RNA-interference pesticides will need special safety testing

Standard toxicity testing is inadequate to assess the safety of a new technology with potential for creating pesticides and genetically modifying crops, according to a Forum article published in the August issue of BioScience. The authors of the article, Jonathan G. Lundgren and Jian J. Duan of the USDA Agricultural Research Service, argue that pesticides and insect-resistant crops based on RNA interference, now in exploratory development, may have to be tested under elaborate procedures that assess effects on animals’ whole life cycles, rather than by methods that look for short-term toxicity.

RNA interference is a natural process that affects the level of activity of genes in animals and plants. Agricultural scientists have, however, successfully devised artificial “interfering RNAs” that  in , slowing their growth or killing them. The hope is that interfering RNAs might be applied to crops, or that crops might be genetically engineered to make interfering RNAs harmful to their pests, thus increasing crop yields.

The safety concern, as with other types of genetic modification and with pesticides generally, is that the artificial interfering RNAs will also harm desirable insects or other animals. And the way interfering RNA works means that simply testing for lethality might not detect important damaging effects. For example, an interfering RNA might have the unintended effect of suppressing the action of a gene needed for reproduction in a beneficial species. Standard laboratory testing would detect no harm, but there could be  in fields because of the effects on reproduction.

Lundgren and Duan suggest that researchers investigating the potential of interference RNA pesticides create types that are designed to be unlikely to affect non-target species. They also suggest a research program to evaluate how the chemicals move in real-life situations. If such steps are taken, Lundgren and Duan are optimistic that the “flexibility, adaptability, and demonstrated effectiveness” of RNA interference technology mean it will have “an important place in the future of pest management.”

Ecological forces structure your body's personal mix of microbes

Environmental conditions have a much stronger influence on the mix of microbes living in various parts of your body than does competition between species. Instead of excluding each other, microbes that fiercely compete for similar resources are more likely to cohabit in the same individual. This phenomenon was discovered in a recent study of the human microbiome – the vast collection of our resident bacteria, , and other tiny organisms. The findings were published on July 15, in the early online edition of PNAS, the Proceedings of the National Academy of Sciences.

The study is one of the early steps toward a major goal of Dr. Elhanan Borenstein, the lead scientist on the project. His team hopes to build a  of the human microbiome as a tool to study how  can change this massive , to identify settings that promote beneficial microbiomes, and to design clinical interventions to treat currently hard-to-manage problems. For example, diet or  might be developed to manipulate the microbiome to achieve desired outcomes, such as fixing a chronic digestive inflammation.

“The large communities of  residing on and inside us are critical to our state of health or illness,” said Borenstein, a University of Washington assistant professor of  and computer science and engineering, who conducted the study with his graduate student, Roie Levy.

He explained why medical scientists are interested in the forces that structure our distinctive assemblies of microbes: This knowledge may show clinicians how to restore a more normal pattern in patients whose microbiome has been disrupted by illness, infection, toxins or injury. It can also help them better understand how disease states, such as obesity or  are reflected in and affected by the microbiome.

Ecological forces structure your body’s personal mix of microbes

“Through major genetics studies,” Borenstein noted, “scientists have made valuable progress in gathering information on the species composition of the human microbiome in health and disease.” He added that little is known, however, about the underlying ecology that determines the make-up of the human microbiome. Compositional studies alone do not explain how the various  interact, cooperate or compete to form, maintain or alter their populations.

Borenstein and his team use a systems biology approach and apply sophisticated computer modeling to understand the structure, function, and dynamics of the microbiome. In the current study, for example, they utilized genomic information from hundreds of microbial species commonly found in humans to create computer models of nutrient and energy metabolism. From these models they predicted the nutrients each species requires and the interactions between microbes. Specifically, they were able to estimate how strongly each pair of microbes competes over available nutrients or cooperates in producing necessary compounds. They then compared these predicted interactions to the abundances of microbial species across samples from different individuals.

In this way they learned that species tend to co-exist more frequently with other species with which they strongly compete for their needs, instead of winners overtaking losers. Ecologists, including those who study bigger-size plants and animals, call this habitat filtering. It means that species with similar requirements for life are selected by the environment and co-occur in the same location. Habitat filtering contrasts with another theory, species assortment, in which organisms seeking nearly identical resources clash until a victorious species triumphs.

Borenstein noted, “Species interaction plays a role, but the environment exerts a stronger effect.”

He also indicated that even when his research team corrected for the presence of obesity, inflammatory bowel disease and other factors, they still saw the previously observed pattern of competitor microbes staying together.

This suggests, he explained, that the lines along which species are filtered and microbiomes are assembled are not fully defined by major physiological abnormalities in a patient, but might take place at a finer scale.

Explore further: Your body’s microbiome has a unique ‘fingerprint’

CELLULAR COMMUNICATION DISCOVERED IN THE BRAIN – NEW INSIDES

Researchers at Johannes Gutenberg University Mainz (JGU) have discovered a new form of communication between different cell types in the brain. Nerve cells interact with neighboring glial cells, which results in a transfer of protein and genetic information. Nerve cells are thus protected against stressful growth conditions. The study undertaken by the Mainz-based cell biologists shows how reciprocal communication between the different cell types contributes to neuronal integrity. Their results have been recently published in the journalPLOS Biology.

Brain function is determined by the communication between electrically excitable neurons and the surrounding, which perform many tasks in the brain. Oligodendrocytes are a type of glial cell and these form an insulating myelin sheath around the  of neurons. In addition to providing this protective insulation, oligodendrocytes also help sustain neurons in other ways that are not yet fully understood. If this support becomes unavailable, axons can die off. This is what happens in many forms of myelin disorders, such as multiple sclerosis, and it results in a permanent loss of neuron impulse transmission.

Like other types of cell, oligodendrocytes also secrete small vesicles. In addition to lipids and proteins, these membrane-enclosed transport packages also contain , in other words, genetic information. In their study, Carsten Frühbeis, Dominik Fröhlich, and Wen Ping Kuo of the Institute of Molecular Cell Biology at Johannes Gutenberg University Mainz found that oligodendrocytes release nano-vesicles known as ‘exosomes’ in response to neuronal signals. These exosomes are taken up by the neurons and their cargo can then be used for neuronal metabolism. “This works on a kind of ‘delivery on call’ principle,” explained Dr. Eva-Maria Krämer-Albers, who is leading the current study. “We believe that what are being delivered are ‘care packages’ that are sent by the oligodendrocytes to neurons.”

While studying cell cultures, the research group discovered that the release of exosomes is triggered by the neurotransmitter glutamate. By means of labeling them with reporter enzymes, the researchers were able to elegantly demonstrate that the small vesicles are absorbed into the interior of the neurons. “The entire package of substances, including the genetic information, is apparently utilized by the neurons,” said Krämer-Albers. If neurons are subjected to stress, cells that have been aided with ‘care packages’ subsequently recover. “This maintenance contributes to the protection of the neurons and probably also leads to de novo synthesis of proteins,” stated Carsten Frühbeis and Dominik Fröhlich. Among the substances that are present in the exosomes and are channeled to the are, for instance, protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes which counter oxidative stress.

The study has demonstrated that exosomes from oligodendrocytes participate in a previously unknown form of bidirectional cell communication that could play a significant role in the long-term preservation of nerve fibers. “An interaction like this, in which an entire package of substances including  is exchanged between cells of the nervous system, has not previously been observed”, stated Krämer-Albers, summarizing the results. “Exosomes are thus similar to viruses in certain respects, with the major difference that they do not inflict damage on the target cells but are instead beneficial.” In the future, the researchers hope to develop exosomes as possible ‘cure’ packages that could be used in the treatment of nerve disorders.

New mode of cellular communication discovered in the brainNew mode of cellular communication discovered in the brain

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