissue away.

"Our catheter replaces all three devices previously needed for cardiac ablation therapy, making the surgery faster, simpler, and with a lower risk of complication," said Yonggang Huang, Joseph Cummings Professor of Civil and Environmental Engineering and Mechanical Engineering at McCormick.

Central to the design is a section of catheter that is printed with a thin layer of stretchable electronics. The catheter's exterior protects the electronics during its trip through the bloodstream; once inside the heart, the catheter is inflated like a balloon, exposing the electronics to a larger surface area inside the heart.

With the catheter is in place, the individual devices within can perform their specific tasks. A pressure sensor determines the pressure on the heart; an EKG sensor monitors the heart's condition during the procedure; and a temperature sensor controls the temperature so as not to damage surrounding tissue. The temperature can also be controlled during the procedure without removing the catheter.

These devices can deliver critical, high-quality information -- such as temperature, mechanical force, and blood flow -- to the surgeon in real time, and the system is designed to operate reliably without any changes in properties as the balloon inflates and deflates.

Researchers at McCormick led the efforts to design and optimize the system. (McCormick graduate student Shuodao Wang is a co-first author of the paper.) Device fabrications were done at the University of Illinois at Urbana-Champaign, and animal tests were conducted at University of Arizona Sarver Heart Center.

Other partners on this research include Seoul National University in the Republic of Korea; the University of Texas at Austin; Zhejiang University in China; the Harbin Institute of Technology in China; the Institute of High Performance Computing in Singapore; Massachusetts General Hospital; and Tufts University.

Source:

The above story is reprinted from materials provided by Northwestern University. 

 

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1.      D.-H. Kim, R. Ghaffari, N. Lu, S. Wang, S. P. Lee, H. Keum, R. D'Angelo, L. Klinker, Y. Su, C. Lu, Y.-S. Kim, A. Ameen, Y. Li, Y. Zhang, B. de Graff, Y.-Y. Hsu, Z. Liu, J. Ruskin, L. Xu, C. Lu, F. G. Omenetto, Y. Huang, M. Mansour, M. J. Slepian, J. A. Rogers. Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1205923109 

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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