Working with SFU chemist Robert Britton and a team of students, they have finally found the solution–a set of chemical attractants, or pheromones, that lure the bedbugs into traps, and keep them there.
This month, after a series of successful trials in bedbug-infested apartments in Metro Vancouver, they have published their research, “Bedbug aggregation pheromone finally identified,” in Angewandte Chemie, a general chemistry journal.
They’re working with Victoria-based Contech Enterprises Inc. to develop the first effective and affordable bait and trap for detecting and monitoring bedbug infestations. They expect it to be commercially available next year.
“The biggest challenge in dealing with bedbugs is to detect the infestation at an early stage,” says Gerhard, who holds an NSERC-Industrial Research Chair in Multimodal Animal Communication Ecology.
“This trap will help landlords, tenants, and pest-control professionals determine whether premises have a bedbug problem, so that they can treat it quickly. It will also be useful for monitoring the treatment’s effectiveness.”
It’s a solution the world has been waiting for.
Over the last two decades the common bedbug (Cimex lectularius), once thought eradicated in industrialized countries, has reappeared as a global scourge. These nasty insects are infesting not just low-income housing but also expensive hotels and apartments, and public venues such as stores, movie theatres, libraries and even public transit.
And while these blood-sucking pests were previously not considered a carrier of disease, scientists have recently discovered they can transmit the pathogen that causes Chagas disease, which is prevalent in Central and South America. Yet until now, tools for detecting and monitoring these pests have been expensive and technically challenging to use.
The research was funded with a Natural Sciences and Engineering Research Council of Canada industry grant in partnership with Contech Enterprises Inc.
Backgrounder: The research story–180,000 bedbug bites later
The Gries’ began their research eight years ago when Gerhard, who is internationally renowned for his pioneering work in chemical and bioacoustic communication between insects, began searching for pheromones that could lure and trap bedbugs.
Regine worked with him, running all of the lab and field experiments and, just as importantly, enduring 180,000 bedbug bites in order to feed the large bedbug colony required for their research. She became the unintentional “host” because, unlike Gerhard, she is immune to the bites, suffering only a slight rash instead of the ferocious itching and swelling most people suffer.
The Gries’ and their students initially found a pheromone blend that attracted bedbugs in lab experiments, but not in bedbug-infested apartments. “We realized that a highly unusual component must be missing–one that we couldn’t find using our regular gas chromatographic and mass spectrometric tools,” says Gerhard.
That’s when they teamed up with Britton, an expert in isolating and solving the structure of natural products, and then synthesizing them in the lab. He used SFU’s state-of-the-art NMR spectrometers to study the infinitesimal amounts of chemicals Regine had isolated from shed bedbug skin, looking for the chemical clues as to why the bedbugs find the presence of skin so appealing in a shelter.
It was like looking for a needle in a haystack.
After two years of frustrating false leads, Britton, his students and the Gries duo finally discovered that histamine, a molecule with unusual properties that eluded identification through traditional methods, signals “safe shelter” to bedbugs. Importantly, once in contact with the histamine, the bedbugs stay put whether or not they have recently fed on a human host.
Yet, to everyone’s disbelief, neither histamine alone nor in combination with the previously identified pheromone components effectively attracted and trapped bedbugs in infested apartments. So Regine began analyzing airborne volatile compounds from bedbug faeces as an alternate source of the missing components.
Five months and 35 experiments later, she had found three new volatiles that had never before been reported for bedbugs. These three components, together with two components from their earlier research and, of course, histamine, became the highly effective lure they were seeking.
Their research isn’t over yet, however. They continue to work with Contech Enterprises to finalize development of the commercial lure–which means Regine is still feeding the bedbugs every week. “I’m not too thrilled about this,” admits Regine, “but knowing how much this technology will benefit so many people, it’s all worth it.”
- Regine Gries, Robert Britton, Michael Holmes, Huimin Zhai, Jason Draper, Gerhard Gries. Bed Bug Aggregation Pheromone Finally Identified. Angewandte Chemie International Edition, 2014; DOI: 10.1002/anie.201409890
Simon Fraser University. “Putting bedbugs to bed forever.” ScienceDaily. ScienceDaily, 24 December 2014. <www.sciencedaily.com/releases/2014/12/141224103113.htm>.
When an egg cell is fertilised by a sperm, it begins to divide into a cluster of cells known as a blastocyst, the early stage of the embryo. Within this ball of cells, some cells form the inner cell mass — which will develop into the foetus — and some form the outer wall, which becomes the placenta. Cells in the inner cell mass are ‘reset’ to become stem cells — cells that have the potential to develop into any type of cell within the body. A small number of these cells become primordial germ cells (PGCs) — these have the potential to become germ cells (sperm and egg), which in later life will pass on the offspring’s genetic information to its own offspring.
“The creation of primordial germ cells is one of the earliest events during early mammalian development,” says Dr Naoko Irie, first author of the paper from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge. “It’s a stage we’ve managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells. It has highlighted important differences between embryo development in humans and rodents that may mean findings in mice and rats may not be directly extrapolated to humans.”
Professor Surani at the Gurdon Institute, who led the research, and his colleagues found that a gene known as SOX17 is critical for directing human stem cells to become PGCs (a stage known as ‘specification’). This was a surprise as the mouse equivalent of this gene is not involved in the process, suggesting a key difference between mouse and human development. SOX17 had previously been shown to be involved in directing stem cells to become endodermal cells, which then develop into cells including those for the lung, gut and pancreas, but this is the first time it has been seen in PGC specification.
The group showed that PGCs could also be made from reprogrammed adult cells, such as skin cells, which will allow investigations on patient-specific cells to advance knowledge of the human germline, infertility and germ cell tumours. The research also has potential implications for understanding the process of ‘epigenetic’ inheritance. Scientists have known for some time that our environment — for example, our diet or smoking habits — can affect our genes through a process known as methylation whereby molecules attach themselves to our DNA, acting like dimmer switches to increase or decrease the activity of genes. These methylation patterns can be passed down to the offspring.
Professor Surani and colleagues have shown that during the PGC specification stage, a programme is initiated to erase these methylation patterns, acting as a ‘reset’ switch. However, traces of these patterns might be inherited — it is not yet clear why this might occur.
“Germ cells are ‘immortal’ in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,” adds Professor Surani. “The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes ‘rejuvenation’ of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest towards understanding age-related diseases, which in part might be due to cumulative epigenetic mutations.”
- Naoko Irie, Leehee Weinberger, Walfred W.C. Tang, Toshihiro Kobayashi, Sergey Viukov, Yair S. Manor, Sabine Dietmann, Jacob H. Hanna, M. Azim Surani.SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate. Cell, 2014; DOI: 10.1016/j.cell.2014.12.013
University of Cambridge. “Egg and sperm race: Scientists create precursors to human egg and sperm.” ScienceDaily. ScienceDaily, 25 December 2014. <www.sciencedaily.com/releases/2014/12/141225143546.htm>.
James Hudziak, M.D., professor of psychiatry and director of the Vermont Center for Children, Youth and Families, and colleagues including Matthew Albaugh, Ph.D., and graduate student research assistant Eileen Crehan, call their study “the largest investigation of the association between playing a musical instrument and brain development.”
The research continues Hudziak’s work with the National Institutes of Health Magnetic Resonance Imaging (MRI) Study of Normal Brain Development. Using its database, the team analyzed the brain scans of 232 children ages 6 to 18.
As children age, the cortex — the outer layer of the brain — changes in thickness. In previous analysis of MRI data, Hudziak and his team discovered that cortical thickening or thinning in specific areas of the brain reflected the occurrence of anxiety and depression, attention problems, aggression and behavior control issues even in healthy kids — those without a diagnosis of a disorder or mental illness. With this study, Hudziak wanted to see whether a positive activity, such as music training, would influence those indicators in the cortex.
The study supports The Vermont Family Based Approach, a model Hudziak created to establish that the entirety of a young person’s environment — parents, teachers, friends, pets, extracurricular activities — contributes to his or her psychological health. “Music is a critical component in my model,” Hudziak says.
The authors found evidence they expected — that music playing altered the motor areas of the brain, because the activity requires control and coordination of movement. Even more important to Hudziak were changes in the behavior-regulating areas of the brain. For example, music practice influenced thickness in the part of the cortex that relates to “executive functioning, including working memory, attentional control, as well as organization and planning for the future,” the authors write.
A child’s musical background also appears to correlate with cortical thickness in “brain areas that play a critical role in inhibitory control, as well as aspects of emotion processing.”
The findings bolster Hudziak’s hypothesis that a violin might help a child battle psychological disorders even better than a bottle of pills. “We treat things that result from negative things, but we never try to use positive things as treatment,” he says.
Such an approach may prove difficult to accomplish. According to the study’s authors, research from the U.S. Department of Education indicates that three-quarters of U.S. high school students “rarely or never” take extracurricular lessons in music or the arts.
“Such statistics, when taken in the context of our present neuroimaging results,” the authors write, “underscore the vital importance of finding new and innovative ways to make music training more widely available to youths, beginning in childhood.”
- James Hudziak, M.D. et al. Cortical Thickness Maturation and Duration of Music Training: Health-Promoting Activities Shape Brain Development.Journal of American Academy of Child and Adolescent Psychiatry, December 2014 DOI: 10.1016/j.jaac.2014.06.015 show
University of Vermont. “Could playing Tchaikovsky’s ‘Nutcracker’ and other music improve kids’ brains?.” ScienceDaily. ScienceDaily, 23 December 2014. <www.sciencedaily.com/releases/2014/12/141223132546.htm>.
“This is the first study to show comparable safety and immune response of an experimental Ebola vaccine in an African population,” says lead author Dr Julie Ledgerwood from the National Institutes of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health, USA. “This is particularly encouraging because those at greatest risk of Ebola live primarily in Africa, and diminished vaccine protection in African populations has been seen for other diseases.”
Scientists from the NIAID developed the DNA vaccines that code for Ebola virus proteins from the Zaire and Sudan strains and the Marburg virus protein. The vaccines contain the construction plans for the proteins on the outer surface of the virus. Immune responses against these proteins have shown to be highly protective in non-human primate models.
In this phase 1 trial, the Makerere University Walter Reed Program enrolled 108 healthy adults aged between 18 and 50 from Kampala, Uganda between November, 2009 and April, 2010. Each volunteer was randomly assigned to receive an intramuscular injection of either the Ebola vaccine (30 volunteers), Marburg vaccine (30), both vaccines (30), or placebo (18) at the start of the study, and again 4 weeks and 8 weeks later.
The vaccines given separately and together were safe and stimulated an immune response in the form of neutralising antibodies and T-cells against the virus proteins. Four weeks after the third injection, just over half of the volunteers (57%; 17 of 30) had an antibody response to the Ebola Zaire protein as did 14 of 30 participants who received both the Ebola and Marburg vaccines. However, the antibodies were not long-lasting and returned to undetectable levels within 11 months of vaccination.
Both DNA vaccines were well tolerated in Ugandan adults with similar numbers of local and systemic reactions reported in all groups. Only one serious adverse event (neutropenia; low white blood cell count) was reported in a Marburg vaccine only recipient, but was not thought to be vaccine related.
According to Dr Ledgerwood, “These findings have already formed the basis of a more potent vaccine, delivered using a harmless chimpanzee cold virus, which is undergoing trials in the USA, UK, Mali, and Uganda in response to the ongoing Ebola virus outbreak.”
Writing in a linked Comment, Dr Saranya Sridhar from the Jenner Institute at the University of Oxford in the UK says, “[This] study deserves to be the focal point around which the broader question of vaccine development, particularly for Africa, must be addressed. With the uncharitable benefit of hindsight in view of the evolving 2014 Ebola outbreak, we must ask ourselves whether a filovirus vaccine should have been in more advanced clinical development. The international response to the present Ebola outbreak is an exemplar of the speed and purpose with which clinical vaccine development can progress and has set the benchmark against which future vaccine development must be judged. This study is the first step on the aspirational road towards the deployment of filovirus vaccines in Africa and must serve to shake the metaphorical cobwebs that can stall our advance towards this destination.”
- Hannah Kibuuka, Nina M Berkowitz, Monica Millard, Mary E Enama, Allan Tindikahwa, Arthur B Sekiziyivu, Pamela Costner, Sandra Sitar, Deline Glover, Zonghui Hu, Gyan Joshi, Daphne Stanley, Meghan Kunchai, Leigh Anne Eller, Robert T Bailer, Richard A Koup, Gary J Nabel, John R Mascola, Nancy J Sullivan, Barney S Graham, Mario Roederer, Nelson L Michael, Merlin L Robb, Julie E Ledgerwood. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. The Lancet, 2014; DOI: 10.1016/S0140-6736(14)62385-0
The Lancet. “Trial confirms Ebola vaccine candidate safe, equally immunogenic in Africa.” ScienceDaily. ScienceDaily, 23 December 2014. <www.sciencedaily.com/releases/2014/12/141223084000.htm>.
Although H2S gas is extremely toxic in high amounts, low levels present in naturally occurring sulfur springs have long been associated with health benefits. Mammalian cells also produce low levels of H2S, but this is the first time that this molecule has been linked directly to the health benefits of dietary restriction.
“This finding suggests that H2S is one of the key molecules responsible for the benefits of dietary restriction in mammals and lower organisms as well,” said senior author James Mitchell, associate professor of genetics and complex diseases. “While more experiments are required to understand how H2S exerts its beneficial effects, it does give us a new perspective on which molecular players to target therapeutically in our efforts to combat human disease and aging.”
The study appears online December 23, 2014 in Cell.
Dietary restriction is a type of intervention that can include reduced overall food intake, decreased consumption of particular macronutrients such as protein, or intermittent bouts of fasting. It is known to have beneficial health effects, including protection from tissue injury and improved metabolism. It has also been shown to extend the lifespan of multiple model organisms, ranging from yeast to primates. The molecular explanations for these effects are not completely understood, but were thought to require protective antioxidant responses activated by the mild oxidative stress caused by dietary restriction itself.
First author Christopher Hine, research fellow in the Department of Genetics and Complex Diseases, and colleagues demonstrated that one week of dietary restriction increased antioxidant responses and protected mice from liver ischemia reperfusion injury, but surprisingly, this protective effect was intact even in animals that could not mount such an antioxidant response. Instead, the researchers found that the protection required increased production of H2S, which occurred upon reduction of dietary intake of the two sulfur-containing amino acids, methionine and cysteine. When the diet was supplemented with these two amino acids, increased H2S production and dietary restriction benefits were both lost.
The investigators also found that genes involved in H2S production were also required for longevity benefits of dietary restriction in other organisms, including yeast, worms, and flies.
“These findings give us a better understanding of how dietary interventions extend lifespan and protect against injury. More immediately, they could have important implications for what to eat and not to eat before a planned acute stress like surgery, when the risk of ischemic injury can be relatively high,” said Hine.
- Christopher Hine, Eylul Harputlugil, Yue Zhang, Christoph Ruckenstuhl, Byung Cheon Lee, Lear Brace, Alban Longchamp, Jose H. Treviño-Villarreal, Pedro Mejia, C. Keith Ozaki, Rui Wang, Vadim N. Gladyshev, Frank Madeo, William B. Mair, James R. Mitchell. Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits. Cell, 2014; DOI:10.1016/j.cell.2014.11.048
Harvard School of Public Health. “Molecular mechanism behind health benefits of dietary restriction identified.” ScienceDaily. ScienceDaily, 23 December 2014. <www.sciencedaily.com/releases/2014/12/141223122220.htm>.
In this case, the parts are not resistors and capacitors, but 3-D microtissues containing thousands to millions of living cells that need a constant stream of fluid to bring them nutrients and to remove waste. The new device is called ‘BioP3’ for pick, place, and perfuse. A team of researchers led by Jeffrey Morgan, a Brown University bioengineer, and Dr. Andrew Blakely, a surgery fellow at Rhode Island Hospital and the Warren Alpert Medical School, introduces BioP3 in a new paper in the journal Tissue Engineering Part C.
Because it allows assembly of larger structures from small living microtissue components, Morgan said, future versions of BioP3 may finally make possible the manufacture of whole organs such as livers, pancreases, or kidneys.
“For us it’s exciting because it’s a new approach to building tissues, potentially organs, layer by layer with large, complex living parts,” said Morgan, professor of molecular pharmacology, physiology and bBiotechnology. “In contrast to 3-D bioprinting that prints one small drop at a time, our approach is much faster because it uses pre-assembled living building parts with functional shapes and a thousand times more cells per part.”
Morgan’s research has long focused on making individual microtissues in various shapes such as spheres, long rods, donut rings and honeycomb slabs. He uses a novel micromolding technique to direct the cells to self-assemble and form these complex shapes. He is a founder of the Providence startup company MicroTissues Inc., which sells such culture-making technology.
Now, the new paper shows, there is a device to build even bigger tissues by combining those living components.
“This project was particularly interesting to me since it is a novel approach to large-scale tissue engineering that hasn’t been previously described,” Blakely said.
The BioP3 prototype
The BioP3, made mostly from parts available at Home Depot for less than $200, seems at first glance to be a small, clear plastic box with two chambers: one side for storing the living building parts and one side where a larger structure can be built with them. It’s what rests just above the box that really matters: a nozzle connected to some tubes and a microscope-like stage that allows an operator using knobs to precisely move it up, down, left, right, out and in.
The plumbing in those tubes allows a peristaltic pump to create fluid suction through the nozzle’s finely perforated membrane. That suction allows the nozzle to pick up, carry and release the living microtissues without doing any damage to them, as shown in the paper.
Once a living component has been picked, the operator can then move the head from the picking side to the placing side to deposit it precisely. In the paper, the team shows several different structures Blakely made including a stack of 16 donut rings and a stack of four honeycombs. Because these are living components, the stacked microtissues naturally fuse with each other to form a cohesive whole after a short time.
Because each honeycomb slab had about 250,000 cells, the stack of four achieved a proof-of-concept, million-cell structure more than 2 millimeters thick.
That’s not nearly enough cells to make an organ such as a liver (an adult’s has about 100 billion cells), Morgan said, but the stack did have a density of cells consistent with that of human organs. In 2011, Morgan’s lab reported that it could make honeycomb slabs 2 centimeters wide, with 6 million cells each. Complex stacks with many more cells are certainly attainable, Morgan said.
If properly nurtured, stacks of these larger structures could hypothetically continue to grow, Morgan said. That’s why the BioP3 keeps a steady flow of nutrient fluid through the holes of the honeycomb slabs to perfuse nutrients and remove waste. So far, the researchers have shown that stacks survive for days.
In the paper the team made structures with a variety of cell types including H35 liver cells, KGN ovarian cells, and even MCF-7 breast cancer cells (building large tumors could have applications for testing of chemotherapeutic drugs or radiation treatments). Different cell types can also be combined in the microtissue building parts. In 2010, for example, Morgan collaborated on the creation of an artificial human ovary unifying three cell types into a single tissue.
Because version 1.0 of the BioP3 is manually operated, it took Blakely about 60 minutes to stack the 16 donut rings around a thin post, but he and Morgan have no intention of keeping it that way.
In September, Morgan received a $1.4-million, three-year grant from the National Science Foundation in part to make major improvements, including automating the movement of the nozzle to speed up production.
“Since we now have the NSF grant, the Bio-P3 will be able to be automated and updated into a complete, independent system to precisely assemble large-scale, high-density tissues,” Blakely said.
In addition, the grant will fund more research into living building parts — how large they can be made and how they will behave in the device over longer periods of time. Those studies include how their shape will evolve and how they function as a stack.
“We are just at the beginning of understanding what kinds of living parts we can make and how they can be used to design vascular networks within the structures,” Morgan said. “Building an organ is a grand challenge of biomedical engineering. This is a significant step in that direction.”
Brown has sought a patent on the BioP3.
In addition to Blakely and Morgan, the paper’s other authors are biology graduate student Kali Manning and Anubhav Tripathi, profesor of engineering, who co-directs Brown’s Center for Biomedical Engineering with Morgan.
The National Institutes of Health (grant T32 GM065085-09) and the NSF (grant CBET-1428092) have supported the research.
- Andrew M. Blakely, Kali L. Manning, Anubhav Tripathi, Jeffrey R. Morgan. Bio-Pick, Place, and Perfuse: A New Instrument for 3D Tissue Engineering. Tissue Engineering Part C: Methods, 2014; 141220021855001 DOI:10.1089/ten.TEC.2014.0439
Brown University. “New technology makes tissues, someday maybe organs.” ScienceDaily. ScienceDaily, 22 December 2014. <www.sciencedaily.com/releases/2014/12/141222111649.htm>.
The first SPICAM (Spectroscopy for Investigation of Characteristics of the Atmosphere of Mars) instrument was built for the Russian Martian orbiter Mars 96, which was lost due to an accident in the rocket launcher.
The new updated version of the instrument was built with the participation of the Space Research Institute as part of the agreement between RosCosmos and the French space agency CNES for the Mars Express orbiter. The apparatus was launched on June 2, 2003 from the Baikonur Cosmodrome using a Russian Soyuz rocket launcher with a Fregat propulsion stage. At the end of December 2003, Mars Express entered a near-Mars orbit and since then has been operating successfully, collecting data on the planet and its surroundings.
Staff of the Space Research Institute and MIPT, including Alexander Trokhimovsky, Anna Fyodorova, Oleg Korablyov and Alexander Rodin, together with their colleagues from the French laboratory LATMOS and NASA’s Goddard Center, have analysed a mass of data obtained by observing water vapour in Mars’ atmosphere using an infrared spectrometer that is part of the SPICAM instrument over a period of five Martian years (about 10 Earth years as a year on Mars is equal to 1.88 Earth years).
Conditions on Mars — low temperatures and low atmospheric pressure — do not allow water to exist in liquid form in open reservoirs as it would on Earth. However, on Mars, there is a powerful layer of permafrost, with large reserves of frozen water concentrated at the polar caps. There is water vapour in the atmosphere, although at very low levels compared to the quantities experienced hereon Earth. If the entire volume of water in the atmosphere was to be spread evenly over the surface of the planet, the thickness of the water layer would not exceed 10-20 microns, while on Earth such a layer would be thousands of times thicker.
Data from the SPICAM experiment has allowed scientists to create a picture of the annual cycle of water vapour concentration variation in the atmosphere. Scientists have been observing the atmosphere during missions to Mars since the end of the 1970s in order to make the picture more precise, as well as traceits variability.
The content of water vapour in the atmosphere reaches a maximum level of 60-70 microns of released water in the northern regions during the summer season. The summer maximum in the southern hemisphere is significantly lower — about 20 microns. The scientists have also established a significant, by 5-10 microns, reduction in the concentration of water vapour during global sandstorms, which is probably connected to the removal of water vapour from the atmosphere due to adsorption processes and condensation on surfaces.
“This research, based on one of the longest periods of monitoring of the Martian climate, has made an important contribution to the understanding of the Martian hydrological cycle — the most important of the climate mechanisms which could potentially support the existence of biological activity on the planet,” said co-author of the research Alexander Rodin, deputy head of the Infrared Spectroscopy of Planetary Atmospheres Laboratory at MIPT and senior scientific researcher at the Space Research Institute.
- Alexander Trokhimovskiy, Anna Fedorova, Oleg Korablev, Franck Montmessin, Jean-Loup Bertaux, Alexander Rodin, Michael D. Smith. Mars’ water vapor mapping by the SPICAM IR spectrometer: Five martian years of observations.Icarus, 2014; DOI: 10.1016/j.icarus.2014.10.007
Moscow Institute of Physics and Technology. “Scientists ‘map’ water vapor in Martian atmosphere.” ScienceDaily. ScienceDaily, 22 December 2014. <www.sciencedaily.com/releases/2014/12/141222111603.htm>.
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“Our data add additional important support to the hypothesis that maternal exposure to air pollution contributes to the risk of autism spectrum disorders,” said Marc Weisskopf, associate professor of environmental and occupational epidemiology and senior author of the study. “The specificity of our findings for the pregnancy period, and third trimester in particular, rules out many other possible explanations for these findings.”
The study appears online December 18, 2014 inEnvironmental Health Perspectives.
Prior studies have suggested that, in addition to genetics, exposure to airborne environmental contaminants, particularly during pregnancy and early life, may affect risk of autism. This study focused specifically on the pregnancy period.
The study population included offspring of participants living in all 50 states in Nurses’ Health Study II, a cohort of more than 116,000 female U.S. nurses begun in 1989. The researchers collected data on where participants lived during their pregnancies as well as data from the U.S. Environmental Protection Agency and other sources on levels of fine particulate matter air pollution (PM2.5)–particles 2.5 microns in diameter or smaller–in locations across the U.S. The researchers identified 245 children who were diagnosed with autism spectrum disorder (ASD) and a control group of 1,522 children without ASD during the time period studied.
The researchers explored the association between autism and exposure to PM2.5 before, during, and after pregnancy. They also calculated exposure to PM2.5 during each pregnancy trimester.
Exposure to PM2.5 was significantly associated with autism during pregnancy, but not before or after, the study found. And during the pregnancy, the third trimester specifically was significantly associated with an increased risk. Little association was found between air pollution from larger-sized particles (PM10-2.5) and autism.
“The evidence base for a role for maternal exposure to air pollution increasing the risk of autism spectrum disorders is becoming quite strong,” said Weisskopf. “This not only gives us important insight as we continue to pursue the origins of autism spectrum disorders, but as a modifiable exposure, opens the door to thinking about possible preventative measures.”
- Marc Weisskopf et al. Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort. Environmental Health Perspectives, December 2014 DOI: 10.1289/ehp.1408133
Harvard School of Public Health. “Fine particulate air pollution linked with increased autism risk.” ScienceDaily. ScienceDaily, 18 December 2014. <www.sciencedaily.com/releases/2014/12/141218081334.htm>.
The researchers think these instances of introgressive hybridization — a way for genetic material and, potentially, traits to be passed from one species to another through interspecific mating — are only the first of many needles waiting to be found in a very large genetic haystack. While introgressive hybridization is thought to be common among plants, the finding suggests that hybridization in mammals may not be the evolutionary dead end biologists once commonly thought.
Rice biologist Michael Kohn and computer scientist Luay Nakhleh reported that two species of mice from various locations in Europe and Africa have shared genetic code to their apparent evolutionary advantage at least three times over the centuries.
Kohn, who tracks the genetic roots of mice to see how favorable evolutionary traits develop, and Nakhleh, who studies evolution by comparing genomic data, shared their findings this week in the Proceedings of the National Academy of Sciences.
Mice are common subjects for evolutionary studies of mammals because they breed quickly and a biologist can follow many generations in the span of one’s career. The ability to track such interactions has implications for human genetics and health, the researchers said.
Kohn previously detailed a mutation in common European house mice (Mus musculus domesticus) that gave them resistance to warfarin, a rodent poison also used as a blood thinner in humans. Evidence indicated the mutation appeared in mice about 10 years after the introduction of warfarin and seemed connected to geographically distant Algerian mice (Mus spretus) that carried the same mutation.
But that project looked at only small sections of the mouse genome on one chromosome where the mutant gene in question, Vkorc1, was known to exist. “That gene had adaptively introgressed between these mice and was known to cause resistance at a time when some scientists thought such events should not happen,” said Kohn, an associate professor of ecology and evolutionary biology.
“The question then became, Is it rare or is it common? With the approach we used in this paper, we now know it’s not unique,” he said. The new study compares genome-scale data of 21 mice that originated in 15 different locations in Europe and Africa.
Kohn, Nakhleh and lead author Kevin Liu, their former postdoctoral researcher and now an assistant professor at Michigan State University, employed Rice’s supercomputers and the Nakhleh lab’s open-source PhyloNet-HMM software to locate statistically likely connections between the re-sequenced complete genomes, some newly determined and some collected previously in a massive effort to understand the evolutionary origins of the laboratory mouse genome.
They turned up two more sets of genomic regions, or tracts, that showed hybridization events; one appears to predate the colonization of Europe by M. m. domesticus, and the other affected the subjects’ sense of smell — a definite evolutionary advantage for mice looking for food or mates. “That’s apparently an important locus,” Kohn said.
“The category that jumped out was the olfactory genes,” said Nakhleh, an associate professor of computer science and of biosciences, who had been thinking about large-scale studies of the mouse genome with Kohn since both arrived at Rice in 2004. “Now one has to work through the biology to figure out how this hybridization happened.”
“The new statistical method developed in Luay’s group can only tell you whether an event is there or not. It cannot tell you why it’s there or what it does. But it gives you a way to start looking,” Kohn added.
He said the lengths of the shared genomic tracts provide the key to estimating their ages and evolutionary dynamics. The longer the region, the more recently the hybridization event occurred. And some may be “driver genes” that drag along adjacent chunks of DNA. “One challenge is to see which are driver genes, meaning they encode a biological function that could be favored by natural selection, and which are just tagging along,” he said.
Kohn expects future studies will show evidence of more hybridization among mice from the regions studied and farther afield, though he also realizes many events will never be found.
“Hybrids don’t always pass the test imposed by evolution and disappear from the record,” he said. “We cannot measure them, because we can’t count what we can’t see.”
Nakhleh said other studies may have missed evidence of hybridization because the researchers weren’t specifically looking for it. “Why is it that biologists in general who look at mammalian genomes haven’t found hybridization? I think it’s because they started with the hypothesis that it couldn’t be there and used tools that would ignore it.
“This paper shows the value of collaboration between biologists and ‘big-data’ scientists,” he said. “It also shows there is a need to develop more sophisticated computational methods for biologists.”
Co-authors of the paper are Rice undergraduate students Ethan Steinberg and Alexander Yozzo and former Rice postdoctoral researcher Ying Song, now at the Chinese Academy of Agricultural Sciences in Beijing.
The National Institutes of Health’s National Heart, Lung and Blood Institute and National Library of Medicine, the National Science Foundation (NSF) and the Keck Center of the Gulf Coast Consortia supported the research. The researchers utilized the NSF-funded DAVinCi supercomputer administered by Rice’s Ken Kennedy Institute for Information Technology.
- Kevin J. Liu, Ethan Steinberg, Alexander Yozzo, Ying Song, Michael H. Kohn, Luay Nakhleh. Interspecific introgressive origin of genomic diversity in the house mouse. Proceedings of the National Academy of Sciences, 2014; 201406298 DOI: 10.1073/pnas.1406298111
Rice University. “Big-data analysis reveals gene sharing in mice.” ScienceDaily. ScienceDaily, 16 December 2014. <www.sciencedaily.com/releases/2014/12/141216175746.htm>.