0000-0002-9890-5451The potential of using machine learning techniques in medicine is immense. As electronic health records have become widely available, there is hope that machine learning will improve diagnosis and care. However, integrating these new methodologies
In late December 2013, PLOS ONE published an article from UK-based Psychologists Rob Jenkins and Christie Kerr titled “Identifiable Images of Bystanders Extracted from Corneal Reflections”. Using high-resolution photography, Jenkins, from the University of York, and Kerr, from the University … Continue reading
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Launched in 2010, the Neuromapping and Therapeutics Collection is a unique collaboration between PLOS ONE and the Society for Brain Mapping and Therapeutics. The Neuromapping and Therapeutics Collection provides a forum for interdisciplinary research aimed at translation of knowledge across a number of fields such as neurosurgery, neurology, psychiatry, radiology, neuroscience, neuroengineering, and healthcare and policy issues that affect the treatment delivery and usage of related devices, drugs, and technologies. The Collection is open to submissions on these topics from any researcher—so far, 24 research papers have been published as part of this Collection.
We spoke to Dr. Allyson Rosen, one of the members of the Society for Brain Mapping and Therapeutics who helps coordinate the Neuromapping and Therapeutics Collection, to discuss the latest news and research in this area, and the new submissions to the collection they’re hoping to see in the next few months:
What’s exciting in Neuromapping and Therapeutics at the moment?
It is exciting to see how creative scientists and clinicians are at solving important clinical problems by combining diverse techniques in innovative ways. We see our collection as a home for cross-disciplinary work that might not “fit” in traditional journals. For example, we have published MR methods to enable effective brain infusions and work that exploits computer-aided design for cranial reconstructions. There are invasive and non-inva
What are the implications of President Obama’s commitment to Human Brain Mapping research?sive techniques for stimulating selective brain regions and creating focal lesions, such as transcranial magnetic stimulation, transcranial Doppler technology, and X-ray microplanar beam technology. There are also innovative analysis techniques that exploit powerful computational methods that were previously unavailable.
Given the high-profile nature of the Brain Mapping Initiative and the state of the US economy, we have advocated that there be some clinical implications to the announcement. We believe that this approach will ensure continued public support at a time of great need and uncertainty.
Are there any specific research areas where you’d like to see more submissions to the Collection?
We are proud of the work we’ve received and deeply impressed with the broad array of papers submitted so far. This is a testament to the creativity of our contributors, and we welcome their diversity. We particularly welcome work presented at the international meeting of the Society for Brain Mapping and Therapeutics that occurs in the spring of each year.
Why do you think it’s important to publish this kind of research in an open access journal such as PLOS ONE?
Our society is committed to being inclusive and welcoming any profession that seeks to improve the health and wellbeing of patients with brain disorders. An open access journal enables easier promotion of work we feel is important and encourages sharing among diverse disciplines. Often, truly cutting-edge work is so far ahead of its time that there is not yet an appreciation for its importance. Often, clinical problems are seen as practical but not necessarily novel. We appreciate the mission of PLOS ONE as upholding strong scientific integrity and not as triaging work based on arbitrary decisions regarding importance.
To read more about this Collection, including new research papers like, “Verifying three-dimensional skull model reconstruction using cranial index of symmetry” and “Unique anti-glioblastoma activities of Hypericin are at the crossroad of biochemical and epigenetic events and culminate in Tumor Cell Differentiation,” click here.
Come visit us at SFN 2013.
Both the Society for Brain Mapping and Therapeutics and PLOS ONE will be attending SFN 2013 – please drop by booth #136 to say hello and learn more about the Collection. For instructions on how to submit to the Collection, please visit the Collection page and download the submission document.
If you have any questions about this Collection, or any other PLOS Collections, please email email@example.com
Image credit for Collection cover: Alka Joshi
In the business of survival, the bright colors of blooming flowers mark a serious transaction. Their nectar, color and fragrances are all designed to attract pollinators to come hither and transfer pollen to help plants reproduce but occasionally, these plans go awry. Some bees choose to avoid the pollen and tunnel into flowers to steal nectar instead. A study published in PLOS ONE last week explains how plants deter these robbers by providing them a map to reach nectar more quickly. Author Anne Leonard explains their results:
How did you become interested in studying floral guide patterns?
I think many people are intrigued by the fact that bees see the patterns on flowers differently than we do. I was studying color learning in bumble bees, and as I looked through the literature I realized there were still many unanswered questions about how these patterns affect bees’ behavior. Living in Tucson, I started to photograph the dazzling variety of nectar guides on Sonoran desert wildflowers, slowing down many a hike in the process. Between all the reading and photography, I clearly had nectar guides on the brain.
Why do flowers have nectar guide patterns?
The patterns of nectar guides appear to be very attractive to many bee species. Bright colors, high color contrasts and star-like outlines could simply help a plant increase visits from pollinators. It’s even been suggested that these visual features might have evolved to mimic rewards, for example bright yellows and oranges might resemble protein-rich pollen to the insects. Secondly, plants that produce distinctive and memorable patterns might also benefit because they provide an identifying feature for pollinators to learn, remember, and return to.
Third, a nectar guide may reduce the overall time the bee spends on the flower. If bees are sensitive to the time costs associated with visiting different flowers, then they should prefer to visit flowers they can handle quickly. Finally, our research suggests a novel benefit: the pattern can reduce a bee’s tendency to rob nectar. In this case, the pattern benefits the plant by incentivizing the bee to access nectar “legitimately,” in a way that is most likely to transfer pollen.
If you take a moment and imagine a bee visiting a trumpet-shaped flower like a morning glory, what you’re picturing is most likely what we call a “legitimate” visit. The bee lands on a petal, and walks forward to probe down to the nectar located in the tube-like part of the flower. In the process, she is likely to pick up pollen or transfer pollen from her body to the flower. This exchange of nectar for pollen transfer forms the basis of the relationship between plant and bee. We refer to this type of nectar for pollen transfer via the floral opening as a “legitimate” visit, from the plant’s perspective.
In a second type of visit, the bee lands on the flower but instead of going the legitimate route, it bites a hole in the side of the flower to access nectar, without necessarily depositing pollen or picking up new pollen. Because the plant has lost nectar to the bee without gaining pollen transfer, this type of visit is termed ‘nectar robbing’.
Although observations of bees nectar robbing date back to at least the 18th century writings of Sprengel, we are still studying why bees do it. Some species, like carpenter bees, have a reputation as frequent robbers. Others like honey bees and the bumble bee species I study, Bombus impatiens, are better known as opportunistic nectar robbers. They’ll rob some plant species but not others; propensity to rob seems to also vary somewhat across individuals. Some studies show that bees may be more likely to rob if a previous visitor has already created the access hole. Likewise, our research suggests that if the flower doesn’t have a nectar guide pattern to direct the bee to the floral opening, they are more likely to stray and encounter an access hole left by a previous robber.
In your paper, you found that when a flower had a guide pattern, bees were less likely to rob nectar. How did you test the bees’ behavior?
We use an array of specially designed artificial flowers that my co-author Josh Brent spent many hours trouble-shooting. These flowers had nectar available in two different ways. The bee could either land on the top of the flower and access nectar “legitimately” from a small central well, or she could land on the underside of the flower, and “rob” nectar from a small well located on the side of the floral tube.
We kept bee colonies in the lab so they were naïve with respect to experience with real flowers. We let bees into the arena one at a time, and recorded their visits to the flowers on the array. Half the bees were given blue flowers with yellow star-shaped guides, and the other half saw only plain blue flowers with no patterns. We noted whether the bee robbed or visited each flower legitimately, and we were also able to measure how quickly she located the nectar after landing in each case.
We found that bees robbed less frequently when the flowers had nectar guides and also landed more quickly on flowers with guides than those without them. This suggests the bees indeed found the nectar guide more attractive to land upon than the plain flower top, and that the guide helped them find nectar faster.
Does this discovery have applications for bee-keepers or horticulturists?
We’d need a few more of the pieces of the puzzle before claiming that our research on floral patterns might yield better honey or healthier honeybees, but our research suggests that the stripes and dots that provide color patterns pleasing to the human eye can also affect the way the bee interacts with the flower.
Typically, varieties of nursery plants are bred for human aesthetics. Given a choice, planting a variety with a dramatic nectar guide pattern might allow an observant gardener the satisfaction of seeing more pollen transferred by bees. On the other hand, those gardeners eager to see nectar robbing in action might select a relatively plain variety. The committed backyard scientist might be inspired to plant varieties with different types of patterns, sit back, and watch what happens. Of course, flowers of different plants can also differ in many other aspects that might affect a bee’s propensity to rob nectar (such as floral scent or nectar chemistry) and keep in mind that some may have UV patterns that the human eye can’t see.
Citation and images: Leonard AS, Brent J, Papaj DR, Dornhaus A (2013) Floral Nectar Guide Patterns Discourage Nectar Robbing by Bumble Bees. PLoS ONE 8(2): e55914. doi:10.1371/journal.pone.0055914
Small pieces of RNA in our cells can act like molecular switches that turn genes off by binding to them. These pieces, called small interfering RNAs (siRNAs) are also used by researchers to design experiments to understand what certain genes do.
Scientists can design siRNA molecules aimed at turning off specific genes they are trying to study. Though such siRNA ‘switches’ can be very useful, they are often non-specific, turning off hundreds of genes that they should not have an effect on. As a result, it is difficult for a biologist to conclude whether an experimentally observed effect is due to turning off the gene they meant to turn off or the hundreds that they didn’t (called “off-target effects”). Eugen Buehler of the National Center for Advancing Translational Sciences (NCATS), a new center at the NIH, describes an alternate approach to dealing with these off-target effects of siRNAs in his recent PLOS ONE paper. Read on to find out more about this research:
How did you become interested in improving siRNA experiments?
I’ve been working on siRNAs for about the last five years. When I would talk to my wife (a cell biologist) about my research, I would go on and on about all the problems created by these non-specific effects. Since she uses siRNAs in her research, she would ask, “Well, what should I do to avoid it?”
I didn’t have an answer. All the methods I had involved a statistical analysis of a large number of results from high-throughput screens, which look at several thousand genes at once. They couldn’t be applied to experiments that only involved one or a few genes, which is what many researchers do. It frustrated me not being able to help her, and so this question of what to do about off-target effects in small-scale experiments kept nagging me, until I found an answer.
And what was that answer?
As is often the case, the answer involved looking at the problem a different way. For years, people have been trying to solve the problem by getting rid of the non-specific effects. There are many ways to do this, but they still have a high incidence of these effects.
So, rather than trying to eliminate the off-target activity, we took the opposite approach. We changed three points (bases 9-11) where an siRNA makes contact with its target, so it couldn’t have the effect it was designed for. In this way, we created the C911 version, an anti-siRNA of sorts, which had all the off-target effects but none of the on-target effects.
So if an siRNA has an effect in a cell that is different from what the C911 version of the same siRNA has, we can conclude that the effect is because it silenced the intended target.
Which figure in the manuscript do you think best summarizes your results?
Definitely Figure 3B. Here, we compare siRNAs that appear to have specific effects but don’t (false positives), with ones that do have a specific action on a target gene. We took ten of each kind and created C911 versions for all twenty.
When we compared the two we found that for the false positives, the siRNA and the anti-siRNA had the same effects (left hand panel). But for the siRNAs which really did have an effect on their target, there was a big difference between the siRNA and its C911 version. As it happened, the C911 controls worked perfectly for all twenty siRNAs we had selected for the experiment.
Where do you hope to go from here?
For a tool as well established as siRNA, it will take a while to change the way we design our experiments. The first step is for there to be a reasonable alternative, and that is what this paper is meant to supply. The next is to make that alternative easy to choose. Part of that will involve getting companies that manufacture siRNAs to eventually make negative controls like this, so that negative controls like C911 can be easily and affordably obtained for any siRNA.
My hope is that someday when a researcher orders an siRNA, they won’t even have to ask; they’ll get a tube with their siRNA and a tube with the appropriate negative control by default.
Citation: Buehler E, Chen Y-C, Martin S (2012) C911: A Bench-Level Control for Sequence Specific siRNA Off-Target Effects. PLoS ONE 7(12): e51942. doi:10.1371/journal.pone.0051942
Image: Target by Ivan McClellan on flickr