Tag: Biomedical

For research published on March 27 in Science, a team at Rockefeller University tracked the appearance and disappearance of these protein coats within the blood of mice infected by Trypanosoma brucei. Their results reveal an unexpected diversity in disguises present at any one time and challenge the conventional understanding of the dynamics that allow the parasite to persist. Spread by the Tsetse fly in rural Africa, T. brucei travels through the blood and across the blood-brain barrier to cause potentially fatal disease that disrupts circadian rhythms, hence the name sleeping sickness. T. brucei, like the malaria parasite and some other pathogens, relies on antigenic variation to stay one step ahead of their hosts’ immune systems. Here’s how it works. Many animals, including humans, have immune systems capable of learning to recognize pathogens based on those pathogens’ antigens, usually proteins on their surface. After encountering an antigen, the immune system generates its own proteins called antibodies to target that antigen. By continually changing antigens, a pathogen evades those antibodies.

T. brucei’s protein disguise comes from a family of variant surface glycoproteins (VSGs). At any time, a single VSG covers the parasite and, during an infection, the parasites in the bloodstream periodically switch to a new VSG. Together with Nina Papavasiliou and André and Bella Meyer Professor Emeritus George Cross, Monica Mugnier, a graduate student in Papavasiliou’s lab, set out to take a close look at these switches by tracking the VSG genes expressed over time during an infection. “Little is known about the dynamics of VSG switching by the sleeping sickness parasite. What is known is that the coat is highly antigenic and stimulates a very strong immune response that wipes out most of the parasite population. The prevailing paradigm regarding the ability of the parasite to evade the immune response comes from studies completed decades ago, which suggested that a parasite changes its coat and stimulates an immune response on a weekly basis. Monica’s work totally upends this picture, and therefore the assumptions about how this parasite interacts with the immune response” says study author Associate Professor Nina Papavasiliou, head of the Laboratory of Lymphocyte Biology.

A novel technique Mugnier developed to track the rise and fall of individual VSGs over time made this new insight possible. , “Previously, it was assumed that, as the immune system begins to recognize a parasites’ VSG and clear it, only one or a few VSGs would emerge to make up the next wave of parasites. However, our results contradict this paradigm,” Mugnier says. “We find as many as 80 distinct trypanosome coats at any given time.” “This has substantial implications for the interaction of this parasite with its host” says Cross. For example, it is now clear that the diversity of the VSGs required to maintain an extended infection exceeds the number of functional genes responsible for encoding them. This raised a question, since T. brucei infections can last for years. How does the parasite generate enough unique VSGs to continue fending off the immune system for that long, considering its repertoire of pre-existing genes?

Previous research suggested the answer: by mixing and matching. T. brucei has nearly 2,000 functioning and nonfunctioning VSG genes. By recombining these, the parasite can create many new disguises. This mechanism is likely a crucial source of VSG diversity for the parasite, according to the researchers, who identified a number of so-called mosaic VSGs, and, for the first time, documented the timing of their appearance during the course of the infection. “Antigenic variation is both key to T. brucei‘s success and its Achilles’ heel. This strategy has made it impossible to develop a vaccine against sleep sickness, but without antigenic variation this parasite would not stand a chance against a healthy immune system,” Mugnier says. “The methods we developed lay the foundation for a better understanding of the diseases caused by African trypanosomes, and by other pathogens whose long-term infections are facilitated by antigenic variation, which could improve our strategies for fighting these infections.”

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http://www.sciencedaily.com/releases/2015/03/150326162608.htm  Original web page at Science Daily

The study, which projected the effects of climate-related changes on habitats of 162 species of birds and 39 species of mammals within 403,000 acres of the arctic, is among the first to explore what a warming climate might mean for a wide array of bird and mammal species across a vast geographic area. The findings are published in the journal Climatic Change. “Climate is changing in the arctic far faster — by some estimates, twice as fast — than in lower-latitude temperate regions,” said Bruce Marcot, a research wildlife biologist with the Pacific Northwest Research Station who led the analysis. “This makes the arctic, in a way, an ‘early warning system’ for the rest of the continent, making projections of changes in the region a very important scientific tool.”

In their study, Marcot and his colleagues used three approaches to project changes in vegetation and land cover through the 21st century along with wildlife-habitat relationship models that, together, summarize what scientists know about how ecosystems and wildlife habitats can be affected by rising temperature and associated drivers such as the expansion of tall shrubs and trees, increase in fire, and melting of permafrost. The researchers then projected the availability of wildlife habitat by relating recent and projected vegetation changes to the habitats of the region’s birds and mammals. The study revealed that up to 52 percent of the 201 bird and mammal species currently occurring in the area would experience habitat expansion under the models, 45 percent would see habitat contractions, and 3 percent would experience no habitat change. Species whose habitats are projected to expand include those occupying forest and tall-shrub habitats, such as grouse and black bear, while species whose habitats are projected to decline include those occupying meadow and low-shrub habitats, like ptarmigan and caribou as well as most of the small mammals that form the prey base for larger carnivores and raptors.

Marcot and his colleagues also found that a greater proportion of mammal species would experience habitat declines than would bird species. In addition, half of the 50 bird and mammal species used for subsistence hunting, including greater white-fronted goose, tundra swan, caribou, mink, and muskrat would experience habitat decline. “I view our work as producing testable working hypotheses that can be validated and refined over time through further studies and monitoring,” Marcot said. “It is a first approximation and not a definitive prediction of changes in wildlife population sizes to come, so continued studies will help refine our predictions and likely provide some surprises as the region continues to change.”

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http://www.sciencedaily.com/releases/2015/04/150403233713.htm  Original web page at Science Daily

Researchers at the Durrell Institute of Conservation and Ecology (DICE) at the University of Kent say that with over 4 million km² of tropical forests harvested for timber worldwide, improving the way logging impacts on wildlife is essential for global biodiversity conservation. Members of DICE conducted the most comprehensive study of Reduced-Impact Logging (RIL) to date, surveying wildlife communities over a five-year period before and after timber harvesting. The research team, comprising Dr Jake Bicknell, Dr Matthew Struebig and Dr Zoe Davies, discovered that RIL had very little effect on the birds, bats and large mammals in the rainforests of Central Guyana.

In fact, they found that the natural rates of change in the wildlife communities were greater than those resulting from this type of modern, best-practice logging technique. Now the researchers hope the new evidence, showing the benefits of adopting RIL over conventional logging, will encourage governments and timber companies to make the switch in their timber industry practices. Dr Bicknell said the research demonstrated that RIL is a ‘cost-effective option’ that will ensure the long-term sustainability of biodiversity-rich tropical forests around the world. It is better for wildlife because it ‘minimises collateral damage to unlogged trees in the forest, and reduces gaps in the forest canopy which are associated with conventional logging’.

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http://www.sciencedaily.com/releases/2015/02/150227112647.htm  Original web page at Science Daily

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? 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.” 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. 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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http://www.sciencedaily.com/releases/2015/02/150219144635.htm  Original web page at Science Daily

For more than a century, scientists have understood the basics of inheritance: if good genes help parents survive and reproduce, the parents pass those genes along to their offspring. And yet, recent research has shown that reality is much more complex: genes can be switched off, or silenced, in response to the environment or other factors, and sometimes these changes can be passed from one generation to the next. The phenomenon has been called epigenetic inheritance, but it is not well understood. Now, UMD geneticist Antony Jose and two of his graduate students are the first to figure out a specific mechanism by which a parent can pass silenced genes to its offspring. Importantly, the team found that this silencing could persist for multiple generations–more than 25, in the case of this study. The research, which was published in the Feb. 2, 2015 online early edition of the Proceedings of the National Academy of Sciences, could transform our understanding of animal evolution. Further, it might one day help in the design of treatments for a broad range of genetic diseases. “For a long time, biologists have wanted to know how information from the environment sometimes gets transmitted to the next generation,” said Jose, an assistant professor in the UMD Department of Cell Biology and Molecular Genetics. “This is the first mechanistic demonstration of how this could happen. It’s a level of organization that we didn’t know existed in animals before.” Jose and graduate students Sindhuja Devanapally and Snusha Ravikumar worked with the roundworm Caenorhabditis elegans, a species commonly used in lab experiments. They made the worms’ nerve cells produce molecules of double-stranded RNA (dsRNA) that match a specific gene. (RNA is a close relative of DNA, and has many different varieties, including dsRNA.) Molecules of dsRNA are known to travel between body cells (any cell in the body except germ cells, which make egg or sperm cells) and can silence genes when their sequence matches up with the corresponding section of a cell’s DNA. The team’s biggest finding was that dsRNA can travel from body cells into germ cells and silence genes within the germ cells. Even more surprising, the silencing can stick around for more than 25 generations. If this same mechanism exists in other animals–possibly including humans–it could mean that there is a completely different way for a species to evolve in response to its environment. “This mechanism gives an animal a tool to evolve much faster,” Jose said. “We still need to figure out whether this tool is actually used in this way, but it is at least possible. If animals use this RNA transport to adapt, it would mean a new understanding of how evolution happens.” The long-term stability of the silencing effect could prove critical in developing treatments for genetic diseases. The key is a process known as RNA interference, more commonly referred to as RNAi. This process is how dsRNA silences genes in a cell. The same process has been studied as a potential genetic therapy for more than a decade, because you can target any disease gene with matching dsRNA. But a main obstacle has been achieving stable silencing, so that the patient does not need to take repeated high doses of dsRNA. “RNAi is very promising as a therapy, but the efficacy of the treatment declines over time with each new cell division,” Jose said. “This particular dsRNA, from C. elegans nerve cells, might have some chemical modifications that allow stable silencing to persist for many generations. Further study of this molecule could help solve the efficacy problem in RNAi therapy.” Jose acknowledges the large gap between roundworms and humans. Unlike simpler animals, mammals have known mechanisms that reprogram silenced genes every generation. On the surface, it would seem as though this would prevent epigenetic inheritance from happening. And yet, previous evidence suggests that the environment may be able to cause some sort of transgenerational effect in mammals as well. Jose believes that his team’s work provides a promising lead in the search for how this happens. “This is a fertile research field that will keep us busy for 10 years or more into the future,” Jose said. “The goal is to achieve a very clear understanding–in simple terms–of all the tools an animal can use to evolve.”

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http://www.sciencedaily.com/releases/2015/02/150202212449.htm  Original web page at Science Daily

Neurons in the brain are wired like a social network, report researchers from Biozentrum, University of Basel. Each nerve cell has links with many others, but the strongest bonds form between the few cells most similar to each other. The results are published in the journal Nature. Nerve cells form a bewildering meshwork of connections called synapses — up to several thousand per cell. Yet not all synaptic connections are equal. The overwhelming majority of connections are weak, and cells make only very few strong links. “We wanted to see if there are rules that explain how neurons connect in complex networks comprising millions of neurons,” says Professor Thomas Mrsic-Flogel, the leader of the research team from the Biozentrum (University of Basel) and UCL (University College London). “It turns out that one of the rules is quite simple. Like-minded neurons are strongly coupled, while neurons that behave very differently from each other connect weakly or not at all.” The researchers focused on the visual area of the cerebral cortex, which receives information from the eye and gives rise to visual perception. Neurons in this part of the brain respond to particular visual patterns, but it is difficult to untangle which cells are synaptically connected because there are many thousands of them densely packed (close to 100,000 per cubic millimeter). Using a combination of high resolution imaging and sensitive electrical measurements, the researchers found that connections between nearby neurons are organized like a social network. Sites like Facebook keep us in contact with large numbers of acquaintances, but most people have a much smaller circle of close friends. These are usually the friends with which we have most in common, and their opinions can be more important to us than the views of the rest. “Weak contacts in the brain have little impact, despite being in the majority,” says Mrsic-Flogel. “The few strong connections from neurons with similar functions exert the strongest influence on the activity of their partners. This could help them work together to amplify specific information from the outside world.” But why do neurons share such large numbers of weak connections? “We think this might have to do with learning,” says Dr Lee Cossell, one of the lead authors of the study. “If neurons need to change their behavior, weak connections are already in place to be strengthened, perhaps ensuring rapid plasticity in the brain.” As a result, the brain could quickly adapt to changes in the environment. This research is part of worldwide effort to shed light on how the brain generates perceptions, thoughts and actions by mapping the brain’s wiring diagram. “It reveals how networks of neurons interact together to process information. Understanding how neurons connect will pave the way for building detailed computer simulations of the brain,” says Mrsic-Flogel. Research that explores how neurons connect will also be important for understanding neurological diseases. “If we know what the pattern of connections in the brain should look like, then we can start to figure out what happens when things go wrong, for example, in schizophrenia or autism,” adds Mrsic-Flogel.

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http://www.sciencedaily.com/releases/2015/02/150204134127.htm  Original web page at Science Daily

Researchers observed that when cell bodies were activated but the dendrites were not activated during an animal’s experience, a lasting memory of that experience was not formed by the neurons. This suggests that the cell body seems to represent ongoing experience, while dendrites, the treelike branches of a neuron, help to store that information. Why do we remember some things and not others? In a unique imaging study, two NorthwesternUniversity researchers have discovered how neurons in the brain might allow some experiences to be remembered while others are forgotten. It turns out, if you want to remember something about your environment, you better involve your dendrites.

Using a high-resolution, one-of-a-kind microscope, Daniel A. Dombeck and Mark E. J. Sheffield peered into the brain of a living animal and saw exactly what was happening in individual neurons called place cells as the animal navigated a virtual reality maze. The scientists found that, contrary to current thought, the activity of a neuron’s cell body and its dendrites can be different. They observed that when cell bodies were activated but the dendrites were not activated during an animal’s experience, a lasting memory of that experience was not formed by the neurons. This suggests that the cell body seems to represent ongoing experience, while dendrites, the treelike branches of a neuron, help to store that experience as a memory. “There are a lot of theories on memory but very little data as to how individual neurons actually store information in a behaving animal,” said Dombeck, assistant professor of neurobiology in the Weinberg College of Arts and Sciences and the study’s senior author. “Now we have uncovered signals in dendrites that we think are very important for learning and memory. Our findings could explain why some experiences are remembered and others are forgotten.” In the brain’s hippocampus, there are hundreds of thousands of place cells — neurons essential to the brain’s GPS system. Dombeck and Sheffield are the first to image the activity of individual dendrites in place cells. Their findings contribute to our understanding of how the brain represents the world around it and also point to dendrites as a new potential target for therapeutics to combat memory deficits and debilitating diseases, such as Alzheimer’s disease (AD). Disruption to the brain’s GPS system is one of the first symptoms of AD, with many patients unable to find their way home. Understanding how place cells and their dendrites store these types of memories could help us find new ways to treat the disease. The Northwestern study was published Oct. 26 by the journal Nature. Neuroscientist John O’Keefe discovered place cells in 1971 (and received this year’s Nobel Prize in physiology and medicine), but it is only in the last few years that scientists, such as Dombeck and Sheffield, have been able to image these neurons that represent a map of where we are in our environment. In their study, Dombeck and Sheffield found dendrite signals that could explain how an animal can experience something without storing the experience as a memory.

They saw that dendrites are not always activated when the cell body is activated in a neuron. Signals produced in the dendrites (used to store information) and signals within the neuron cell body (used to compute and transmit information) can be either highly synchronized or desynchronized depending on how well the neurons remember different features of the maze. Scientists have long believed that the neuronal tasks of computing and storing information are connected — when neurons compute information, they are also storing it, and vice versa. The Northwestern study provides evidence against this classic view of neuronal function. “We experience events all the time, which must be represented in the brain by the activity of neurons, but not all these events can be recalled later,” said Mark E. J. Sheffield, a postdoctoral fellow in Dombeck’s lab and first author of the study. “A daily commute to work, for example, requires the activity of millions of neurons, but you would be hard pressed to remember what was happening halfway through your commute last Tuesday,” Sheffield said. “How is it then that the neurons could be activated during the commute without storing that information in the brain? Now we may have an explanation for how this occurs.” Dombeck and Sheffield built their own laser scanning microscope that can image neurons on multiple planes. They then studied individual animals navigating (on a trackball) a virtual reality maze constructed using the video game Quake II. Each lit-up structure seen in the images they took indicate a neuron firing action potentials. The activity of these neurons represents an animal’s experience of where it is in the environment, the researchers said. Whether the neurons store this experience or not appears to depend on the activity of the neurons’ dendrites.

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http://www.sciencedaily.com/releases/2014/10/141026195336.htm  Original web page at Science Daily

Parasitic bacteria were the first cousins of the mitochondria that power cells in animals and plants — and first acted as energy parasites in those cells before becoming beneficial, according to a new University of Virginia study that used next-generation DNA sequencing technologies to decode the genomes of 18 bacteria that are close relatives of mitochondria. The study appears this week in the online journal PLoS ONE, published by the Public Library of Science. It provides an alternative theory to two current theories of how simple bacterial cells were swallowed up by host cells and ultimately became mitochondria, the “powerhouse” organelles within virtually all eukaryotic cells — animal and plant cells that contain a nucleus and other features. Mitochondria power the cells by providing them with adenosine triphosphate, or ATP, considered by biologists to be the energy currency of life. The origin of mitochondria began about 2 billion years ago and is one of the seminal events in the evolutionary history of life. However, little is known about the circumstances surrounding its origin, and that question is considered an enigma in modern biology. “We believe this study has the potential to change the way we think about the event that led to mitochondria,” said U.Va. biologist Martin Wu, the study’s lead author. “We are saying that the current theories — all claiming that the relationship between the bacteria and the host cell at the very beginning of the symbiosis was mutually beneficial — are likely wrong. “Instead, we believe the relationship likely was antagonistic — that the bacteria were parasitic and only later became beneficial to the host cell by switching the direction of the ATP transport.” The finding, Wu said, is a new insight into an event in the early history of life on Earth that ultimately led to the diverse eukaryotic life we see today. Without mitochondria to provide energy to the rest of a cell, there could not have evolved such amazing biodiversity, he said. “We reconstructed the gene content of mitochondrial ancestors, by sequencing DNAs of its close relatives, and we predict it to be a parasite that actually stole energy in the form of ATP from its host — completely opposite to the current role of mitochondria,” Wu said. In his study, Wu also identified many human genes that are derived from mitochondria — identification of which has the potential to help understand the genetic basis of human mitochondrial dysfunction that may contribute to several diseases, including Alzheimer’s disease, Parkinson’s disease and diabetes, as well as aging-related diseases. In addition to the basic essential role of mitochondria in the functioning of cells, the DNA of mitochondria is used by scientists for DNA forensics, genealogy and tracing human evolutionary history

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http://www.sciencedaily.com/releases/2014/10/141016165955.htm  Original web page at Science Daily

The pond-dwelling, single-celled organism Oxytricha trifallax has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it’s time to mate, the researchers report in the journal Cell. The organism internally stores its genome as thousands of scrambled, encrypted gene pieces. Upon mating with another of its kind, the organism rummages through these jumbled genes and DNA segments to piece together more than 225,000 tiny strands of DNA. This all happens in about 60 hours. The organism’s ability to take apart and quickly reassemble its own genes is unusually elaborate for any form of life, explained senior author Laura Landweber, a Princeton professor of ecology and evolutionary biology. That such intricacy exists in a seemingly simple organism accentuates the “true diversity of life on our planet,” she said. “It’s one of nature’s early attempts to become more complex despite staying small in the sense of being unicellular,” Landweber said. “There are other examples of genomic jigsaw puzzles, but this one is a leader in terms of complexity. People might think that pond-dwelling organisms would be simple, but this shows how complex life can be, that it can reassemble all the building blocks of chromosomes.” From a practical standpoint, Oxytricha is a model organism that could provide a template for understanding how chromosomes in more complex animals such as humans break apart and reassemble, as can happen during the onset of cancer, Landweber said. While chromosome dynamics in cancer cells can be unpredictable and chaotic, Oxytricha presents an orderly step-by-step model of chromosome reconstruction, she said. “It’s basically bad when human chromosomes break apart and reassemble in a different order,” Landweber said. “The process in Oxytricha recruits some of the same biological mechanisms that normally protect chromosomes from falling apart and uses them to do something creative and constructive instead.” Gertraud Burger, a professor of biochemistry at the University of Montreal, said that the “rampant and diligently orchestrated genome rearrangements that take place in this organism” demonstrate a unique layer of complexity for scientists to consider when it comes to studying an organism’s genetics. “This work illustrates in an impressive way that the genetic information of an organism can undergo substantial change before it is actually used for building the components of a living cell,” said Burger, who is familiar with the work but had no role in it.

“Therefore, inferring an organism’s make-up from the genome sequence alone can be a daunting task and maybe even impossible in certain instances,” Burger said. “A few cases of minor rearrangements have been described in earlier work, but these are dilettantes compared to this system.” Burger added that the work is “extremely comprehensive as to the experimental techniques employed and analyses performed.” The project is one of the first complex genomes to be sequenced using Pacific Biosciences (PacBio) technology that reads long, single molecules. Oxytricha already stands apart from other microorganisms, Landweber said. It is a large cell, about 10 times the size of a typical human cell. The organism also contains two nuclei whereas most single-celled organisms contain just one. A cell’s nucleus regulates internal activity and, typically, contains the cell’s DNA as well as the genes that are passed along during reproduction. An individual Oxytricha cell, however, keeps its active DNA in one working nucleus and uses the second to store an archive of the genetic material it will pass along to the next generation, Landweber said. The genome of this second nucleus — known as the germ-line nucleus — undergoes the dismantling and reconstruction to produce a new working nucleus in the offspring. Oxytricha uses sex solely to exchange DNA rather than to reproduce, Landweber said — like plant cuttings, new Oxytricha populations spawn from a single organism. During sex, two organisms fuse together to share half of their genetic information. The object is for each cell to replace aging genes with new genes and DNA parts from its partner. Together, both cells construct new working nuclei with a fresh set of chromosomes. This rejuvenates them and diversifies their genetic material, which is good for the organism, Landweber said. “It’s kind of like science fiction — they stop aging by trading in their old parts,” she said. It’s during this process that the scrambled genes in the germ-line nucleus are sorted through to locate the roughly 225,000 small DNA segments that each mate uses to reconstruct its rejuvenated chromosomes, the researchers found. Previous work in Landweber’s lab — a 2012 publication in Cell and a 2008 paper in the journal Nature — showed that millions of noncoding RNA molecules from the previous generation direct this undertaking by marking and sorting the DNA pieces in the correct order. Also impressive is the massive scale of Oxytricha‘s genome, Landweber said. A 2013 paper from her lab in PLoS Biology reported that the organism contains approximately 16,000 chromosomes in the active nucleus; humans have only 46. Most of Oxytricha‘s chromosomes contain just a single gene, but even those genes can get hefty. A single Oxytricha gene can be built up from anywhere between one to 245 separate pieces of DNA, Landweber said. The exceptional genetics of Oxytricha protect its DNA, so that mainly healthy material is passed along during reproduction, Landweber said. It’s no wonder then that the organism can be found worldwide munching on algae. “Their successful distribution across the globe has something to do with their ability to protect their DNA through a novel method of encryption, then rapidly reassemble and transmit robust genes across generations,” Landweber said.

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http://www.sciencedaily.com/releases/2014/09/140908152926.htm  Original web page at Science Daily

Bats appear to use a network of hair-thin muscles in their wing skin to control the stiffness and shape of their wings as they fly, according to a new study. The finding provides new insight about the aerodynamic fine-tuning of membrane wings, both natural and human-made. A new study of bats reveals a capability within their wondrous wings that may help them fine-tune their flight. Bats employ a network of nearly hair-thin muscles embedded in the membrane of their inherently floppy wing skin to adjust the wings’ stiffness and curvature while they fly, BrownUniversity researchers report. Birds and insects have stiff wings, but the new evidence suggests bats have evolved this muscular means of preserving or adjusting wing shape. “Aerodynamic performance depends upon wing shape,” said Brown biology graduate student Jorn Cheney, lead author of the newly published paper in Bioinspiration and Biomimetics. “The shape of a membrane wing might initially begin flat but as soon as it starts producing lift it’s not going to remain flat because it has to deform in response to that aerodynamic load. “The shape it adopts could be a terrible one — it could make the animal crash — or it could be beneficial,” Cheney said. “But they are not locked into that shape. Because bats have these muscles in their wings, and also bones that can control the general shape as well, they can adopt any number of profiles.” Cheney wasn’t sure what to make of the tiny muscles, called plagiopatagiales, heading into the experiments reported in the paper. They have been known for more than a century but their function has never been demonstrated. When Cheney considered the muscle function, he estimated that each individual muscle would be too weak to reshape the wing. That led him to form two competing hypotheses: either that the muscles would activate together to enhance force or that these oddly shaped, weak muscles might exist solely as sensors of stretch.

Only experiments could settle the question, so Cheney attached electrode sensors to a few muscles on the wings of a few Jamaican fruit bats and filmed them as they flew in the lab’s wind tunnel. Three key findings emerged from the data. They all point to the plagiopatagiales modulating skin stiffness. One result was that the muscle activation and relaxation follows a distinct pattern during flight: They tense on the downstroke and relax on the upstroke. “This is the first study showing that bats turn these muscles on and off during a typical wingbeat cycle,” said co-author Sharon Swartz, professor of biology at Brown. .Another finding was that the muscles don’t act individually. Instead they exert their force in synchrony, providing enough collective strength to stiffen the wing. Finally, Cheney found, the muscles appeared to activate with different timing at different flight speeds. As the bats flew faster, they tensed the muscles sooner in the upstroke-downstroke cycle. In other words, the data suggested that the muscles do not behave passively but actively and collectively in keeping with conditions of flight. None of the data, however, preclude the muscles from serving a sensory function as well. Cheney’s findings fit into a larger program of research at Brown between the labs of biologist Swartz and co-author Kenneth Breuer, professor of engineering, in which, as Breuer puts it, they are “using biology to inspire engineering and using engineering to inspire biology.” In parallel with studies of real bats, the team has also built a robotic bat wing that incorporates their biological observations. Then they use the wing to generate data from experiments that they could never do with living creatures, such as precisely varying kinematic parameters like wingbeat frequency and amplitude, or the degree of wing folding during flapping.

http://www.sciencedaily.com/  Science Daily

June 24, 2014

http://www.sciencedaily.com/releases/2014/05/140523145348.htm  Original web page at Science Daily

Cells usually self-destruct when irreparable glitches occur in their DNA. Programmed cell death, or apoptosis, helps insure that cells with damaged DNA do not grow and replicate to produce more mutated cells. Apoptosis thereby helps protect and insure the survival of the organism. At the GSA Drosophila Research Conference, TinTin Su, Ph.D., will report that a dying Drosophila melanogaster larvae cell alerts neighboring cells that they are in danger of suffering a similar fate. Dr. Su and her collaborators at University of Colorado, Boulder used ionizing radiation (IR) to induce DNA damage and apoptosis in cells of the wing imaginal disc, the immature form of the fly’s wings. The neighboring cells responded by activating bantam, a microRNA. As a result, the neighboring cells became more difficult to kill by IR. The scientists determined that the key to this process was the receptor tyrosine kinase Tie. The dying cell’s signal turned on Tie, thereby activating the short microRNA molecule bantam. Previously the only known role for Tie in fruit flies was in long-range signaling in border cell migration. Although Tie is not required for normal larval development, it becomes necessary for survival after radiation exposure, Dr. Su noted. The dying cell’s signaling its neighbors to protect themselves from apoptosis challenges the long held view that cells in the vicinity of dying, irradiated cells become more prone to death. The results of the experiments conducted by Dr. Su and her collaborators also complement previous studies that showed that a larval disc cell’s death leads to proliferation of cells in the disc. If this protective mechanism also operates in mammals, it may affect the results of the sequential use of cytotoxic agents and radiation in cancer therapy, she pointed out.

http://www.sciencedaily.com/ Science Daily

April 15, 2014

http://www.sciencedaily.com/releases/2014/03/140327111231.htm  Original web page at  Science Daily

Four pesticides commonly used on crops to kill insects and fungi also kill honeybee larvae within their hives, according to Penn State and University of Florida researchers. The team also found that N-methyl-2-pyrrolidone (NMP) — an inert, or inactive, chemical commonly used as a pesticide additive — is highly toxic to honeybee larvae. “We found that four of the pesticides most commonly found in beehives kill bee larvae,” said Jim Frazier, professor of entomology, Penn State. “We also found that the negative effects of these pesticides are sometimes greater when the pesticides occur in combinations within the hive. Since pesticide safety is judged almost entirely on adult honeybee sensitivity to individual pesticides and also does not consider mixtures of pesticides, the risk assessment process that the Environmental Protection Agency uses should be changed.” According to Frazier, the team’s previous research demonstrated that forager bees bring back to the hive an average of six different pesticides on the pollen they collect. Nurse bees use this pollen to make beebread, which they then feed to honeybee larvae.

To examine the effects of four common pesticides — fluvalinate, coumaphos, chlorothalonil and chlorpyrifos — on bee larvae, the researchers reared honeybee larvae in their laboratory. They then applied the pesticides alone and in all combinations to the beebread to determine whether these insecticides and fungicides act alone or in concert to create a toxic environment for honeybee growth and development. The researchers also investigated the effects of NMP on honeybee larvae by adding seven concentrations of the chemical to a pollen-derived, royal jelly diet. NMP is used to dissolve pesticides into formulations that then allow the active ingredients to spread and penetrate the plant or animal surfaces onto which they are applied. The team fed their treated diet, containing various types and concentrations of chemicals, to the laboratory-raised bee larvae. The team’s results are reported in the current issue of PLoS ONE. “We found that mixtures of pesticides can have greater consequences for larval toxicity than one would expect from individual pesticides,” Frazier said. Among the four pesticides, honeybee larvae were most sensitive to chlorothalonil. They also were negatively affected by a mixture of chlorothalonil with fluvalinate. In addition, the larvae were sensitive to the combination of chlorothalonil with the miticide coumaphos. In contrast, the addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture.

According to Chris Mullin, professor of entomology, Penn State, these pesticides may directly poison honeybee larvae or they may indirectly kill them by disrupting the beneficial fungi that are essential for nurse bees to process pollen into beebread. “Chronic exposure to pesticides during the early life stage of honeybees may contribute to their inadequate nutrition or direct poisoning with a resulting impact on the survival and development of the entire bee brood,” he said. The researchers note that fluvalinate and coumaphos are commonly used by beekeepers on crops to control Varroa mites, and are found to persist within beehives for about five years. Chlorothalonil is a broad-spectrum agricultural fungicide that is often applied to crops in bloom when honeybees are present for pollination because it is currently deemed safe to bees. Chlorpyrifos is a widely used organophosphate in crop management. “Our findings suggest that the common pesticides chlorothalonil, fluvalinate, coumaphos and chloropyrifos, individually or in mixtures, have statistically significant impacts on honeybee larval survivorship,” Mullin said. “This is the first study to report serious toxic effects on developing honeybee larvae of dietary pesticides at concentrations that currently occur in hives.”

The team also found that increasing amounts of NMP corresponded to increased larval mortality, even at the lowest concentration tested. “There is a growing body of research that has reported a wide range of adverse effects of inactive ingredients to human health, including enhancing pesticide toxicities across the nervous, cardiovascular, respiratory and hormone systems,” Mullin said. “The bulk of synthetic organic chemicals used and released into U.S. environments are formulation ingredients like NMP, which are generally recognized as safe. They have no mandated limits on their use and their residues remain unmonitored. “Multi-billion pounds of these inactive ingredients overwhelm the total chemical burden from the active pesticide, drug and personal-care ingredients with which they are formulated. Among these co-formulants are surfactants and solvents of known high toxicity to fish, amphibians, honey bees and other non-target organisms. While we have found that NMP contributes to honeybee larvae mortality, the overall role of these inactive ingredients in pollinator decline remains to be determined.”

http://www.sciencedaily.com/ Science Daily
February 18, 2014

http://www.sciencedaily.com/releases/2014/01/140127122825.htm Original web page at Science Daily

In a finding that directly contradicts the standard biological model of animal cell communication, UCSF scientists have discovered that typical cells in animals have the ability to transmit and receive biological signals by making physical contact with each other, even at long distance. The mechanism is similar to the way neurons communicate with other cells, and contrasts the standard understanding that non-neuronal cells “basically spit out signaling proteins into extracellular fluid and hope they find the right target,” said senior investigator Thomas B. Kornberg, PhD, a professor of biochemistry with the UCSF Cardiovascular Research Institute. The paper was published on January 2, 2014 in Science. Working with living tissue from Drosophila — fruit flies — Kornberg and his team demonstrated that cells send out long, thin tubes of cytoplasm called cytonemes, which Kornberg said “can extend across the length of 50 or 100 cells” before touching the cells they are targeting. The point of contact between a cytoneme and its target cell acts as a communications bridge between the two cells.

“It’s long been known that neurons communicate in a similar way — by transferring signals at points of contact called synapses, and transmitting the response over long distances in long tubes called axons,” said Kornberg. “However, it’s always been thought that this mode of signaling was unique to neurons. We have now shown that many types of animal cells have the same ability to reach out and synapse with one another in order to communicate, using signaling proteins as units of information instead of the neurotransmitters and electrical impulses that neurons use.” In fact, said Kornberg, “I would argue that the only strong experimental data that exists today for a mechanism by which these signaling proteins move from one cell to another is at these points of contact and via cytonemes.” However, he noted, “There are 100 years worth of work and thousands of scientific papers in which it has been simply assumed that these proteins move from one cell to another by moving through extracellular fluid. So this is a fundamentally different way of considering how signaling goes on in tissues.” Working with cells in the Drosophila wing that produce and send the signaling protein Decapentaplegic (Dpp), Kornberg and his team showed that Dpp transfers between cells at the sites where cytonemes form a connection, and that cytonemes are the conduits that move Dpp from cell to cell.

The scientists discovered that the sites of contact have characteristics of synapses formed by neurons. They demonstrated that in flies that had been genetically engineered to lack synapse-making proteins, cells are unable to form synapses or signal successfully. “In the mutants, the signals that are normally taken up by target cells are not taken up, and signaling is prevented,” said Kornberg. “This demonstrates that physical contact is required for signal transfer, signal uptake and signaling.” Kornberg said that a major reason that animal cell cytonemes had not been observed or studied previously is because these structures are too fragile to survive traditional laboratory methods of preparing cells for imaging. “During the last decade or so, though, there have been fantastic technical advances, including new techniques in genetic engineering, new microscopes that improve the resolution and sensitivity for imaging living cells and the development of fluorescent marker proteins that we can attach to proteins of interest.” Using these new technologies, Kornberg and his team have captured vivid images, and even movies, of fluorescent signaling proteins moving through fluorescently marked cytonemes. “We are not saying that cells always use cytonemes for signaling,” Kornberg cautioned. “Hormones, for example, are another method of long distance cell signaling.

A cell that takes up insulin does not care where that insulin came from — a pancreas or an intravenous injection. But there are signals of a specialized type, such as those that pass between stem cells and the cells around them, or signals that determine tissue growth, patterning and function, where the identity of the communicating cells must be precisely defined. It’s important that these signals are received in the context of the cells that are making them.” Kornberg noted that other research teams have made observations that suggest that cytoneme-based signaling may also occur “between stem cells and the cells that instruct them on what they are going to do and where they are going to go.” Cancer cells may also use this method to communicate with their neighbors, he said. The discovery of animal cell cytonemes and the critical role they play in long distance signaling “opens up a wonderful biology of which we have very little understanding at this point,” said Kornberg. “For example, how do these cytonemes find their targets? How do they know when they have found them? These are some of the questions that we are pursuing.”

Science Daily
January 21, 2014

Original web page at Science Daily

Caterpillars of two species of butterflies in Colorado and California have evolved to feed rapidly at higher temperatures and at a broader range of temperatures over the past 40 years, suggesting that they are evolving quickly to cope with a hotter, more variable climate. The work, led by Joel Kingsolver at UNC-Chapel Hill, represents a rare instance of how recent climate change affects physiological traits, such as how the body regulates feeding behavior. “To our knowledge, this is the first instance where we show changes in physiological traits in response to recent climate change,” says Kingsolver, Kenan Distinguished Professor of Biology in UNC’s College of Arts and Sciences, whose work appears today in the journal Functional Ecology. Caterpillars can eat and grow only when it’s not too cold and not too hot, explains Kingsolver. But when temperatures are ideal, caterpillars eat with reckless abandon and can gain up to 20 percent of their body weight in an hour. That growth determines their ability to survive, how quickly they become adult butterflies and their ultimate reproductive success. Jessica Higgins, a graduate student in Kingsolver’s lab who spearheaded the study, worked with fellow graduate student Heidi MacLean, Lauren Buckley, currently at the University of Washington, and Kingsolver to compare modern caterpillars to their ancestors from 40 years ago.

Their results show that the two related species of Colias (sulphur) butterflies have adapted in two ways: they not only broadened the range of their ideal feeding temperatures but also shifted their optimal feeding temperature to a higher one. In their work, the researchers measured changes in climate at the two study sites and then examined changes in how fast caterpillar ate using current and historical data from the 1970s, collected by Kingsolver’s graduate adviser Ward Watt. Although they found little change in the average air temperature at both study sites, they noticed that the frequency of hot temperatures — that is, temperatures that exceeded 82 degrees Fahrenheit -increased two-fold in Colorado and four-fold in California over the past 40 years. In response to these temperature fluctuations, modern caterpillars in Colorado ate faster at higher temperatures than their 1970s counterparts. In California, the modern caterpillars ate faster at both high and low temperatures than did their ancestors, but their optimal feeding temperatures did not change. “These two species of caterpillars adapted to the increased frequency of higher temperatures over 40 years in two different ways, but both are better suited than their ancestors to thrive in a hotter, more variable climate,” says Higgins. “Our climate is changing. The thermal physiology of these species is changing, too.”

Science Daily
January 21, 2014

Original web page at Science Daily

A comparison of standardized demographic patterns across 46 species, published in Nature, suggests that the vast diversity of ‘ageing strategies’ among them challenges the notion that evolution inevitably leads to senescence, or deterioration of mortality and fertility, with age, says Owen Jones, a biologist at the University of Southern Denmark in Odense, who led the study. “By taking a grand view and doing a survey across species, we found plenty of violations of this underpinning theory,” says Jones. To compare fertility and mortality patterns, the authors assembled published life-history data sets for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga, and standardized the trajectories — dividing mortality rates at each point in the lifespan by the average mortality rate. They found no association between the length of life and the degree of senescence. Of the 24 species showing the most abrupt increase in mortality with age, 11 had relatively long lifespans and 13 had relatively short lifespans. A similar split in lifespan occurred in the species that had a less abrupt increase in mortality.

When the researchers organized the species along a senescence continuum, mammals were clustered at one end of the spectrum, among the organisms that have an abrupt shift in mortality, and plants, which boast vastly lower relative mortality, populated the other end. Birds and invertebrates were scattered throughout. The authors suggest that the diversity of ageing strategies across the spectrum should challenge theoreticians. “The evolutionary theories we have are applicable in lots of situations — but they can’t explain some cases,” says Jones. “It’s not about throwing out old theories; it’s about modifying theories to work on all species.”

Nature
January 7, 2014

Original web page at Nature