Carnivorous plant packs big wonders into tiny genome

Light micrograph of the bladder of Utricularia gibba, the humped bladderwort plant (color added).

Great, wonderful, wacky things can come in small genomic packages.

That's one lesson to be learned from the carnivorous bladderwort, a plant whose tiny genome turns out to be a jewel box full of evolutionary treasures.

Called Utricularia gibba by scientists, the bladderwort is a marvel of nature. It lives in an aquatic environment. It has no recognizable roots. It boasts floating, thread-like branches, along with miniature traps that use vacuum pressure to capture prey.

A new study in the scientific journal Molecular Biology and Evolution breaks down the plant's genetic makeup, and finds a fascinating story.

According to the research, the bladderwort houses more genes than several well-known plant species, such as grape, coffee or papaya -- despite having a much smaller genome.

This incredibly compact architecture results from a history of "rampant" DNA deletion in which the plant added and then eliminated genetic material at a very fast pace, says University at Buffalo Professor of Biological Sciences Victor Albert, who led the study.

"The story is that we can see that throughout its history, the bladderwort has habitually gained and shed oodles of DNA," he says.

"With a shrunken genome," he adds, "we might expect to see what I would call a minimal DNA complement: a plant that has relatively few genes -- only the ones needed to make a simple plant. But that's not what we see."

A unique and elaborate genetic architecture

In contrast to the minimalist plant theory, Albert and his colleagues found that U. gibba has more genes than some plants with larger genomes, including grape, as already noted, and Arabidopsis, a commonly studied flower.

A comparison with the grape genome shows U. gibba's genetic opulence clearly: The bladderwort genome, holding roughly 80 million base pairs of DNA, is six times smaller than the grape's. And yet, the bladderwort is the species that has more genes: some 28,500 of them, compared to about 26,300 for the grape.

U. gibba is particularly rich in genes that may facilitate carnivory -- specifically, those that enable the plant to create enzymes similar to papain, which helps break down meat fibers. The bladderwort is also rich in genes linked to the biosynthesis of cell walls, an important task for aquatic species that must keep water at bay.

"When you have the kind of rampant DNA deletion that we see in the bladderwort, genes that are less important or redundant are easily lost," Albert says. "The genes that remain -- and their functions -- are the ones that were able to withstand this deletion pressure, so the selective advantage of having these genes must be pretty high.

"Accordingly, we found a number of genetic enhancements, like the meat-dissolving enzymes, that make Utricularia distinct from other species."

Much of the DNA the bladderwort deleted over time was noncoding "junk DNA" that contains no genes, Albert says.

High gene turnover

The study included partners from UB, the Universitat de Barcelona in Spain, the Laboratorio Nacional de Genómica para la Biodiversidad (LANGEBIO) in Mexico and the Instituto de Ecología in Mexico.

To determine how the bladderwort evolved its current genetic structure, the team compared the plant to four related species. What they uncovered was a pattern of rapid DNA alteration.

As Albert explains, "When you look at the bladderwort's history, it's shedding genes all the time, but it's also gaining them at an appreciable enough rate, permitting it to stay alive and produce appropriate adaptations for its unique environmental niche."

In the realm of DNA gain, the study found that U. gibba has undergone three duplication events in which its entire genome was replicated, giving it redundant copies of every gene.

This fast-paced gene gain was balanced out by swift deletion. Evidence for this phenomenon comes from the fact that the plant has a tiny genome despite its history of genetic duplication. In addition, the plant houses a high percentage of genes that don't have close relatives within the genome, which suggests the plant quickly deleted redundant DNA acquired through duplication events.

The study builds on the work of Albert and other team members, who reported in the journal Nature in 2013 that the bladderwort's genome was comprised almost entirely of useful, functional genes and their controlling elements, in contrast to species like humans, whose genomes are more than 90 percent "junk DNA."

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Retracing the roots of fungal symbioses

Mycorrhizal fungi include some of the most conspicuous forest mushrooms, such as the iconic fly agaric (Amanita muscaria), of the fungi sequenced for this project.

With apologies to the poet John Donne, and based on recent work from the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science user facility, it can be said that no plant is an island, entire of itself. Unseen by the human eye, plants interact with many species of fungi and other microbes in the surrounding environment, and these exchanges can impact the plant's health and tolerance to stressors such as drought or disease, as well as the global carbon cycle.

Mycorrhizal fungi live in the roots of host plants, where they exchange sugars that plants produce by photosynthesis for mineral nutrients that fungi absorb from the soil. They include some of the most conspicuous forest mushrooms, including the iconic, flaming red "fly agaric," Amanita muscaria, and are of interest to bioenergy researchers, because they play roles in maintaining the health of candidate feedstock crop trees. Recent studies indicate that mycorrhizal fungi also play a significant role in belowground carbon sequestration, which may mitigate the effects of anthropogenic CO2 emissions.

To understand the basis for fungal symbiotic relationships with plants, a team of DOE JGI researchers led by Igor Grigoriev and longtime collaborators at the French National Institute for Agricultural Research (INRA) and Clark University conducted the first broad, comparative phylogenomic analysis of mycorrhizal fungi, drawing on 49 fungal genomes, 18 of which were sequenced for this study. The 18 new fungal sequences included 13 mycorrhizal genomes, from ectomycorrhizal fungi that penetrate the host roots, and including species that comingle with orchid and heathland (which include blueberry, heather, and heath) plant roots. In the February 23, 2015 online edition of Nature Genetics, these researchers describe how the comparative analyses of these genomes allowed them to track the evolution of mycorrhizal fungi. The results help researchers understand how plants and fungi developed symbiotic relationships, and how the mutualistic association provides host plants with beneficial traits for environmental adaptation.

Starting with previously sequenced mycorrhizal fungi

"Mycorrhizal symbioses are highly complex, but analyses of the 49 genomes indicate that they have evolved independently in many fungal lineages," said INRA's Francis Martin, one of the study's senior authors. To understand the genetic shifts underlying the repeated origins of mycorrhizal lifestyles, the researchers focused on enzymes that degrade plant cell walls from 16 gene families associated with plant cell wall degradation. They took their cue from the first sequenced ectomycorrhizal fungus, Laccaria bicolor and the first sequenced arbuscular mycorrhizal fungus Rhizophagus irregularis- all work done at the DOE JGI-which illuminates the origins and evolution of these enzymes, knowledge to be applied in collaboration for improving biomass breakdown for biofuels production.

Through molecular clock analyses, which combine genome-scale molecular data with fossil calibrations, the team could work backwards to estimate when saprotrophic and mutualistic lineages last shared common ancestors based on the amount of divergence.

The analyses of the fungal genomes and fossils suggested that in comparison to brown rot fungi and white rot fungi that evolved over 300 million years ago, ectomycorrhizal fungi emerged fairly recently from several species and then spread out across lineages less than 200 million years ago. The team also found that up to 40 percent of the symbiosis-induced genes were restricted to a single mycorrhizal species.

Fungi evolving to break down plant cell walls

David Hibbett of Clark University, another of the study's senior authors, compared the work to a previous collaboration with the DOE JGI detailed in Science to trace the evolution of white rot fungi, which are capable of breaking down cellulose, hemicellulose and lignin in plants. Prior to the emergence of white rot fungi hundreds of millions of years ago, fungi were not capable of breaking down lignin, and the undecayed plant mass became the basis of large coal deposits.

"Together these studies tell a story about how mushroom-forming fungi evolved a complex mechanism for breakdown of plant cell walls in 'white rot' and then cast it aside following the evolution of mycorrhizal associations, as well as the alternative decay mechanism of 'brown rot,'" Hibbett said. "The other major part of the story is that in mycorrhizal lineages there is a huge turnover in genes that are upregulated in the symbiosis-many of these have no homologs in even closely related species, suggesting that the evolution of the symbiosis is associated with massive genetic innovation."

Martin chimed in: "Many of these genes are likely used to control plant immunity during the massive colonization of root tissues by the fungus."

DOE JGI's Igor Grigoriev also pointed out, "This first large-scale study of mycorrhizal genomics is also the first step in both broader and deeper exploration of mycorrhizal diversity, their interactions with host plans, and roles in forest ecosystems using genomics tools, which are the focus areas for the JGI Fungal Genomics Program."

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Bacteria network for food

Electron micrograph of genetically modified Acinetobacter baylyi and Escherichia coli strains. The bacteria exchange amino acids via nanotubes (i.e. tube-like connections between cells).

It is well-known that bacteria can support each others' growth and exchange nutrients. Scientists at the Max Planck Institute for Chemical Ecology in Jena, Germany, and their colleagues at the universities of Jena, Kaiserslautern, and Heidelberg, however, have now discovered a new way of how bacteria can achieve this nutritional exchange. They found that some bacteria can form nanotubular structures between single cells that enable a direct exchange of nutrients (Nature Communications, February 2015).

Bacteria usually live in species-rich communities and frequently exchange nutrients and other metabolites. Until now, it was unclear whether microorganisms exchange metabolites exclusively by releasing them into the surrounding environment or whether they also use direct connections between cells for this purpose. Scientists from the Research Group Experimental Ecology and Evolution at the Max Planck Institute for Chemical Ecology in Jena, Germany addressed this question using the soil bacterium Acinetobacter baylyi and the gut microbe Escherichia coli. By experimentally deleting bacterial genes from the genome of both species, the scientists generated mutants that were no longer able to produce certain amino acids, yet produced increased amounts of others.

In co-culture, both bacterial strains were able to cross-feed each other, thereby compensating the experimentally induced deficiencies (see also our press release "Division of Labor in the Test Tube − Bacteria grow faster if they feed each other," December 2, 2013). However, separating the two bacterial strains with a filter that allowed free passage of amino acids, yet prevented a direct contact between cells, abolished growth of both strains. "This experiment showed that a direct contact between cells was required for the nutrient exchange to occur," explains Samay Pande, who recently obtained his PhD at the Max Planck Institute in Jena on this research project and now started a postdoc at the ETH Zürich.

Observing the co-culture under the electron microscope revealed structures that formed between bacterial strains, which functioned as nanotubes and enabled the exchange of nutrients between cells. Especially remarkable, however, was the fact that only the gut microbe Escherichia coli was capable of forming these structures and connecting to Acinetobacter baylyi or other E. coli cells. "The major difference between both species is certainly that E. coli is able to actively move in liquid media, whereas A. baylyi is immotile. It may thus be possible that swimming is required for E. coli to find suitable partners and connect to them via nanotubes," explains Christian Kost, head of the Research Group Experimental Ecology and Evolution, which is funded by the Volkswagen Foundation.

"A lack of amino acids triggered the formation of nanotubes. Deleting a gene, which is involved in the production of a certain amino acid, caused the resulting bacteria to connect to other bacterial cells and − in this way − compensate their nutritional deficiency. However, nanotubes did not form when the required amino acids were supplemented to the growth medium, indicating that the formation of these structures obviously depends on how 'hungry' a cell is," the scientist summarizes the results.

Cells that specialize on particular biochemical processes and thereby divide their labor can be advantageous for bacterial communities: Resources can be used more economically, thus enhancing growth and efficiency. Whether the formation of nanotubes exclusively serves the mutual exchange of nutrients or whether some bacterial species also parasitize other bacterial cells in this way will be subject to further investigation. Moreover, it remains unclear whether bacteria can actively choose the cells to which they attach. After all, such tubular connections also pose a potential risk, because the partner on the other side of the tube could also provide harmful substances.

"To me, the most exciting question that remains to be answered is whether bacteria are in fact unicellular and relatively simply structured organisms or whether we are actually looking at some other type of multicellularity, in which bacteria increase their complexity by attaching to each other and combining their biochemical abilities," Christian Kost summarizes. His research focuses mainly on the question why organisms cooperate with each other. Using bacterial communities as experimentally tractable model systems will help to explain why so many organisms have developed a cooperative lifestyle in the course of their evolution.

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Yellow Sugarcane Aphid Detected in Continental Europe

Researchers from the UAB and CREAF and from the University of León have discovered this species in Tarragona and Girona, which probably arrived from Northern Africa. It is also the first time that this species is found in Continental Europe.

Aphids are a kind of insects typically living on the aerial part of plants, feeding on the sap that flows through the phloem of plants with a specialized buccal apparatus. That is why they often behave as a pest in agricultural crops.

Recently, Carlos Hernández-Castellano, student of the MSc in Terrestrial Ecology at the Universitat Autònoma de Barcelona and research collaborator of the Centre for Ecological Research and Forestry Applications, and Nicolás Pérez Hidalgo, researcher from the University of León, discovered a new aphid species for the European Continent, in La Selva del Camp (province of Tarragona) and Blanes (province of Girona) (NE Spain).

This aphid, called Sipha flava, is native to North America, although it has achieved to expand throughout South and Central America. In these regions it is known as "the yellow sugarcane aphid," and is an important pest of this crop, where it feeds on the plant and acts as a virus vector, leading to yield reduction.

The researchers contemplate the possibility that the species has reached Continental Europe from the Southern Iberian Peninsula as a result of sugarcane crop expansion in northern Africa.

"This crop is rather marginal in European Continent, so Sipha flava is not expected to become a sugarcane pest in this zone. However, we know that it feeds on several species from the same family, in this case grasses, and it is unknown to what extent the aphid could represent a threat to these kinds of crops in Europe, such as rice or corn," Carlos Hernández-Castellano explains. Therefore, a distribution map of this species in Europe is needed in order to evaluate its potential pest behaviour, implementing the principle of precaution."

In addition to the new species for the European Continent, researchers also discovered the first case in Eurasia and North Africa of an aphid feeding on a plant from the genus Hyparrhenia (also from the grass family), and also contributed with the first evidences that this aphid is attended by ants -- ants and aphids tend to establish mutualistic relationships, in which ants offer protection in exchange for honeydew excreted by the aphids.

This discovery, researchers say, highlights the increasing threat of invasive species, a booming phenomenon caused by globalisation, leading not only to agricultural issues but also rising as the second cause of biodiversity loss in the world, just after habitat destruction in importance.

Therefore they point out that, although the finding supposes an increase in the diversity knowledge of this aphid genera -- to date just 10 species of this genus were known in Europe, and only 3 in the Iberian Peninsula -- the alert message is clear.

The discovery was made during a sampling campaign which aimed to study the insect trophic web of an organic citrus grove. The work was carried out in the context of Fauna Iberica Project, which aims to catalogue and to establish the distribution of the whole animal diversity in the Iberian Peninsula in order to guarantee its conservation.

The report is available online at: http://redia.it/images/stories/pdf2014/Redia_97_2014_16%20Hernandez%20%20et%20al__.pdf

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New products from bark to replace fossil compounds: Adhesives and insulating foams from softwood bark tannins

In collaboration with its partners, VTT developed tannin extraction from softwood bark as part of an ERA-NET project. At least 130 kg of crude tannin powder can be produced from one tonne of dry wood bark, still leaving 87% of the original bark mass available for incineration. In Finland, tannin could replace, in particular, fossil-based phenols in adhesives used in the wood products industry.

Hundreds of tonnes of tannin is produced from wood materials and wood bark for the needs of leather, beverage and animal feed industry in South America and South Africa in particular. However, the supply of the main sources of tannin, acacia and quebracho trees, is not sufficient to satisfy the increasing industrial demand for tannin.

In industrial use, tannin could be used to replace fossil chemicals in adhesives and insulating foams. In Finland, softwood bark tannins would be well suited for adhesive production for the manufacturing of wood products at sawmills. It could also enhance the fire resistance of insulating foams.

As part of the international ERA-NET project, VTT Technical Research Centre of Finland Ltd developed, in collaboration with its partners, a tannin extraction process from bark material generated as a by-product in the paper and wood industry to give added value to the fraction currently used for incineration.

Extraction and drying produce 130 kg of tannin powder from one tonne of wood bark

The extraction process is quite simple: tannin can be extracted from bark using hot water, after which the extract is dried into a powder. Drying the water extract into powder may not be necessary if the tannin is extracted near the site where glued wood products are manufactured. One tonne of dry wood bark yields at least 130 kg of tannin powder, leaving 87% of the original bark mass available for incineration.

The tannin extracted from present raw material sources is relatively pure. Extract from spruce bark, however, also contains other compounds, carbohydrates in particular, which limits the use of crude tannin. Yet, it may be possible to develop extraction and extract purification technologies for different end uses. The market price per kilo of tannin extracted from present raw material sources is approximately 1-2 euros. The market price per kilo of phenol is has varied recently from 0.8 to 1.4 euros.

VTT part of the three-year BioFoamBark project (2012−2014) was financed by Tekes -- the Finnish Funding Agency for Innovation , Savanaho Ltd, Finnish Wood Research Oy and Chemigate Ltd. Other project partners were University of Freiburg, University of Ljubljana, Université de Lorraine, University of Santiago de Compostela, Fraunhofer Institute of Solar Energy Systems ISE, Nova-Institut GmbH and Ledoga Srl.

Multi-purpose tannin

One of tannin's special properties is its ability to precipitate proteins and for this reason it has been used for tanning leather for thousands of years. This natural polyphenol is also known as a natural or added ingredient in red wine, where it clarifies the liquid and improves its shelf life and taste. Tannin is also added to certain feed products. For example, it enhances cattle's ability to take advantage of proteins contained in feed in its metabolic processes.

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Virus-cutting enzyme helps bacteria remember a threat

Microbial memory: CRISPR systems allow bacteria to adapt to new viral threats. Above, Staphylococcus aureus microbes lacking a CRISPR system are killed off by the bacteria-attacking virus ?NM4. This plate approximates the concentration of virus particles used in the recent experiments.

Bacteria may not have brains, but they do have memories, at least when it comes to viruses that attack them. Many bacteria have a molecular immune system which allows these microbes to capture and retain pieces of viral DNA that they have encountered in the past, in order to recognize and destroy it when it shows up again.

Research at Rockefeller University described in Nature offers new insight into the mysterious process by which this system works to encode viral DNA in a microbe's genome for later use as guides for virus-cutting enzymes.

"Microbes, like vertebrates, have immune systems capable of adapting to new threats. Cas9, one enzyme employed by these systems, uses immunological memories to guide cuts to viral genetic code. However, very little is known about how these memories are acquired in the first place," says Assistant Professor Luciano Marraffini, head of the Laboratory of Bacteriology. "Our work shows that Cas9 also directs the formation of these memories among certain bacteria."

These memories are embedded in the bacterial equivalent of an adaptive immune system capable of discerning helpful from harmful viruses called a CRISPR (clustered regularly interspaced short palindromic repeats) system. It works by altering the bacterium's genome, adding short viral sequences called spacers in between the repeating DNA sequences. These spacers form the memories of past invaders. They serve as guides for enzymes encoded by CRISPR-associated genes (Cas), which seek out and destroy those same viruses should they attempt to infect the bacterium again.

Cas9's ability to make precision cuts within a genome -- viral or otherwise -- has caught the attention of researchers who now use it to alter cells' genetics for experimental or therapeutic purposes. But it is still not well understood just how this CRISPR system works in its native bacteria.

Some evidence suggested that other Cas enzymes managed the memory-making process on their own, without Cas9. But because of the way Cas9 goes about identifying the site at which to make a cut, the researchers, including co-first authors Robert Heler, a graduate student, and Poulami Samai, a postdoc in the lab, suspected a role for Cas9 in memory making.

In addition to matching its CRISPR guide sequence up with the DNA of the virus, Cas9 needs to find a second cue nearby: a PAM (protospacer adjacent motif) sequence in the viral DNA. This is a crucial step, since it is the absence of a PAM sequence that prevents Cas9 from attacking the bacterium's own memory-containing DNA.

"Because Cas9 must recognize a PAM sequence before cutting the viral DNA, it made sense to us that Cas9 would also recognize the PAM sequence when the system is forming a memory of its first encounter with a virus," Heler says. "This is a new and unexpected role for Cas9."

To test their hypothesis, Heler swapped the Cas9 enzymes between the immune systems of Streptococcus pyogenes and Streptococcus thermophilus, each of which recognizes a different PAM sequence. As a result, the PAM sequences followed, swapping between the two bugs -- evidence that Cas9 is responsible for identifying the PAM during memory formation. In another experiment, he altered the part of Cas9 that binds to the PAM sequence, and found the microbes then began acquiring the target viral sequences randomly, making them unusable.

Samai, meanwhile, looked at the relationship between Cas9 and three other Cas enzymes: Cas1, Cas2 and Csn2. Components of the same CRISPR system, these enzymes were already suspected to play a role in memory making without help from Cas9.

Samai expressed these enzymes together, then tagged each one and attempted to purify it. But each time, the other three came out as well. "This indicates there is some kind of interaction between the four; most likely they form a complex during the acquisition of memory," she says.

"Because of its importance to biotechnology, Cas9's has attracted a great deal of interest for its action targeting and cleaving viral genomes. Our work reveals an overlooked role for Cas9: forming the memories that make adaptive immunity possible for bacteria," Marraffini says.

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Newborn neurons in adult brain may help us adapt to environment

Neurons (stock image). "New neurons may serve as a means to fine-tune the hippocampus to the predicted environment," Opendak says. "In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain.

The discovery that the human brain continues to produce new neurons in adulthood challenged a major dogma in the field of neuroscience, but the role of these neurons in behavior and cognition is still not clear. In a review article published by Cell Press February 21st in Trends in Cognitive Sciences, Maya Opendak and Elizabeth Gould of Princeton University synthesize the vast literature on this topic, reviewing environmental factors that influence the birth of new neurons in the adult hippocampus, a region of the brain that plays an important role in memory and learning.

The authors discuss how the birth of such neurons may help animals and humans adapt to their current environment and circumstances in a complex and changing world. They advocate for testing these ideas using naturalistic designs, such as allowing laboratory rodents to live in more natural social burrow settings and observing how circumstances such as social status influence the rate at which new neurons are born.

"New neurons may serve as a means to fine-tune the hippocampus to the predicted environment," Opendak says. "In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain. However, more naturalistic experimental conditions may be a necessary step toward understanding the adaptive significance of neurons born in the adult brain."

In recent years, it has become increasingly clear that environmental influences have a profound effect on the adult brain in a wide range of mammalian species. Stressful experiences, such as restraint, social defeat, exposure to predator odors, inescapable foot shock, and sleep deprivation, have been shown to decrease the number of new neurons in the hippocampus. By contrast, more rewarding experiences, such as physical exercise and mating, tend to increase the production of new neurons in the hippocampus.

The birth of new neurons in adulthood may have important behavioral and cognitive consequences. Stress-induced suppression of adult neurogenesis has been associated with impaired performance on hippocampus-dependent cognitive tasks, such as spatial navigation learning and object memory. Stressful experiences have also been shown to increase anxiety-like behaviors that are associated with the hippocampus. In contrast, rewarding experiences are associated with reduced anxiety-like behavior and improved performance on cognitive tasks involving the hippocampus.

Although scientists generally agree that our day-to-day actions change our brains even in adulthood, there is some disagreement on the adaptive significance of new neurons. For instance, the literature presents mixed findings on whether new neurons generated under a specific experimental condition are geared toward the recognition of that particular experience or if they provide a more naive pool of new neurons that enable environmental adaptation in the future.

Gould and her collaborators recently proposed that stress-induced decreases in new neuron formation might improve the chances of survival by increasing anxiety and inhibiting exploration, thereby prioritizing safety and avoidant behavior at the expense of performing optimally on cognitive tasks. On the other hand, reward-induced increases in new neuron number may reduce anxiety and facilitate exploration and learning, leading to greater reproductive success.

"Because the past is often the best predictor of the future, a stress-modeled brain may facilitate adaptive responses to life in a stressful environment, whereas a reward-modeled brain may do the same but for life in a low-stress, high-reward environment," says Gould, a professor of psychology and neuroscience at Princeton University.

However, when aversive experiences far outnumber rewarding ones in both quantity and intensity, the system may reach a breaking point and produce a maladaptive outcome. For example, repeated stress produces continued reduction in the birth of new neurons, and ultimately the emergence of heightened anxiety and depressive-like symptoms.

"Such a scenario could represent processes that are engaged under pathological conditions and may be somewhat akin to what humans experience when exposed to repeated traumatic stress," Opendak says.

Because many studies that investigate adult neurogenesis use controlled laboratory conditions, the relevance of the findings to real-world circumstances remains unclear. The use of a visible burrow system--a structure consisting of tubes, chambers, and an open field--has allowed researchers to recreate the conditions that allow for the production of dominance hierarchies that rats naturally form in the wild, replicating the stressors, rewards, and cognitive processes that accompany this social lifestyle.

"This more realistic setting has revealed individual differences in adult neurogenesis, with more new neurons produced in dominant versus subordinate male rats," Gould says. "Taking findings from laboratory animals to the next level by exploring complex social interactions in settings that maximize individual variability, a hallmark of the human experience, is likely to be especially illuminating."

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Breastfeeding, other factors help shape immune system early in life

Henry Ford Hospital researchers say that breastfeeding and other factors influence a baby's immune system development and susceptibility to allergies and asthma by what's in their gut.

The striking findings from a series of studies further advance the so-called hygiene hypothesis theory that early childhood exposure to microorganisms affects the immune system's development and onset of allergies, says Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford's Department of Public Health Sciences and principal research investigator.

The gut microbiome is the collection of microorganisms in the gastrointestional, or GI, tract, and the human body has billions of these microbes. The GI tract contains what scientists often call a bacterial ecosystem. The gut microbiome is known to play an important role in immune system development, and is thought to contribute to a host of diseases like obesity, autoimmune diseases, circulating disorders and pediatric allergies and infection.

"For years now, we've always thought that a sterile environment was not good for babies. Our research shows why. Exposure to these microorganisms, or bacteria, in the first few months after birth actually help stimulate the immune system," Dr. Johnson says.

"The immune system is designed to be exposed to bacteria on a grand scale. If you minimize those exposures, the immune system won't develop optimally."

The studies are being presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology in Houston.

The findings come from Henry Ford's long-running Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), funded by the National Institute of Allergy and Infectious Diseases, that is exploring the role of environmental factors and measuring biological markers to understand how allergies and asthma develop early in life.

In six separate studies, researchers sought to evaluate whether breastfeeding and maternal and birth factors had any effect on a baby's gut microbiome and allergic and asthma outcomes. Using data collected from the WHEALS birth cohort, researchers analyzed stool samples from infants taken at one month and six months after birth. They also looked at whether the gut microbiome impacted the development of regulatory T-cells, or Treg, which are known to regulate the immune system. Highlights:

• Breastfed babies at one month and six months had distinct microbiome compositions compared to non-breastfed babies. These distinct compositions may influence immune system development. • Breastfed babies at one month were at decreased risk of developing allergies to pets. • Asthmatic children who had nighttime coughing or flare-ups had a distinct microbiome composition during the first year of life. • For the first time, gut microbiome composition was shown to be associated with increasing Treg cells.

Researchers found that a baby's gut microbiome patterns vary by:
• A mother's race/ethnicity.
• A baby's gestational age at birth.
• Prenatal and postnatal exposure to tobacco smoke.
• Caesarean section versus vaginal delivery.
• Presence of pets in the home.

Dr. Johnson and her team, which includes researchers at George Regents University, University of California-San Francisco and University of Michigan, have been at the forefront of research investigating how allergies develop in early life and the role of environmental factors. Henry Ford's landmark 2002 study found exposure to dogs or cats in the first year of a baby's life reduced their risk for allergies.

"The research is telling us that exposure to a higher and more diverse burden of environmental bacteria and specific patterns of gut bacteria appear to boost the immune system's protection against allergies and asthma," Dr. Johnson says.

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Popular YouTube videos drown viewers with positive portrayals of drunkenness

The 70 most popular videos depicting drunkenness on YouTube account for more than 330 million views, with little portrayal of the negative outcomes of excessive alcohol consumption, according to an analysis led by the University of Pittsburgh Center for Research on Media, Technology, and Health (CRMTH).

The popularity of such videos on YouTube could be an opportunity for public health interventions aimed at educating teenagers and young adults of the negative consequences of intoxication, the researchers suggest in an article published in today's issue of the journal Alcoholism: Clinical and Experimental Research.

"There has been little research examining Internet-based, alcohol-related messaging," said lead author Brian A. Primack, M.D., Ph.D., director of CRMTH and assistant vice chancellor for health and society in Pitt's Schools of the Health Sciences. "While we know that some viewers may be savvy enough to skeptically view music videos or advertisements portraying intoxication as fun, those same viewers may be less cynical when viewing user-generated YouTube videos portraying humorous and socially rewarding escapades of a group of intoxicated peers."

Dr. Primack's team mined YouTube for five terms synonymous with alcohol intoxication -- drunk, buzzed, hammered, tipsy and trashed -- winnowing their findings down to the most relevant.

There were a total of 333,246,875 views for all 70 videos combined.

• Humor was juxtaposed with alcohol use in 79 percent of the videos.
• Motor vehicle use was present in 24 percent.
• Although 86 percent of the videos showed active intoxication, only 7 percent contained references to alcohol dependence.
• An average of 23.2 "likes" were registered for every "dislike."
• While 89 percent of the videos involved males, only 49 percent involved females.
• A specific brand of alcohol was referenced in 44 percent of the videos.

"This is the first comprehensive attempt to analyze YouTube data on intoxication, and these statistics should be valuable in guiding interventions," said Dr. Primack, also a practicing physician. "For example, we know that men tend to report more frequent binge drinking than women and that alcohol use is perceived as more socially acceptable for men. Because they are portrayed more frequently in YouTube videos, it may be useful to target men with future interventions debunking alcohol-related myths propagated on social media."

Dr. Primack found it concerning that nearly half the videos contained specific brand references. While this could indicate industry influence, the researchers did not note any clear indication of intentional advertising. Past research has linked exposure to brand references in popular media to encouraging alcohol consumption.

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A lower IQ has been linked to greater and riskier drinking among young adult men

Although several studies have shown an association between intelligence and various health-related outcomes, the research on cognitive abilities and alcohol-related problems has been inconsistent. A new study of the association between IQ-test results and drinking, measured as both total intake and pattern of use, has found that a lower IQ is clearly associated with greater and riskier drinking among young adult men, although their poor performance on the IQ-test may also be linked to other disadvantages.

Results will be published in the March 2015 online-only issue of Alcoholism: Clinical & Experimental Research.

"Previous results in this area have been inconsistent," said Sara Sjölund, a doctoral student at the Karolinska Institutet in Stockholm, Sweden as well as corresponding author for the study. "In two studies where the CAGE questionnaire -- a method of screening for alcoholism -- was used, a higher cognitive ability was found to be associated with a higher risk for drinking problems. Conversely, less risk has been found when looking at outcomes such as, for example, International Classification of Diseases diagnoses of alcoholism, alcohol abuse, and dependence."

"In this study of a general population, intelligence probably comes before the behavior, in this case, alcohol consumption and a pattern of drinking in late adolescence," said Daniel Falkstedt, assistant professor in the department of public health sciences at Karolinska Institutet. "It could be the other way around for a minority of individuals, that is, when exposure to alcohol has led to cognitive impairment, but this is less likely to be found among young persons of course."

Sjölund and her colleagues analyzed data collected from 49,321 Swedish males born during 1949 to 1951 and who were conscripted for Swedish military service from 1969 to 1971. IQ results were available from tests performed at conscription, and questionnaires also given at conscription provided data on total alcohol intake (consumed grams of alcohol/week) and pattern of drinking, as well as medical, childhood and adolescent conditions, and tobacco use. Adjustments were made for socio-economic position as a child, psychiatric symptoms and emotional stability, and the father's alcohol habits.

"We found that lower results on IQ tests in Swedish adolescent men are associated with a higher consumption of alcohol, measured in both terms of total intake and binge drinking," said Sjölund. "It may be that a higher IQ results in healthier lifestyle choices. Suggested explanations for the association between IQ and different health outcomes, could be childhood conditions, which could influence both IQ and health, or that a socio-economic position as an adult mediates the association."

"By taking into account as little as four measured characteristics of the men, including their backgrounds," added Falkstedt, "the authors seem to be able to explain a large part of the association between IQ and heavy drinking. I think this may be a main message of this large cohort study: poor performance on IQ tests tend to go along with other disadvantages, for instance, poorer social background and emotional problems, which may explain the association with risky alcohol consumption. In reality, other differences of importance are likely to exist among the men, which could further explain the IQ-alcohol association."

Both Sjölund and Falkstedt noted that results may vary among cultures and countries.

"I think that large parts of the association between IQ and alcohol consumption may be indirect and mediated by experiences in everyday life and differences in social situations," said Falkstedt. "It is not necessarily about making intelligent or unintelligent choices. For instance, in countries with weak social-safety nets and high alcohol consumption among low-wage workers and the unemployed, I assume the association could be stronger than in economically more-equal countries, perhaps also among the young."

"I hope that our findings add to the general understanding of drinking behaviours and what factors that may influence them," said Sjölund. "However, we must be very careful in making any attempt to generalize our results to women, since their level of consumption and patterns of drinking likely differ in comparison with men."

"I think a higher intelligence may give some advantage in relation to lifestyle choices," noted Falkstedt. "However, I think it is very important to remember that intelligence differences already existing in childhood and adolescence may put people at an advantage or disadvantage and may generate subsequent differences in experiences, and accumulation of such experiences over many years. Therefore, another important explanation of 'bad choices' among lower-IQ individuals may be feelings of inadequacy and frustration, I think. A number of studies have shown that a lower IQ in childhood or adolescence is associated with an increased risk of suicide over many years in adulthood."

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Caribbean coral findings may influence Barrier Reef studies

Corals may be better equipped to tolerate climate change than previously believed, according to research led by Griffith University's Dr Emma Kennedy.

Working with scientists from the University of Exeter in the UK, Dr Kennedy says the findings -- published in the journal Coral Reefs -- relate to an extensive study of Caribbean corals, but could influence future analysis of Australia's Great Barrier Reef.

Using a high-resolution molecular screening technique called Real Time-PCR, the researchers confirmed that the partnership between Symbiodinium D -- a symbiotic algae associated with resistance to coral bleaching -- and Caribbean corals is more common than had been supposed.

"Corals rely on a relationship with algae in order to get energy via photosynthesis," says Dr Kennedy, a Postdoctoral Research Fellow in the School of Environment's Australian Rivers Institute.

"However, under stressful conditions such as increased temperatures, this relationship can be disrupted, resulting in a loss of the algae in an event known as bleaching. In an extreme event, this can lead to coral death.

"Our study focused on populations of the Mountain Star coral, Orbicella annularis, a widespread and prominent reef species in the Caribbean.

"Understanding its ability to weather the pressures of a changing climate, in particular rising sea temperatures, is a key question for conservationists."

Symbiodinium D was found to be present in low abundances at almost every location the researchers tested, from Tobago to the Bahamas. As well as being geographically widespread, it was also more common in individuals, found on average in more than 30 per cent of the corals in each location.

Dr Kennedy says previous studies have shown that if Orbicella annularis contains just a small amount of Symbiodinium D it can sometimes respond better to stress events -- such as heatwaves -- and is more likely to avoid coral bleaching.

A 2007 research paper (Mieog et al. 2007, Coral Reefs) reported the presence of Symbiodinium D in 71 per cent of coral colonies tested on the Great Barrier Reef.

Having completed her PhD at the University of Exeter, Dr Kennedy's latest research involves assessing the responses of coralline algae to ocean acidification and warming. It aims to determine whether coralline algae can be used to track the impacts of climate change in the Great Barrier Reef.

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Bacterial Memories: Host influences bacterial metabolism

Bacteria are masters in adapting to their environment. This adaptability contributes to the bacteria's survival inside their host. Researchers at the Vetmeduni Vienna now demonstrated that the bacterial pathogen Listeria monocytogenes adapts its metabolism specifically to the host genotype. The bacterial metabolic fingerprint correlated with the susceptibility of the infected mouse strain. The researchers published their results in the journal Plos One.

Bacteria are known to specifically adapt to host environments. Understanding these adaptation mechanisms is crucial for the development of effective therapeutics.

Mouse lineage influences bacterial metabolism

Monika Ehling-Schulz's group from the Institute of Microbiology, together with Mathias Müller's group at the Institute of Animal Breeding and Genetics studied the influence of host organisms on bacterial metabolism. The researchers infected three different lineages of mice with the bacteria Listeria monocytogenes. The mouse strains showed significant differences in their response to the infection and in the severity of the clinical symptoms.

The researchers isolated the bacteria days after infection and analysed them for changes in their metabolism. They used a specific infrared spectroscopy method (FTIR) to monitor metabolic changes. The chemometric analysis of the bacterial metabolic fingerprints revealed host genotype specific imprints and adaptations of the bacterial pathogen.

"Our findings may have implications on how to treat infectious diseases in general. Every patient is different and so are their bacteria," first author Tom Grunert states.

Memory effect in bacteria

After isolation from the mice, all bacteria were cultured under laboratory conditions. After prolonged cultivation under laboratory conditions all three bacterial batches switched back to the same metabolic fingerprint. "Based on our results it can be assumed that bacteria have some sort of memory. It takes some time under host-free laboratory conditions for this 'memory effect' to vanish," explains the head of the Institute, Monika Ehling-Schulz.

Vibrating molecules decipher bacterial metabolism

The researchers employed a technique known as Fourier-transform infrared (FTIR) spectroscopy to monitor the metabolism in the bacteria. An infrared beam directed through the bacteria causes molecules such as proteins, polysaccharides and fatty acids to vibrate. The molecules variably allow more or less light to pass. The different molecular composition in the bacteria yields different spectral data providing information about the molecules inside.

"This method is used especially in microbiological diagnostics to identify bacteria. But we refined the method to decipher and monitor differences in the metabolic fingerprint of the same bacteria," says Grunert.

In the future, the researchers want to extend the concept to other species of bacteria and further study the impact of host organisms on pathogens. In a next step, the team plans to find out what exactly it is, that leads to metabolic changes in bacteria.

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Insect and mammal ovulation more alike than not?

The average American woman lives more than 80 years and ovulates for 35 of them, producing an egg approximately once a month. The typical fruit fly lives about 4 weeks as an adult and ovulates every 30 minutes. Now researchers at the University of Connecticut report in PLOS Genetics that during a key process, the same gene may govern both. If correct, the results could bring insight to cancer metastasis, human fertility and ovarian disease.

We have a general idea of the timing of and the hormones involved in ovulation in humans. What we don't understand are the precise mechanics regulating how the egg escapes from the follicle of cells encasing it in the ovary. Does the egg shove its way out? Does the follicle bloom like a flower? What genes govern the process, and what do they do?

Researchers have tried to study the genetic mechanics of ovulation in designer 'knock-out' mice, which have one gene taken out of commission (or 'knocked-out'). But mice often have multiple, related genes in their genome and these genes can compensate for each other, so the process often still works even if a single gene is removed.

Fruit flies have a less-redundant genome and a faster life cycle than mice, making them much easier to work with. But researchers had assumed that insects are so far apart from us evolutionarily that their ovulatory process would be totally different.

Not so, according to Jianjun Sun and colleagues in UConn's department of physiology and neurobiology and their collaborator Allan Spradling at the Carnegie Institution for Science. In the February 19 issue of PLOS Genetics they report two critical parts of ovulation that seem to be the same in both flies and mice. The first is cellular, and has to do with the fate of the follicle cells after the egg escapes. Sun's team found that just as in mammals, in flies the follicle cells blocking the path of the egg out of the ovary degrade and slough off at ovulation. And just as in mammals, the follicle cells left behind inside the ovary after the egg escapes turn yellowish and produce steroid hormones essential for fertility.

The second has to do with Matrix metalloproteinase (Mmp), an enzyme that researchers suspect mammals need to break down the cellular matrix of the follicle in order for the egg to escape. Mice have 24 genes that code for Mmp: fruit flies have just two, mmp1 and mmp2. Sun and his colleagues found that knocking out just mmp2 all by itself reduced the mmps enzyme levels in a fly's ovaries, and dramatically reduced the number of eggs laid. This work provide the first genetic evidence that Mmp is required for ovulation and its role is likely conserved between flies and mice.

These similarities suggest that the basics of ovulation are very similar in animals generally.

"The evolutionary distance between flies and mice is so huge, compared to the distance between mouse and human. Everything that is conserved between fly and mouse is likely be conserved in humans," Sun says. The findings provide a foundation for other researchers to find out exactly which genes are required for ovulation in flies, and so for mice, and so for humans.

The research could prove immediately applicable to fertility disorders in humans such as polycystic ovary syndrome (PCOS), in which women don't ovulate. Sun's group is utilizing its fly system to look at PCOS now. But their findings could also prove useful to understanding the way cancer spreads through the body. When cancers metastasize, individual cells escape from the tumor mass and spread into the bloodstream. How exactly cancer cells escape from their original cell matrix may have something to do with the Mmp enzyme, Sun says, and that means this research could eventually inform treatments that block a cancer's spread.

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Probiotic toxin fights coldwater disease in rainbow trout

The trout food is coated with the Coldwater Disease-fighting probiotic developed by Cain and Call.

The rainbow trout is a work of art and diner's delight. But when the freshwater fish falls prey to Coldwater Disease, its colorful body erodes into ragged wounds and ulcers. The bacterial infection can kill up to 30 percent of hatchery stock and causes millions of dollars in economic loss.

After 15 years of research, scientists at University of Idaho and Washington State University have found a simple and effective method to combat Coldwater Disease using some of the trout's own intestinal bacteria as health-giving probiotics.

They also showed that the probiotics work by secreting a toxic protein, which does not harm the fish but does kill the Coldwater Disease organism, Flavobacterium psychrophilum.

Douglas Call, professor in the WSU School for Global Animal Health reported the findings in the publication, Applied and Environmental Microbiology in January. The study was funded in part by the Western Regional Aquaculture Center and the Idaho State Board of Education.

"Coldwater Disease is the number one bacterial illness affecting U.S. trout aquaculture and to a lesser extent Coho salmon," said Call. "Once an outbreak starts, the only way we've had to treat it has been with antibiotics."

"The problem with antibiotics is that they can lead to bacterial resistance and also contaminate the water and soil," he said. "Only two antibiotics are approved for use and one, florfenicol, is particularly nasty and persists in the environment for a very long time."

Call said the probiotics could be a cheap and effective alternative to antibiotics -- and welcome news to the global salmonid aquaculture industry whose annual production tops out at more than $13.7 billion.

How does it work?

Kenneth Cain, professor and associate director of the Aquaculture Research Institute at University of Idaho, recently discovered the probiotic, a now patented strain of Enterobacter species called C6-6.

Probiotics, broadly speaking, are live bacteria and yeast that are beneficial to your health. Lactobacilli bacteria, for example, are commonly used in yogurt and livestock feed to help promote disease resistance and overall health. Cain said probiotics are commercialized for use in European fisheries, but have only recently been considered for U.S. aquaculture.

To find the C6-6 probiotic, Cain and his colleagues painstakingly searched through 318 strains of bacteria from the GI tracts of trout until they identified those that could kill the Coldwater microorganism. He chose to examine the trout's native gut bacteria because such strains were able to survive in the fish's digestive system.

Subsequent field trials showed significantly reduced mortality rates from the disease in fish that were fed strain C6-6, but as is common with many probiotics, the scientists really didn't know how it worked.

Call, an expert in bacterial molecular biology, collaborated with WSU graduate student Carla Schubiger to pinpoint the mechanism that makes the trout probiotic effective.

"We found C6-6 produces a toxic protein called an entericidin which inhibits the Coldwater bacteria," he said. "It could also present new opportunities for treatments against closely related pathogens."

Plus it's economical.

"The bacteria that produce the entericidin are fast growing, cheap to produce and easy to put on food for the fish -- all the attributes of an ideal preventative treatment," said Call.

A combined approach

Although Coldwater Disease occurs in the wild, Cain said it is most prevalent in commercial trout and salmon hatcheries where crowding and stress lead to frequent outbreaks -- a point of concern for Pacific Northwest growers.

Idaho trout farms produce about 75 percent of U.S. and nearly 50 percent of the worldwide trout harvest. Neighboring Washington State leads the nation in production of trout eggs, a commodity sold to hatcheries around the globe.

"It costs the Idaho trout farm industry and Washington aquaculture facilities over $10 million each year to combat Coldwater Disease," said Cain. "Controlling it will take more than one tool."

Cain recently patented a vaccine for the disease that is in the process of being licensed. He and Call agree that vaccinating fish to prevent Coldwater Disease followed by the feeding of probiotics to limit its spread would be beneficial.

Thanks to the discovery of the C6-6 entericidin, Call said he is hopeful for regulatory approval and commercial licensing of the probiotic as well.

"If C6-6 is as effective as our research is showing, it will reduce disease losses for fish producers, improve animal welfare and reduce the demand for antibiotics in aquaculture."

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Gene may help reduce GM contamination

Genetically modified crops have long drawn fire from opponents worried about potential contamination of conventional crops and other plants. Now a plant gene discovered by University of Guelph scientists might help farmers reduce the risk of GM contamination and quell arguments against the use of transgenic food crops, says Sherif Sherif, lead author of a new research paper describing the findings.

This is believed to be the first-ever study to identify a gene involved in altering fruit trees that normally cross-pollinate -- needing one plant to fertilize another -- into self-pollinators, said Sherif.

The paper was published recently in the journal BMC Biology.

Sherif said researchers might one day insert this gene into GM crops to prevent their pollen from reaching other plants.

Plant agriculture professor Jay Subramanian, Sherif's PhD supervisor and a co-author on the paper, said: "There are a lot of transgenic crops worldwide. There is concern about pollen from them being able to fertilize something in the wild population, thus creating 'super weeds.'"

The researchers found a gene making a protein that naturally allows a small handful of plants to self-pollinate and make fruit before the flower opens. Peaches, for example, have closed flowers, unlike their showy-flowered plum and cherry cousins that need pollen from another tree to fertilize and set fruit.

Subramanian studies tree fruits at the Vineland Research and Innovation Centre in Vineland, Ont. Sherif worked with him on studies of plant responses to stresses such as drought or disease.

Other co-authors on the paper are Guelph professors Jaideep Mathur, Department of Molecular and Cellular Biology and Gopi Paliyath, Department of Plant Agiruclture, along with Islam El-Sharkawy, a former research associate with Subramanian; and colleagues at the National University of Singapore.

Besides aiding crop farmers and food producers, their discovery might be a boon to perfume-makers, said Subramanian.

Used in fragrant perennials such as jasmine, the gene might keep flowers closed and allow growers to collect more of the aromatic compounds prized by perfume-makers. "That's when volatile compounds are peaking," said Subramanian. "When the flower opens, you lose almost 80 per cent of those volatiles."

Most plants develop open flowers to attract pollinators, but it takes energy to make flowers as well as nectar and pollen. Subramanian said plants with closed flowers -- called cleistogamous, or Greek for "closed marriage" -- might have developed in environments lacking pollinators or under adverse conditions.

"This is the first time we know of that someone has shown that, using molecular tools, you can induce cleistogamy in plants," he said.

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Invasive weed Kochia's resistance to well-known herbicide stems from increase in gene copies

Kochia, invasive weed populations that are taking over crops and non-crop areas in western Kansas and the Great Plains.

A recent study by a Kansas State University weed scientist finds why the invasive weed kochia is like a cockroach of the plant world.

Mithila Jugulam, assistant professor of agronomy, led a study that looked at how kochia -- invasive weed populations that are taking over crops and non-crop areas in western Kansas and the Great Plains -- evolved resistance to the most used herbicide glyphosate, more commonly known as Roundup Weed Killer. Researchers found that kochia has evolved to have multiple copies of a gene code that targets glyphosate. These copies enable the plants to survive the field rate of glyphosate applications.

"It's a very novel resistance mechanism and is becoming prevalent in a number of glyphosate-resistant weeds, including Palmer amaranth, common waterhemp and kochia," Jugulam said.

Jugulam conducted the study in collaboration with Kansas State University's Bikram Gill, university distinguished professor of plant pathology.

The journal Plant Physiology recently published their study, "Tandem Amplification of a Chromosomal Segment Harboring 5-Enolpyruvylshikimate-3-Phosphate Synthase Locus Confers Glyphosate Resistance in Kochia scoparia." It is the first study to find a molecular cytogenetic basis of EPSPS gene amplification in kochia.

Glyphosate works by stopping an enzyme called EPSPS that is crucial for production of aromatic amino acids in the shikimic acid pathway. If EPSPS is disrupted, the plant eventually dies.

Using an innovative technique called fluorescence in situ hybridization, or Fiber FISH, on kochia's DNA fragment, the team found that glyphosate-resistant kochia had duplicated several EPSPS copies that stacked alongside each other on a single chromosome.

Researchers also found that the more copies of EPSPS kochia had, the higher tolerance it had against glyphosate. For example, kochia plants with nine to 12 EPSPS copies could survive twice the recommended amount of glyphosate, while a plant with 16 copies could withstand six times the amount.

While the increase in EPSPS gene copies has created a nonsustainable way of controlling kochia with glyphosate-only programs, Jugulam said this resistance was evolved as the result of continuous use of glyphosate and the lack of herbicide diversity in controlling this weed.

"Herbicides are not known to cause mutations in plants," Jugulam said. "The resistant individuals present in the population initially are at low levels and slowly dominate over the susceptible plants if selection with the same herbicide continues."

Currently, Jugulam and colleagues are looking at kochia from across the U.S. and Canada to find whether plants from other areas in the world have evolved the same way. This may shed light on the future control methods.

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Proteins pull together as cells divide

A cleavage furrow begins to separate a dividing cell into daughter cells.

Like a surgeon separating conjoined twins, cells have to be careful to get everything just right when they divide in two. Otherwise, the resulting daughter cells could be hobbled, particularly if they end up with too many or two few chromosomes. Successful cell division hangs on the formation of a dip called a cleavage furrow, a process that has remained mysterious. Now, researchers at Johns Hopkins have found that no single molecular architect directs the cleavage furrow's formation; rather, it is a robust structure made of a suite of team players.

The finding is detailed in the March 2 issue of the journal Current Biology.

"We assumed the cleavage furrow was like a finely tuned Swiss watch, in that breaking a key component would bring it to a stop -- we just didn't know what that component was," says Douglas Robinson, Ph.D., a professor of cell biology in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine, borrowing an analogy from the late Ray Rappaport, the founding father of modern cell division research. "But it turned out to be more like an old Maine fishing boat: almost indestructible."

Cell division is how new cells form, both during development and throughout an organism's life. To learn more about this process, Robinson and graduate student Vasudha Srivastava took the one-celled amoeba Dictyostelium as their model. One by one, they disabled genes for proteins known to be involved in the cleavage furrow to see whether doing so disrupted its assembly. But no matter which protein was taken out, other proteins still self-assembled to form the cleavage furrow. "It's not a house of cards -- pulling out one protein doesn't bring it down," Srivastava says. Instead, she and Robinson found a robust process tuned not only by chemical signaling, but also by mechanical processes.

That makes sense, Robinson says, given the importance of the cleavage furrow to life itself. "Cells need to get division right in order to avoid ending up with the wrong number of chromosomes, which can be fatal," he says.

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New brain mapping reveals unknown cell types

There are estimated to be 100 million cells in a mouse brain, and 65 billion in a human brain. Nerve cells are approximately 20 micrometres in diameter, glial cells about 10 micrometres. A micrometre is equivalent to a thousandth of a millimetre.

Using a process known as single cell sequencing, scientists at Karolinska Institutet have produced a detailed map of cortical cell types and the genes active within them. The study, which is published in the journal Science, marks the first time this method of analysis has been used on such a large scale on such complex tissue. The team studied over three thousand cells, one at a time, and even managed to identify a number of hitherto unknown types.

"If you compare the brain to a fruit salad, you could say that previous methods were like running the fruit through a blender and seeing what colour juice you got from different parts of the brain," says Sten Linnarsson, senior researcher at the Department of Medical Biochemistry and Biophysics. "But in recent years we've developed much more sensitive methods of analysis that allow us to see which genes are active in individual cells. This is like taking pieces of the fruit salad, examining them one by one and then sorting them into piles to see how many different kinds of fruit it contains, what they're made up of and how they interrelate."

The knowledge that all living organisms are built up of cells is almost 200 years old. Since the discovery was made by a group of 19th century German scientists, we have also learnt that the nature of a particular body tissue is determined by its constituent cells, which are, in turn, determined by which genes are active in their DNA. However, little is still known about how this happens in detail, especially as regards the brain, the body's most complex organ.

In the present study, the scientists used large-scale single-cell analysis to answer some of these questions. By studying over three thousand cells from the cerebral cortex in mice, one at a time and in detail, and comparing which of the 20,000 genes were active in each one, they were able to sort the cells into virtual piles. They identified 47 different kinds of cell, including a large proportion of specialised neurons, some blood vessel cells and glial cells, which take care of waste products, protect against infection and supply nerve cells with nutrients.

With the help of this detailed map, the scientists were able to identify hitherto unknown cell types, including a nerve cell in the most superficial cortical layer, and six different types of oligodendrocyte, which are cells that form the electrically insulating myelin sheath around the nerve cells. The new knowledge the project has generated can shed more light on diseases that affect the myelin, such as multiple sclerosis (MS).

"We could also confirm previous findings, such as that the pyramidal cells of the cerebral cortex are functionally organised in layers," says Jens Hjerling-Leffler, who co-led the study with Dr Linnarsson. "But above all, we have created a much more detailed map of the cells of the brain that describes each cell type in detail and shows which genes are active in it. This gives science a new tool for studying these cell types in disease models and helps us to understand better how brain cell respond to disease and injury."

There are estimated to be 100 million cells in a mouse brain, and 65 billion in a human brain. Nerve cells are approximately 20 micrometres in diameter, glial cells about 10 micrometres. A micrometre is equivalent to a thousandth of a millimetre.

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New nanogel for drug delivery: Self-healing gel can be injected into the body and act as a long-term drug depot

Syringe (stock image). A newly developed gel consists of a mesh network made of two components: nanoparticles made of polymers entwined within strands of another polymer, such as cellulose.

Scientists are interested in using gels to deliver drugs because they can be molded into specific shapes and designed to release their payload over a specified time period. However, current versions aren't always practical because must be implanted surgically.

To help overcome that obstacle, MIT chemical engineers have designed a new type of self-healing hydrogel that could be injected through a syringe. Such gels, which can carry one or two drugs at a time, could be useful for treating cancer, macular degeneration, or heart disease, among other diseases, the researchers say.

The new gel consists of a mesh network made of two components: nanoparticles made of polymers entwined within strands of another polymer, such as cellulose.

"Now you have a gel that can change shape when you apply stress to it, and then, importantly, it can re-heal when you relax those forces. That allows you to squeeze it through a syringe or a needle and get it into the body without surgery," says Mark Tibbitt, a postdoc at MIT's Koch Institute for Integrative Cancer Research and one of the lead authors of a paper describing the gel in Nature Communications on Feb. 19.

Koch Institute postdoc Eric Appel is also a lead author of the paper, and the paper's senior author is Robert Langer, the David H. Koch Institute Professor at MIT. Other authors are postdoc Matthew Webber, undergraduate Bradley Mattix, and postdoc Omid Veiseh.

Heal thyself

Scientists have previously constructed hydrogels for biomedical uses by forming irreversible chemical linkages between polymers. These gels, used to make soft contact lenses, among other applications, are tough and sturdy, but once they are formed their shape cannot easily be altered.

The MIT team set out to create a gel that could survive strong mechanical forces, known as shear forces, and then reform itself. Other researchers have created such gels by engineering proteins that self-assemble into hydrogels, but this approach requires complex biochemical processes. The MIT team wanted to design something simpler.

"We're working with really simple materials," Tibbitt says. "They don't require any advanced chemical functionalization."

The MIT approach relies on a combination of two readily available components. One is a type of nanoparticle formed of PEG-PLA copolymers, first developed in Langer's lab decades ago and now commonly used to package and deliver drugs. To form a hydrogel, the researchers mixed these particles with a polymer -- in this case, cellulose.

Each polymer chain forms weak bonds with many nanoparticles, producing a loosely woven lattice of polymers and nanoparticles. Because each attachment point is fairly weak, the bonds break apart under mechanical stress, such as when injected through a syringe. When the shear forces are over, the polymers and nanoparticles form new attachments with different partners, healing the gel.

Using two components to form the gel also gives the researchers the opportunity to deliver two different drugs at the same time. PEG-PLA nanoparticles have an inner core that is ideally suited to carry hydrophobic small-molecule drugs, which include many chemotherapy drugs. Meanwhile, the polymers, which exist in a watery solution, can carry hydrophilic molecules such as proteins, including antibodies and growth factors.

Long-term drug delivery

In this study, the researchers showed that the gels survived injection under the skin of mice and successfully released two drugs, one hydrophobic and one hydrophilic, over several days.

This type of gel offers an important advantage over injecting a liquid solution of drug-delivery nanoparticles: While a solution will immediately disperse throughout the body, the gel stays in place after injection, allowing the drug to be targeted to a specific tissue. Furthermore, the properties of each gel component can be tuned so the drugs they carry are released at different rates, allowing them to be tailored for different uses.

The researchers are now looking into using the gel to deliver anti-angiogenesis drugs to treat macular degeneration. Currently, patients receive these drugs, which cut off the growth of blood vessels that interfere with sight, as an injection into the eye once a month. The MIT team envisions that the new gel could be programmed to deliver these drugs over several months, reducing the frequency of injections.

Another potential application for the gels is delivering drugs, such as growth factors, that could help repair damaged heart tissue after a heart attack. The researchers are also pursuing the possibility of using this gel to deliver cancer drugs to kill tumor cells that get left behind after surgery. In that case, the gel would be loaded with a chemical that lures cancer cells toward the gel, as well as a chemotherapy drug that would kill them. This could help eliminate the residual cancer cells that often form new tumors following surgery.

"Removing the tumor leaves behind a cavity that you could fill with our material, which would provide some therapeutic benefit over the long term in recruiting and killing those cells," Appel says. "We can tailor the materials to provide us with the drug-release profile that makes it the most effective at actually recruiting the cells."

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Animals tend to evolve toward larger size over time

Does evolution follow certain rules? If, in the words of the famed evolutionary biologist Stephen Jay Gould, one could "rewind the tape of life," would certain biological trends reemerge? Asked another way: can evolution be predicted?

New research suggests that, for at least one important biological trait-body size-the answer is yes.

In one of the most comprehensive studies of body size evolution ever conducted, Stanford scientists have found fresh support for Cope's rule, a theory in biology that states that animal lineages tend to evolve toward larger sizes over time.

"We've known for some time now that the largest organisms alive today are larger than the largest organisms that were alive when life originated or even when animals first evolved," said Jonathan Payne, a paleobiologist at Stanford's School of Earth, Energy & Environmental Sciences.

What was unclear, however, was whether the average size of animals has been changing over time and, if so, whether that reflects a trend, or directionality, in body size evolution. "It's not something that you can know by just studying living organisms or extrapolating from what you see over short time scales. If you do that, you will absolutely be wrong about the rate, and possibly also the direction," Payne said.

The study, published in the Feb. 20 issue of the journal Science, reveals that over the past 542 million years, the mean sized of marine animals has increased 150-fold. "That's the size difference between a sea urchin that is about 2 inches long versus one that is nearly a foot long," Heim said. "This may not seem like a lot, but it represents a big jump."

The research also found that the increase in body size that has occurred since animals first appeared in the fossil record around 550 million years ago is not due to all animal lineages steadily growing bigger, but rather to the diversification of groups of organisms that were already larger than other groups early in the history of animal evolution.

"That's also something we didn't know before," Payne said. "For reasons that we don't completely understand, the classes with large body size appear to be the ones that over time have become differentially more diverse."

A universal trend?

Named after paleontologist Edward Cope, Cope's rule was formulated in the late 19th century after paleontologists noticed that the body sizes of terrestrial mammals such as horses generally increased over time.

Scientists have attempted to test Cope's rule in other animal groups, but the conclusions have been mixed. Corals and dinosaurs seem to follow Cope's rule, for example, but birds and insects do not. As a result, some scientists have wondered whether the pattern observed in land mammals is a real evolutionary phenomenon or merely a statistical one resulting from random, non-selective evolution, also known as neutral drift. "It's possible that as evolution proceeds, there really is no preference for being larger or smaller," said Noel Heim, a postdoctoral researcher in Payne's lab. "What appears to be an increase in average body size may be due to neutral drift."

To test whether Cope's rule applies to marine animals as a whole, Payne and a team that included undergraduates and high school interns compiled a dataset including more than 17,000 groups, or genera, of marine animals spanning five major phyla-Arthropods, Brachiopods, Chordates, Echinoderms, and Mollusks-and the past 542 million years. "Our study is the most comprehensive test of Cope's rule ever conducted," Heim said. "Nearly 75 percent of all of marine genera in the fossil record and nearly 60 percent of all the animal genera that ever lived are included in our dataset."

To compile such a vast dataset, the team relied heavily on the Treatise on Invertebrate Paleontology, a 50-volume book set that includes detailed information about every invertebrate animal genus with a fossil record known to science. Using photographs and detailed illustrations of fossils in the Treatise, the team was able to calculate and analyze body size and volume for 17,208 marine genera.

A pattern soon became apparent: not all classes-groups of related species and genera-of animals trended toward larger size, but those that were bigger tended to become more diverse over time. The team suspects this is due to advantages associated with a larger size, such as the ability to move faster, burrow more deeply and efficiently in sediment, or capture larger prey.

"It's really a story of the survival and diversification of big things relative to small things," Heim said.

Virtual evolution

To investigate what might drive these trends toward larger body sizes, the team entered their measurement data into a computer model designed to simulate body size evolution. Beginning with the smaller species from each phylum, the model simulated how their body sizes might change as they evolved into new species. "As time marches forward, each species is assigned some probability of producing a new species, of remaining the same, or of going extinct, at which point it drops out of the race," Heim said.

When a new virtual species was created, the model assigned the new creature a body size that could be bigger or smaller than its ancestor. The scientists ran multiple simulations, each with different assumptions. One scenario, for instance, assumed a neutral drift model of evolution, in which body size fluctuates randomly without affecting the survival of the species. Another assumed natural selection, or "active evolution," of body size, in which having a larger body size confers certain survival advantages and is thus more likely to propagate through the generations.

The team found that the neutral drift simulation could not explain the body size trends observed in the fossil record. "The degree of increase in both mean and maximum body size just aren't well explained by neutral drift," Heim said. "It appears that you actually need some active evolutionary process that promotes larger sizes."

The team believes that the vast database they compiled will be useful for studying other questions related to body size, such as whether or not organisms near the equator are, on average, bigger or smaller than those living at higher latitudes.

The findings could also prompt other scientists to investigate whether there is a trend in the evolution of other traits. "The discovery that body size often does evolve in a directional way makes it at least worth asking whether we're going to find directionality in other traits if we measure them carefully and systematically," Payne said.

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