A large international consortium of researchers has produced the first comprehensive, detailed map of the way genes work across the major cells and tissues of the human body. The findings describe the complex networks that govern gene activity, and the new information could play a crucial role in identifying the genes involved with disease.
There have been multiple plagues throughout history around the world, but none have been so deadly as the Black Death, which killed an estimated one in every four Europeans, and so exerted very strong selection. The Black Death didn’t just wipe out millions of Europeans during the 14th century. It left a mark on the human genome, favoring those who carried certain immune system genes, according to a new study. Those changes may help explain why Europeans respond differently from other people to some diseases and have different susceptibilities to autoimmune disorders.
Geneticists know that human populations evolve in the face of disease. Certain versions of our genes help us fight infections better than others, and people who carry those genes tend to have more children than those who don’t. So the beneficial genetic versions persist, while other versions tend to disappear as those carrying them die. This weeding-out of all but the best genes is called positive selection. But researchers have trouble pinpointing positively selected genes in humans, as many genes vary from one individual to the next.
Genetically, the Rroma gypsies in Romania are still quite similar to the northwestern Indians, even though they have lived side by side with the Romanians for a millennium, the team found. But there were 20 genes in the Rroma and the Romanians that had changes that were not seen in the Indians’ versions of those genes, Netea and his colleagues report online today in the Proceedings of the National Academy of Sciences. These genes “were positively selected for in the Romanians and in the gypsies but not in the Indians,” Netea explains. “It’s a very strong signal.”
Those genes included one for skin pigmentation, one involved in inflammation, and one associated with susceptibility to autoimmune diseases such as rheumatoid arthritis. But the ones Netea and Bertranpetit were most excited about were a cluster of three immune system genes found on chromosome 4. These genes code for toll-like receptors, proteins which latch on to harmful bacteria in the body and launch a defensive response. “We knew they must be important for host defense,” Netea says.
What events in history might have favored these versions of the genes in gypsies and Romanians, but not in Indians? Netea and his colleagues tested the ability of the toll-like receptors to react to Yersinia pestis, the bacterium that caused the Black Death. They found that the strength of the immune response varied depending on the exact sequence of the toll-like receptor genes.
Netea and Bertranpetit propose that the Rroma and European Romanians came to have the same versions of these immune system genes because of the evolutionary pressure exerted by Y. pestis. Other Europeans, whose ancestors also faced and survived the Black Death, carried similar changes in the toll-like receptor genes. But people from China and Africa—two other places the Black Death did not reach—did not have these changes. The similarities in the other genes were likely caused by other conditions experienced by Rroma and Europeans, but not Indians.
Navigate the brain in a way that was never before possible; fly through major brain pathways, compare essential circuits, zoom into a region to explore the cells that comprise it, and the functions that depend on it.The Human Connectome Project aims to provide an unparalleled compilation of neural data, an interface to graphically navigate this data and the opportunity to achieve never before realized conclusions about the living human brain.References:
- - Director of NIH Praises the Human Connectome Project - Muse’s latest album uses a Human Connectome Project rendering of white matter tracks. - Human Connectome Project pieces together neural data through brain scans - Brain Mapping Center Seminar Series: “Discovering the Human Connectome” - Mapping out a new era in brain research – CNN Labs - Probing the Brain’s Mysteries – The Wall Street Journal - First public release of 3T Connectom scanner data! - Connectom Scanner Uses Ultra-High Gradient Strength - Brain Mapping Seminar Series - First Images on the Connectom 3T Scanner Obtained
Scientists from Yale and Harvard have recoded the entire genome of an organism and improved a bacterium’s ability to resist viruses, a dramatic demonstration of the potential of rewriting an organism’...
A surgeon at The Ohio State University Wexner Medical Center is the first in the United States to consult with a distant colleague using live, point-of-view video from the operating room via Google Glass, a head-mounted computer and camera device.
“It’s a privilege to be a part of this project as we explore how this exciting new technology might be incorporated into the everyday care of our patients,” said Dr. Christopher Kaeding, the physician who performed the surgery and director of sports medicine at Ohio State. “To be honest, once we got into the surgery, I often forgot the device was there. It just seemed very intuitive and fit seamlessly.”
Google Glass has a frame similar to traditional glasses, but instead of lenses, there is a small glass block that sits above the right eye. On that glass is a computer screen that, with a simple voice command, allows users to pull up information as they would on any other computer. Attached to the front of the device is a camera that offers a point-of-view image and the ability to take both photos and videos while the device is worn.
During this procedure at the medical center’s University East facility, Kaeding wore the device as he performed ACL surgery on Paula Kobalka, 47, from Westerville, Ohio, who hurt her knee playing softball. As he performed her operation at a facility on the east side of Columbus, Google Glass showed his vantage point via the internet to audiences miles away.
Across town, one of Kaeding’s Ohio State colleagues, Dr. Robert Magnussen, watched the surgery his office, while on the main campus, several students at The Ohio State University College of Medicine watched on their laptops.
“To have the opportunity to be a medical student and share in this technology is really exciting,” said Ryan Blackwell, a second-year medical student who watched the surgery remotely. “This could have huge implications, not only from the medical education perspective, but because a doctor can use this technology remotely, it could spread patient care all over the world in places that we don’t have it already.”
“As an academic medical center, we’re very excited about the opportunities this device could provide for education,” said Dr. Clay Marsh, chief innovation officer at The Ohio State University Wexner Medical Center. “But beyond, that, it could be a game-changer for the doctor during the surgery itself.”
Experts have theorized that during surgery doctors could use voice commands to instantly call up x-ray or MRI images of their patient, pathology reports or reference materials. They could collaborate live and face-to-face with colleagues via the internet, anywhere in the world.
“It puts you right there, real time,” said Marsh, who is also the executive director of the Center for Personalized Health Care at Ohio State. “Not only might you be able to call up any kind of information you need or to get the help you need, but it’s the ability to do it immediately that’s so exciting,” he said. “Now, we just have to start using it. Like many technologies, it needs to be evaluated in different situations to find out where the greatest value is and how it can impact the lives of our patients in a positive way.”
Only 1,000 people in the United States have been chosen to test Google Glass as part of Google’s Explorer Program. Dr. Ismail Nabeel, an assistant professor of general internal medicine at Ohio State applied and was chosen. He then partnered with Kaeding to perform this groundbreaking surgery and to help test technology that could change the way we see medicine in the future.
The CSIRO scientists' role in the project was to establish how to prevent viruses reproducing in cells in the laboratory. They looked at the virus' resistance to existing drugs to establish that the new drug would work against the resistant viruses.
A crowdsourcing initiative to find a cure for drug-resistant malaria has been unveiled by Scripps Research Institute and IBM. The project, to be partly funded by money won from the Jeopardy!game show by IBM’s Watson computing system, has invited the public to volunteer their computers for use when idle through the World Community Grid (WCG).
The project, “Go Fight Against Malaria,” will use the WCG to compute numbers and perform simulations. Currently, 575,000 people in over 80 countries have volunteered around 2 million PCs to the WCG.
Working on malaria started as a hobby that I advanced during nights and weekends for a couple years, when I wasn’t working on FightAIDS@Home. With persistence and a lot of help from IBM and from fellow Scripps Research scientists, we are now ready to launch the largest computational research project ever performed against drug-resistant malaria.
The WCG crowd computers will use idle time when the PCs are not being used by their owners to compute small allocated tasks. Scientists will thus benefit from whatever outcomes the system gives by using the data to find cures for diseases, clean energy research or developing healthier foods.
From the increased computing power, the Scripps Research scientists are hoping the WCG will help compress 100 years of computations needed for such a venture into just one year. Data from crowd PCs will be used by scientists to study numerous compounds that can potentially help develop a cure for drug-resistant strains of malaria. The results of the experiments will be availed to the public.
A new era of science is upon us. Unlike before now when science relied on basic microscopy to illuminate cells that were previously too blurry to imagine what was actually going on inside. Now with the help of high-speed imagery, and fluorescent emissions microscopy, we can see exactly what is going on in the underpinnings of life by breaking the diffusion barrier.
Microscopes were first invented in 1590 by two eyeglass makers later to have the term, “Microscope” coined by Giovanni Faber coined the name microscope for Galileo Galilei‘s compound microscope in 1625. We now commonly use the modern light microscope that we’ve all probably played with at some point in our early schooling.
The issue with modern light microscopes is the fact that when looking at cells they are blurry. Further, more complex microscopes such as electron microscopes is the fact that there is a great deal of preparation in order to look at something. Generally something has to be suspended in formaldehyde, or plated in gold.
Now with the recent breakthrough in microscopy we can see exactly what is going on in a cell. Previously, the diffusion barrier warped light around cells giving them a lensed effect just like when looking at a cluster galaxy with a black hole in front of it (lensing effect). The significance of this break through is the fact that we now know for certain which processes are happening when we are looking inside of a cell.
In 8 May 1980, the World Health Organisation declared that “the world and its peoples are free from smallpox.” Through decades of intense vaccination, this once fatal disease had been wiped out. It was a singular victory and having won it, countries around the world discontinued the vaccination programmes. After all, why protect against a disease that no longer exists, except in a few isolated stocks?
Unfortunately, this is not a rhetorical question. The smallpox vaccine did more than protect against smallpox. It also reduced the risk of contracting a related illness called monkeypox, which produces the same combination of scabby bumps and fever. It’s milder than smallpox but it’s still a serious affliction. In Africa, where monkeypox originates from, it kills anywhere from 1-10% of those who are infected. And more and more people are becoming infected.
Anne Rimoin from the University of California, Los Angeles compared data on the virus in the Democratic Republic of Congo over the last three decades. She found that, during those years, monkeypox has become 20 times more common in humans. In one particular area, 72 people out of every million were infected each year between 1981 and 1986. Between 2005 and 2007, that figure rose to 1442 per million. Rimoin thinks that we eased up the pressure on smallpox vaccination too soon. Between 1981 and 1985, only 404 cases turned up in all of Africa, and simulations predicted that the disease was unlikely to spread too far in a human population before dying out. This was no public health threat. In 1986, even the monitoring programme was stopped. In 2005 however, Rimoin’s group, together with the DRC Ministry of Health and the World Health Organization set up a new round of monkeypox surveillance and they spent two years collecting data. Their research showed that the disease is gaining ground.
Rimoin found that monkeypox was disproportionately affecting children and almost all of those who fell sick were born after 1980, when the smallpox vaccination programme was halted in the DRC. The vaccine wasn’t a perfect defence against monkeypox but it was still around 85% effective. Among people who were born during the vaccination era, those who were immunised were 5 times less likely to develop monkeypox than their protected peers. And this protection is clearly long-lasting; even 25 years on, they could still ward off the related virus.
These figures are probably underestimates too. The region’s inconsistent healthcare isn’t exactly conducive to accurate disease monitoring and Rimoin says that her team had word of many more cases, but couldn’t always check them out because of their remote location.
Monkeypox is spread by animals including squirrels and, fairly obviously, monkeys. As humans encroach upon the DRC’s tropical rainforests, the risk of being exposed to an infected carrier grows. Indeed, Rimoin found that the odds of contracting monkeypox were higher for people living near forested areas, and for men. As civil strife continues to affect the DRC, locals are being forced to rely more on hunting to get enough food and that brings men in close contact with furry viral reservoirs.
It’s an emerging threat, but Rimoin isn’t calling for smallpox vaccination to resume. Doing so would be logistically difficult in an area where even collecting data can be fraught. It might be better to take a more targeted approach, vaccinating only health workers who treat infected patients, and people who come into frequent contact with animal carriers. It may also be worth educating local people about the dangers of handling carrier species and the benefits of isolating people who show the very obvious symptoms, until they can be treated.
But most importantly, Rimoin wants active surveillance in regions where the virus circulates, especially since there are still so many unknowns about the virus. We need to better understand how it moves from human to human (and from animal to human), how often it’s fatal, or what the complications are.
It’s a good opportunity to take action now, at a time when the monkeypox is still confined to specific areas. Things might not stay that way. In 2003, there was a bizarre outbreak in the United States, as rodents from Ghana brought the disease to American prairie dogs, who handed it over to humans. All sorts of rodents the world over might become reservoirs for the disease and Rimoin writes, “If monkeypox were to become established in a wildlife reservoir outside Africa, the public health setback would be difficult to reverse.”
Take a swab of saliva from your mouth and within minutes your DNA could be ready for analysis and genome sequencing with the help of a new device.
University of Washington engineers and NanoFacture, a Bellevue, Wash., company, have created a device that can extract human DNA from fluid samples in a simpler, more efficient and environmentally friendly way than conventional methods.
The device will give hospitals and research labs a much easier way to separate DNA from human fluid samples, which will help with genome sequencing, disease diagnosis and forensic investigations.
“It’s very complex to extract DNA,” said Jae-Hyun Chung, a UW associate professor of mechanical engineering who led the research. “When you think of the current procedure, the equivalent is like collecting human hairs using a construction crane.”
This technology aims to clear those hurdles. The small, box-shaped kit now is ready for manufacturing, then eventual distribution to hospitals and clinics. NanoFacture, a UW spinout company, signed a contract with Korean manufacturer KNR Systems last month at aceremony in Olympia, Wash.
The UW, led by Chung, spearheaded the research and invention of the technology, and still manages the intellectual property. Separating DNA from bodily fluids is a cumbersome process that’s become a bottleneck as scientists make advances in genome sequencing, particularly for disease prevention and treatment. The market for DNA preparation alone is about $3 billion each year.
Conventional methods use a centrifuge to spin and separate DNA molecules or strain them from a fluid sample with a micro-filter, but these processes take 20 to 30 minutes to complete and can require excessive toxic chemicals.
UW engineers designed microscopic probes that dip into a fluid sample – saliva, sputum or blood – and apply an electric field within the liquid. That draws particles to concentrate around the surface of the tiny probe. Larger particles hit the tip and swerve away, but DNA-sized molecules stick to the probe and are trapped on the surface. It takes two or three minutes to separate and purify DNA using this technology.
Bonnie Bassler discovered that bacteria "talk" to each other, using a chemical language that lets them coordinate defense and mount attacks. The find has stunning implications for medicine, industry -- and our understanding of ourselves.
Darwin referred to the origin of species as "that mystery of mysteries," and even today, more than 150 years later, evolutionary biologists cannot fully explain how new animals and plants arise.
For decades, nearly all research in the field has been based on the assumption that the main cause of the emergence of new species, a process called speciation, is the formation of barriers to reproduction between populations.
Those barriers can be geographic -- such as a new mountain, river or glacier that physically separates two populations of animals or plants -- or they can be genetic differences that prevent incompatible individuals from producing fertile offspring. A textbook example of the latter is the mule; horses and donkeys can mate, but their offspring are sterile.
But now a University of Michigan biologist and a colleague are questioning the long-held assumption that genetic reproductive barriers, also known as reproductive isolation, are a driving force behind speciation.
"Most research on the formation of species has assumed that these types of reproductive barriers are a major cause of speciation. But our results provide no support for this, and our study is actually the first direct test of how these barriers affect the rate at which species form," said Daniel Rabosky, assistant professor in the U-M Department of Ecology and Evolutionary Biology and a curator of herpetology at the Museum of Zoology.
Rabosky and Daniel Matute of the University of Chicago reasoned that if genetic barriers to reproduction are a leading cause of new species, then groups of organisms that quickly accumulate those genes should also show high rates of species formation.
They tested that idea by comparing speciation rates to genetic indicators of reproductive isolation in birds and fruit flies. They chose birds and fruit flies because extensive data sets on interspecies breeding experiments exist for both groups. The researchers used evolutionary tree-based estimates of speciation rates for nine major fruit fly groups and two-thirds of known bird species.
Rabosky and Matute created computer models to carry out the comparison, and the results surprised them. "We found no evidence that these things are related. The rate at which genetic reproductive barriers arise does not predict the rate at which new species form in nature," Rabosky said. "If these results are true more generally -- which we would not yet claim but do suspect -- it would imply that our understanding of species formation is extremely incomplete because we've spent so long studying the wrong things, due to this erroneous assumption that the main cause of species formation is the formation of barriers to reproduction.
"To be clear, reproductive barriers are still important on some level. All sorts of plants and animals live together in the same place, which couldn't happen without reproductive barriers. But our results question whether genetic reproductive barriers played a major role in how those species formed in the first place."
While speciation is often defined as the evolution of reproductive isolation, the new findings suggest that a broader definition may be needed, Rabosky and Matute conclude.
By mimicking a technique used by an intestinal parasite of fish, researchers have developed a flexible patch studded with microneedles that holds skin grafts in place more strongly than surgical staples do. After burrowing into the walls of a fish's intestines, the spiny-headed worm Pomphorhynchus laevis inflates its proboscis to better embed itself in the soft tissue. In the new patch (sample shown in main image), the stiff polystyrene core of the 700-micrometer-tall needles (inset) penetrates the tissue; then a thin hydrogel coating on the tip of each needle—a coating based on the material in disposable diapers that expands when it gets wet—swells to help anchor the patch in place. In tests using skin grafts, adhesion strength of the patch was more than three times higher than surgical staples, the researchers report online today in Nature Communications. Because the patch doesn't depend on chemical adhesives for its gripping power, there's less chance for patients to have an allergic reaction. And because the microneedles are about one-quarter the length of typical surgical staples, the patches cause less tissue damage when they're removed, the researchers contend. Besides holding grafts in place, the patch could be used to hold the sides of a wound or an incision together—even, in theory, ones inside the body if a slowly dissolving version of the patch can be developed. Moreover, the researchers say, the hydrogel coating holds promise as a way to deliver proteins, drugs, or other therapeutic substances to patients.
Eye color is much more complicated than is usually taught in high school (or presented in The Tech’s eye color calculator). There we learn that two genes influence eye color. One gene comes in two versions, brown (B) and blue (b). The other gene comes in green (G) and blue (b). All eye color and inheritance was thought to be explained by this simple model. Except of course for the fact that it is obviously incomplete.
The model cannot, for example, explain how blue eyed parents can have a brown eyed child. Yet this can and does happen (although it isn’t common).
New research shows that the first gene is actually two separate genes, OCA2 and HERC2. In other words, there are two ways to end up with blue eyes.
Normally this wouldn’t be enough to explain how blue eyed parents can have a brown eyed child. Because of how eye color works (see below), if one gene can cause brown eyes, it would dominate over another that causes blue. In fact, that is what happens with green eyes in the older model. The brown gene dominates over the green one resulting in brown eyes.
The key is that if someone makes a lot of pigment in the front part of their eye, they have brown eyes. And if they make none there, they have blue.
Part of the pigment making process involves OCA2 and HERC2. A working HERC2 is needed to turn on OCA2 and OCA2 helps to actually get the pigment made. They need each other to make pigment.
So someone with only broken HERC2 genes will have blue eyes no matter what OCA2 says. This is because the working OCA2 can't be turned on so no pigment gets made.
And the opposite is true as well. Someone with broken OCA2 genes will have blue eyes no matter what the HERC2 genes are. Turning on a broken pigment making gene still gives you no pigment. You need a working HERC2 and a working OCA2 to have brown eyes.
Because the two genes depend on each other, it is possible for someone to actually be a carrier of a dominant trait like brown eyes. And if two blue eyed parents are carriers, then they can have a brown eyed child.
Scientists know that climate change is putting species around the globe in peril, but just how much peril? After all, when evolution failed to keep pace with a major climatic event 65 million years ago, half the planet's species went extinct and dinosaurs were reduced to jittery feathered creatures that get bullied by squirrels on bird-feeders. A new study suggests that our current era of climate change won't just exceed the rate of evolution, but will do so by a factor of thousands. Although the work doesn't go so far as predicting an extinction rate, it doesn't bode well for the near future of global biodiversity.
The world has warmed 0.6°C in the past few decades, and climate models say that we could see another 4° by century's end. "We want to know if species will be able to adapt to climate change quickly enough based on how they adapted to climate change in the past," says evolutionary ecologist John Wiens, of the University of Arizona in Tucson, and lead author of the new study. Wiens decided to investigate by looking at the top branches of family trees.
When two living species are closely related, scientists can estimate how long ago they diverged, thus providing an age for their common ancestor. Researchers can also estimate temperature and precipitation in that ancestor's habitat, using evolutionary models. With help from Yale University biology student Ignacio Quintero, Wiens calculated such estimates for 540 species in 17 groups of living vertebrates. They studied reptiles, amphibians, birds, and mammals primarily native to North and Central America, but with some European, Asian, Australian, South American, and African species as well. Then they used global climate models to determine how the local climate of each species is expected to change by the end of this century.
Despite differences in local climate and in the vertebrates themselves, the results were consistent. The average rate of adaptation for 15 of the 17 groups was less than 1°C per million years. Two groups adapted slightly faster, but still below 2° per million years. So if a frog breeds in autumn because the temperature is right, it might adapt to warmer temperatures by breeding in December, January, or February. And lizards that survive on those eggs might have to change their diet. But the study found that such adaptations typically occur about 10,000 to 100,000 times too slowly to keep pace with global warming projections for the year 2100. The researchers reached the same conclusion for the expected regional increases and decreases in rainfall: Again, the species adapted 10,000 to 100,000 times too slowly.
Adapting too slowly does not mean certain death. A species can relocate. But due to habitat destruction and other factors, not all species can move. If a rodent lives on a mountain and warmer temperatures compel the animal to climb higher, it may run out of mountain while temperatures keep rising.
Wiens was surprised by the results because they suggest that the studied species, which typically adapt to less than 1°C of change per million years, now must adapt to 4° between now and the year 2100. "It's almost crazy to think that they're going to, in just a few decades, be more different than they've become over millions of years," he says.
Although isoniazid and rifampin, the two front-line TB drugs, came into use in 1952 and 1967 respectively, new TB infections still occur at the rate of roughly one per second. At any moment about a third of the existing human population is infected, mostly with inactive, latent TB, although active TB still kills over one million people each year. Russia, Africa, China and Southeast Asia have been especially hard hit by the epidemic.
Increased urbanization, public health complacency and immunity-weakening HIV have been major enablers of TB’s spread in recent decades. But the bacterium that causes TB (Mycobacterium tuberculosis - Mtb) also happens to be unusually well adapted for persisting in humans. Among other strategies, it frequently reverts to a dormant, non-replicating state and also creates attack-resistant cell colonies called biofilms, which contain a high proportion of non-replicating TB.
Compared to ordinary, fast-replicating TB, these other forms of TB are much less susceptible to existing drugs. Effective TB therapy thus requires months to years of regular dosing. But many patients quit before completing such long courses of treatment and end up incubating drug-resistant TB strains. Some strains are now “extensively drug-resistant” (XDR) and virtually untreatable?and usually fatal.
“The big challenge here has been to find a drug that clears TB infection more quickly, which means it has to be effective against both replicating and non-replicating TB,” said Wang, now also a scientist at the California Institute for Biomedical Research (CALIBR), a non-profit organization founded by Schultz for the early-stage development of new medicines.
Most existing TB drugs work poorly against non-replicating TB, having been developed principally for their ability to kill actively replicating TB. Wang therefore set up a different kind of screening test?one to detect compounds that block TB’s persistence-related ability to form biofilms.
Because experiments with live TB require a special (level 3) biosafety facility, Wang used a related but non-disease-causing mycobacterium for his initial, high-throughput test. Screening a diverse library of 70,000 compounds, he quickly found one, dubbed TCA1, that stood out for its ability to inhibit mycobacterial biofilms.
Tests in Jacobs’s biosafety level 3-certified laboratory confirmed that TCA1 also has powerful activity against TB. “Surprisingly, it turned out to kill both non-replicating and replicating TB,” Wang said.
In cell culture tests, TCA1 on its own killed more than 99.9% of ordinary, actively replicating TB bacteria within three weeks, and in combination with isoniazid or rifampin, could kill 100% within that period. TCA1 also showed strong effectiveness against drug-resistant TB strains, removing all signs of one common strain within a week when combined with isoniazid. Against a highly fatal “super-bug” strain from South Africa, which resists all conventional TB drugs, the new compound on its own had a kill rate of more than 99.999% within three weeks.
As expected, TCA1 also showed potent effects against non-replicating TB. Tests in mice confirmed TCA1′s effectiveness and suggested that the combination of TCA1 and isoniazid could be more powerful than existing drug regimens. TCA1 showed no sign of toxicity or adverse side effects in cell culture and mouse experiments, and also showed almost no tendency to induce drug resistance in TB.
The researchers found it works in an apparently unique way, largely by targeting two Mtb enzymes, one supporting TB replication and the other TB dormancy and persistence. “I don’t know of any other antibiotic that kills replicating bacteria through one pathway and non replicating bacteria through another, as this one does,” Wang said.
Several mechanisms that increase the rate of mutagenesis across the entire genome have been identified; however, how the rate of evolution might be promoted in individual genes is unclear. Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand.
A new study now describes the ubiquitous (core) genes in Bacillus subtilis and determine that 17% of them are on the lagging strand. The scientists find a higher rate of point mutations in the core genes on the lagging strand compared with those on the leading strand, with this difference being primarily in the amino-acid-changing (nonsynonymous) mutations. They determine that, overall, the genes under strong negative selection against amino-acid-changing mutations tend to be on the leading strand, co-oriented with replication. In contrast, on the basis of the rate of convergent mutations, genes under positive selection for amino-acid-changing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in many genes in the head-on orientation. Increased gene length and gene expression amounts are positively correlated with the rate of accumulation of nonsynonymous mutations in the head-on genes, suggesting that the conflict between replication and transcription could be a driving force behind these mutations. Indeed, using reversion assays, the scientists show that the difference in the rate of mutagenesis of genes in the two orientations is transcription dependent. Altogether, their findings indicate that head-on replication–transcription conflicts are more mutagenic than co-directional conflicts and that these encounters can significantly increase adaptive structural variation in the coded proteins. The researchers propose that bacteria, and potentially other organisms, promote faster evolution of specific genes through orientation-dependent encounters between DNA replication and transcription.
Water found in a deep, isolated reservoir in Timmins, Ont., has been trapped there for 1.5 billion to 2.64 billion years — since around the time the first multicellular life arose on the planet — Canadian and British scientists say.
The water pouring out of boreholes 2.4 kilometres below the surface in the northern Ontario copper and zinc mine is older than any other free-flowing water ever discovered. It is rich in dissolved gases such as hydrogen and methane that could theoretically provide support for microbial life.
"What we can be sure of is that we have identified a way in which planets can create and preserve an environment friendly to microbial life for billions of years," said a statement from Greg Holland, the Lancaster University geochemist who is the lead author of the study.
His Canadian co-authors included Barbara Sherwood Lollar and Georges Lacrampe-Couloume at the University of Toronto; Greg Slater at McMaster University in Hamilton; and Long Li, who is currently an assistant professor at the University of Alberta, but worked on the project while at the University of Toronto.
Some Canadian members of the team are currently testing the water to see if it contains microbial life — if they exist, those microbes may have been isolated from the sun and the Earth's surface for billions of years and may reveal how microbes evolve in isolation.
Microbes that have been isolated for tens of millions of years have been found in water with similar chemistry at even slightly deeper depths below the surface in a South African gold mine, using hydrogen gas as an energy source, the researchers noted.
The researchers estimated how old the water was based on an analysis of the xenon gas dissolved in it. Like many other elements, xenon comes in forms with different masses, known as isotopes. The water in the Timmins mine contained an unusually high level of lighter isotopes of xenon that are thought to have come from the Earth's atmosphere at the time it became trapped.
Medical researchers think specially tailored RNA sequences could turn off genes in patients’ cells to encourage wound healing or to kill tumor cells. Now researchers have developed a nanocoating for bandages that could deliver these fragile gene-silencing RNAs right where they’re needed (ACS Nano 2013, DOI:10.1021/nn401011n). The team hopes to produce a bandage that shuts down genes standing in the way of healing in chronic wounds.
Small interfering RNAs, or siRNAs, derail expression of specific genes in cells by binding to other RNA molecules that contain the code for those genes. Biologists have developed siRNAs that target disease-related genes. But for these siRNAs to reach the clinic, researchers must find a way to deliver the molecules safely to the right cells. Unfortunately, free oligonucleotides like siRNAs don’t fare well inside the body or cells as enzymes and acids quickly chop them up, says Paula T. Hammond, a chemical engineer at Massachusetts Institute of Technology.
Other groups have tackled this delivery challenge by attaching siRNAs to chemical carriers that protect the oligonucleotides as they travel through the bloodstream. The pharmaceutical company Sanofi-Aventis asked Hammond to design a vehicle that would work at the site of a wound or tumor, releasing the siRNAs over a long period of time. The company hoped that putting the biomolecules right where they’re needed, without them having to survive a trip through the bloodstream, would increase the efficacy of the treatment.
Hammond and her colleagues produced an siRNA-containing nanocoating that could be applied to a wide range of medical materials, such as bandages or biodegradable polymers doctors could implant during surgery to prevent an excised tumor from coming back. As the coating slowly dissolves, it releases siRNA molecules tethered to protective nanoparticles.
The thin films consist of two different materials: a peptide called protamine sulfate and calcium phosphate nanoparticles decorated with the therapeutic siRNAs. Other researchers have shown that similar nanoparticles help the nucleotides evade destruction once they’re taken up by cells (J. Controlled Release 2010, DOI: 10.1016/j.jconrel.2009.11.008).
The team alternately dips whatever they want to coat in water solutions of the two materials. The RNA and nanoparticles are negatively charged, and the peptides are positively charged. The two substances cling together due to electrostatic force, producing a film when the water dries.
To test their delivery method, the researchers coated woven nylon bandages with 80-nm-thick films and applied the bandages to layers of human and animal cells in culture. In one experiment, a bandage loaded with 19 µg of siRNA per square centimeter released two-thirds of its load over 10 days. Other bandages made using siRNAs targeting the gene for fluorescent green protein almost completely shut down the protein’s production in cells expressing the gene. Hammond says the group is now testing bandages that knock down MMP9, a collagen-destroying protein associated with slow healing in chronic wounds.
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