#The genomics of the sniffles: Nature News Genome sequences of the cold virus could reveal new secrets behind its prowess.
Heidi Ledford Rhinvirus capsid A human rhinovirus capsidj-Y Sgro/UW Madison Bang in the middle of sniffle season, researchers have released the full genome sequences of more than 100 strains of the viruses
responsible for most common colds. The viruses all belong to the rhinovirus family, and have RNA genomes. Their sequences, published this week in Science1,
could be used to design new therapies against colds or to determine, for example, why one strain can cause more severe symptoms than another."
"This is what rhinovirus researchers have been waiting for, "says virologist Carita Savolainen-Kopra of the National Institute for Health and Welfare in Helsinki, Finland.
colds in children can cause middle-ear infections or increase the likelihood of developing asthma.
Asthma sufferers, in turn, can find that catching a cold worsens their symptoms.""From that perspective, rhinovirus deserves to be attacked with the modern tools we have available to us,
"says Stephen Liggett, director of cardiopulmonary genomics at the University of Maryland Medical center in Baltimore,
What's more, a newly discovered class of rhinoviruses called HRV-C can cause serious, flu-like lung infections."
"says study author Ann Palmenberg, a virologist at the University of Wisconsin, Madison.""These viruses are really nasty.
"Sniffle-omics All this havoc is caused by a tiny virus only about 30 nanometres in diameter, with a genome that is a mere 7,
000 bases long a minute speck compared with the human genome, which has more than three billion bases.
Although the genomes of a few strains of cold virus had been sequenced, no one had compiled the full sequences of the 99 strains frequently studied by researchers.
Rhinovirus genome tree The human rhinovirus genome tree (click for larger image. Science Liggett, Palmenberg and their colleagues decided to fill this gap by sequencing the reference-library strains,
along with 10 additional viruses isolated from patients with upper respiratory infections. They compared these sequences
and the previously reported HRV-C genomes with one another to look for patterns and evolutionary relationships (see human rhinovirus genome tree, right).
The results suggest that three of the strains may comprise a further new rhinovirus species. The sequences also indicate that
the viruses may exchange portions of their genomes a phenomenon that, until now, had not been described in rhinoviruses.
In addition, all of the strains have extremely variable RNA sequences in one specific region of the genome.
Palmenberg also believes that the genome is structured to allow ribosomes the molecular machines that read RNA and produce a protein,
to rapidly skip over regions of the genome that do not code for proteins. The mechanism may make the viruses more competitive by allowing them to synthesize their proteins more quickly,
The data may also reveal the viral characteristics that are associated with longer more symptomatic infections."
"To date, there has been a lack of understanding as to which rhinovirus gives you a more complex cold,
says Caroline Tapparel, a virologist at the University Hospital of Geneva in Switzerland, but she cautions that with the exception of the troublesome HRV-C viruses,
variable viral genome sequences may not prove to be the primary determinant of virulence.""Ultimately, the immune status of the patient may have a greater impact,
and leukaemia after receiving a stem-cell transplant from a donor who is genetically resistant to HIV.
and prepared to perform a transplant. But haematologist Gero H tter of the Charit Universit tsmedizin in Berlin took the search for a donor one step further.
but when he realized that his patient would need a transplant, he remembered a paper he had read more than a decade earlier about HIV resistance in people who carry a specific genetic mutation.
The mutation is a short deletion in the CCR5 gene. The gene encodes a receptor that HIV uses to enter immune cells called CD4+T cells.
About 1%of the European population carries the CCR5 mutation in both copies of the CCR5 gene,
making such people much less likely to contract the virus . If H tter could replace his patient's immune cells with cells that lacked the CCR5 receptor,
his patient might be less susceptible to HIV infection. The patient had 80 matches in the bone-marrow registries of the German Bone marrow Donor Center,
and H tter reasoned that one of those matches might also carry CCR5 mutations. Donor number 61 turned out to be the one,
and in February 2007, the transplant was performed. Even though the technique has only been applied in one patient
the results are valuable, says James Riley, an HIV researcher at the University of Pennsylvania in Philadelphia.
Of all the'n=1'experiments out there, this is a good one, he says. It's a tremendous proof of principle that
if you can make the majority of your cells resistant to infection, you can really stop the virus. Meanwhile,
H tter says that a different team of physicians intends to perform the same procedure in another HIV-positive patient with leukaemia.
The virus could be lurking in cells that doctors have not been able to test such as cells in the brain or heart.
In addition, there is another strain of HIV that does not use CCR5 receptors to invade cells.
The risks involved with a bone-marrow transplant far outweigh those that come with years of antiretroviral drug therapy
Before receiving the transplant, recipients are conditioned with drugs and radiation to destroy their own blood-producing stem cells.
The procedure leaves them vulnerable to infection, and there is also the possibility that their bodies will eventually reject the transplant.
You could. One CCR5 inhibitor, called maraviroc, is made by the pharmaceutical company Pfizer and is approved for use in the United states and Europe.
Other companies are busy developing additional CCR5-targeting drugs. Unfortunately, maraviroc does not completely prevent the virus from binding to CCR5,
and it can only be used in combination with other antiretrovirals. Basically HIV can find its way around the drug and still use CCR5
says Riley, who adds that the virus might outcompete the inhibitor, or may be able to bind to a different region of CCR5 than the drug.
Others are trying gene therapy approaches to prevent CCR5 from being made at all. For example, Riley has been collaborating with Sangamo Biosciences,
a biotechnology company based in Richmond, California, to determine whether the company's technique for snipping out targeted genes could be used to delete the CCR5 gene.
Sangamo announced last week that it has launched a Phase I clinical trial that will involve removing a sample of the participant's T cells,
deleting the CCR5 gene, and then infusing the cells back into the patient. The trial is a first step towards ascertaining the safety of the technique not its efficacy
and participants will not be conditioned to destroy their unmodified T cells s
#What causes schizophrenia?:Nature News Findings from a'brain training'study challenge theory. Researchers in Sweden have revealed a surprising change in brain biochemistry that occurs during the training of working memory,
a buffer that stores information for the few second required to solve problems or even to understand what we are reading.
The discovery may have implications for understanding disorders in which working memory is deficient such as schizophrenia and attention deficit hyperactivity disorder (ADHD.
Working memory depends on the transmission of signals in certain parts of the brain by the chemical dopamine and one of its receptors, the D1 receptor, particularly in the parietal and frontal regions of the cortex.
The efficiency of working memory drops off as people age. But the'use-it-or-lose it'adage holds true working memory can be improved through training.
Torkel Klingberg, a neurologist at the Karolinska Institute in Stockholm, and his colleagues studied what happened to D1 receptors in the brains of healthy young men during such training1.
In particular, the researchers wanted to see whether the density of the receptors changes because when dopamine is plentiful,
dopamine receptors'downregulate'that is, move from the nerve-cell membrane to the inside of the cell,
where they cannot be activated. This is a normal'tune-down'mechanism to avoid overstimulation. Brain training Klingberg's team organized a five-week training programme for 13 volunteers aged between 20 and 28.
Every day, they spent around half an hour in total on five computer-based tests designed to stretch their working memories.
reporting results by clicking on relevant numbers in a grid on the screen. Using brain imaging techniques, the scientists measured levels and locations of dopamine receptors in brain areas of interest in each participant before and after training.
They found that the density of D1 receptors in the parietal and frontal cortices fell as working memory improved."
"The density of neurotransmitter receptors is known to change in psychiatric disorders like schizophrenia, and this has been considered a cause of the diseases,
"says Klingberg.""But now we see that cognitive activity also affects receptor density.""In the future, researchers will need to consider
or part of the disease process itself, he says. Calming effect?""This is an important consideration that applies to many findings of purported brain changes in mental disease,"comments Sol Snyder, a neuroscientist at Johns hopkins university in Baltimore, Maryland."
"Many findings of altered brain biochemistry may simply reflect the patients'inattentiveness, he says. Klingberg says that his team's results may also have practical implications for training working memory.
Children diagnosed with ADHD are treated frequently with drugs such as Ritalin that affect the dopamine system.
In some centres, children undergo working-memory training programmes.""We are interested now to see if a combination of cognitive training and pharmacological intervention could be more effective than either alone,
"he says h
#Neanderthal genome to be unveiled: Nature News The entire genome of a 38,000-year-old Neanderthal has been sequenced by a team of scientists in Germany.
The group is already extracting DNA from other ancient Neanderthal bones and hopes that the genomes will allow an unprecedented comparison between modern humans and their closest evolutionary relative.
The three-year project, which cost about#5 million (US$6. 4 million), was carried out at the Max Planck Institute for Evolutionary Anthropology in Leipzig.
Project leader Svante Pääbo will announce the results of the preliminary genomic analysis at the American Association for the Advancement of Science annual meeting in Chicago
computational biologist Richard Green, is coordinating the analysis of the genome's 3 billion base pairs.
Comparisons with the human genome may uncover evidence of interbreeding between Neanderthals and humans, the genomes
The genome may also deliver more details about how these species developed their different physical traits,
adapted to their environment and evolved to fight disease. Despite previous reports that the German group's Neanderthal samples may have been contaminated with DNA from modern humans1,
an analysis of a Neanderthal mitochondrial genome2 has allowed the researchers to largely rule out such contamination."
"says Edward Rubin, director of the US Joint Genome Institute in Walnut creek, California, which is also sequencing Neanderthal DNA
Almost all of the Neanderthal genome to be unveiled in Chicago comes from DNA extracted from a single bone originally discovered in a cave near Vindija in Croatia.
and so is well on the way to creating a library of Neanderthal genomes that would allow stronger comparisons with modern humans.
Pääbo says that his group will publish a first draft of the entire Neanderthal genome later this year,
However, some published human genomes had all their base pairs read eight to ten times before publication.
The team says that its single-read of the Neanderthal genome is sufficient for publication
because the technique used does not rely on the same DNA reassembly process used in conventional'shotgun'sequencing g
#Tighter nanotech regulations touted: Nature News The Canadian government is about to introduce the first mandatory programme in the world for reporting the safety of manufactured nanomaterials.
The scheme will require companies to provide any details that they have about the physical,
chemical and toxicological properties of nanomaterials they make or import in quantities greater than one kilogram.
The government agencies Environment Canada and Health Canada will use the data to make risk assessments for the materials
In 2007, the government asked the Council of Canadian Academies to assess the state of health and safety in nanotechnology.
The council's panel of experts chaired by physicist Pekka Sinervo from the University of Toronto in Ontario,
reported in July 2008 that very little information existed about the risks associated with nanomaterials."
"There is an urgency to come to grips with this issue, "says Sinervo. But he cautions that the success of the scheme will rely on how well the Canadian approach integrates with its main trading partners in other nations.
Voluntary data-reporting schemes have been trialled in other countries with limited success. The ongoing voluntary programme of the US Environmental protection agency (EPA) has received so far submissions from 29 companies on more than 120 nanoscale materials;
"says Colin Finan, from the Project on Emerging Nanotechnologies, based at the Woodrow wilson International Center for Scholars in WASHINGTON DC.
The UK Department for Environment, Food and Rural affairs (DEFRA) ran a two-year voluntary reporting programme from September 2006,
Authorisation and Restriction of Chemical substances) regulations are currently being reviewed to clarify how nanomaterials are dealt with.
Anne Mitchell, executive director of the Canadian Institute for Environmental law and Policy in Toronto expects a mandatory scheme to work more effectively than voluntary programmes,
and is pleased that companies are expected to provide their data within four months of beginning to use
or supply a nanomaterial. Finan expects the United states, and perhaps other countries, to follow Canada's lead."
"says Steve Morgan, nanotechnologies policy adviser at DEFRA.""We're all watching with interest
#Rising air pollution clouds climate debate: Nature News Air pollution that is harmful to human health has increased over all populated continents except Europe since 1973, according to an extensive survey.
The results play into a longstanding debate over whether the Earth's skies are dimming
or brightening, how this affects the amount of sunlight reaching the planet's surface and what that means for climate change.
Two studies published in Science in 2005 concluded that a global dimming trend that began in the 1950s has been replaced since 1990 by global brightening1,
2. The likely effect of all that extra solar radiation reaching the Earth's surface would be faster global warming.
Now a study published in Science concludes that in fact skies became dimmer over most land areas between 1973 and 20073.
Kaicun Wang, an atmospheric scientist at the University of Maryland in College Park, and his colleagues based their conclusions on visibility measurements, a good proxy for aerosol pollution, from 3, 250 meteorological stations around the world.
They found that visibility has tended to decrease over that period, the most pronounced dimming having occurred in South Asia and South america.
now that air pollution is a serious health risk, "says Wang.""But attempts, such as China's, to regulate air quality have not yet borne fruit."
"Significant questions remain about what these results means for climate change, because soot and different kinds of aerosols can affect cloud formation in very different ways.
meaning that the net effect of aerosol pollution on global temperatures is worryingly uncertain. Another complication is that soot from burning biofuels,
"The issue of global dimming versus global brightening is not just a question of aerosols, "agrees Martin Wild, an atmospheric scientist at The swiss Federal Institute of technology in Zurich,
and previously in North america if coal is replaced by oil and natural gas as an energy source, and if particulate filters in cars and factories become more common o
#Obama appoints first federal IT chief: Nature News The Blackberry-toting Barack Obama last week took a step towards modernizing the US government's information system by appointing Vivek Kundra to the newly created post of chief information officer.
Kundra, who for the past two years was chief technology officer (CTO) for WASHINGTON DC, will have authority over IT spending across the entire federal government,
"says Andrew Rasiej, founder of Personal Democracy Forum, an annual conference and website on politics and technology.
which include getting city agencies to provide public data in standard formats such as XML and RSS feeds.
Kundra also embraced'cloud computing'by moving all 38,000 employees for WASHINGTON DC onto the Google Apps office suite
which stores data and applications online rather than on individual computers. And he recently implemented an internal management tool in
and author of the blog CTOVISION. com."And Vivek has racked them up.""""There are three pillars to my agenda,
"We want to launch a data. gov site to make a vast array of government data public."
Likewise, any data streams coming out of data. gov will have to comply with legislation that protects citizens'privacy y
#Diamond defects shrink MRI to the nanoscale Diamond-based quantum devices can now make nuclear magnetic resonance measurements on the molecular scale.
Work by two independent groups will make it easier to find out the structure of single biological molecules such as proteins without destroying
Nuclear magnetic resonance (NMR) and its close cousin magnetic resonance imaging (MRI) give information about a sample s structure by detecting the weak magnetic forces in certain atomic nuclei, such as hydrogen.
and MRI to the molecular level, says Friedemann Reinhard, a physicist at the University of Stuttgart in Germany.
His team is one of two that have used NMR to detect hydrogen atoms in samples measuring just a few nanometres across1.
The second team2 was led by Daniel Rugar, manager of nanoscale studies at IBM s Almaden Research center in San jose, California.
Probing single molecules a few nanometres wide has been a major frustration in NMR. The detectors need to be a similar size to the sample
and the magnetic coils usually used cannot easily be made smaller than a few micrometres. NMR and MRI measurements on the nanoscale have been done using powerful nanomagnets in a technique called magnetic resonance force microscopy
#but that only worked with very cold samples. Rugar and Reinhard took a different approach.
Both teams made diamonds with defects in their crystal structure#a single nitrogen atom next to a missing carbon atom, a few nanometres below the surface.
This gives the diamond a red fluorescent glow, which can be bright or dull depending on
Reinhard s team placed different kinds of samples onto their diamond and watched how the nuclear resonance in them influenced the spinning electrons in the nitrogen.
The researchers worked out that most of the signal came from a volume just 5 nanometres across inside the sample.
Rugar s team did a similar experiment with an organic polymer, and probed a volume of about the same size.
The idea would be to place a diamond crystal onto the tip of a scanning microscope,
Diamond nanocrystals immersed in a cell's cytoplasm could essentially produce real-time films of the activity of single molecules,
such as a protein folding, writes Philip Hemmer, a solid-state physicist at Texas A&m University in College Station."
#RNA fragments may yield rapid, accurate cancer diagnosis An article by Scientific American. Fragments of RNA that cells eject in fatty droplets may point the way to a new era of cancer diagnosis,
potentially eliminating the need for invasive tests in certain cases. Cancer tumor cells shed microvesicles containing proteins and RNA fragments, called exosomes, into cerebral spinal fluid, blood, and urine.
Within these exosomes is genetic information that can be analyzed to determine the cancer s molecular composition and state of progression.
Researchers at Massachusetts General Hospital discovered that exosomes preserve the genetic information of their parent cells in 2008
however exosomes have not seen widespread clinical testing as a means of cancer diagnosis until now.""We have never really been able to detect the genetic components of a tumor by blood
or spinal fluid, says Harvard university neurologist Fred Hochberg.""This is really a new strategy. He says exosome diagnostic tests could potentially detect
and monitor the progression of a wide variety of cancers. He is one of the lead researchers in a multicenter clinical study using new exosomal diagnostic tests developed by New york city-based Exosome Diagnostics to identify a genetic mutation found exclusively in glioma, the most common form of brain cancer.
When treating other forms of cancer, surgeons are able to biopsy tumors to diagnose and monitor the state of the disease.
For brain cancers like glioma, however, multiple biopsies can be life threatening. Bob Carter head of neurosurgery at the University of California, San diego, says well-preserved RNA in blood
and spinal fluid enables researchers to test and monitor for these genetic changes noninvasively. He says study researchers separate exosomes from bio-fluids with a diagnostic kit
and then extract the relevant genomic information. Once the specific cancer mutation is identified, clinicians will periodically draw additional bio-fluids to monitor the mutation levels to determine
whether a patient is responding to therapy. Whereas Magnetic resonance imaging (MRI) is a useful tool, tumors only show up on imaging scans once they are at least one millimeter in diameter
and comprise about 100, 000 tumor cells. By that time, it may be too late for an early intervention.
On the flip side, MRIS can also yield false positives. Hochberg says individuals who have been treated with conventional radiation therapy often have benign residual tissue from dying tumor cells that have been killed by the treatment but
which the body has eliminated not yet. This tissue is mistaken often for tumor growth on a MRI scan."
"You would identify to the patient that the drug is not working when in reality it is doing well,
Hochberg says.""On the other hand, having an easily accessible biomarker for glioma would give you a clear response.
There are 18 U s. hospitals participating in the clinical trial, sponsored by the Accelerated Brain Cancer Cure Foundation.
Hochberg says study researchers have recruited 41 of 120 patients so far. Preliminary results will be presented in April at the International Society for Extracellular Vesicles Symposium in Boston.
From a technical standpoint I don t believe there is a barrier, Carter says.""This test can certainly be used now,
what we are trying to finalize is the sensitivity and specificity of the test. Exosomes may be a reliable method of screening for prostate cancer as well.
A PSA test is currently the most common, noninvasive means to screen for prostate cancer in the U s. PSA testing measures for elevated levels of prostate specific-antigen antigen,
a protein produced by the prostate gland that is used to liquefy semen in men. The higher a man s PSA level, the more likely it is that he has prostate cancer,
says James Mckiernan, director of urologic oncology at Columbia University Medical center. There are additional reasons, however, for high PSA levels
-and some men with prostate cancer do not always have elevated PSA, he added. In addition, for many cases of prostate cancer, new research published in May 2012 in The New england Journal of Medicine shows that treatment does not actually extend the life of the patient."
"Honestly PSA is not cancer-specific, says Sudhir Srivastava, head of the National Cancer Institute s Cancer Biomarkers Research Group."
"Exosomes could be very much more cancer specific. PSA might give you one specific biomarker for cancer identification,
but exosomes can give you an entire disease specific profile so you would know whether or not it is a form of prostate cancer that necessitates treatment.
Researchers at Exosome have developed a diagnostic kit for prostate cancer with a diagnostic accuracy of around 75 percent-a rate comparable with that of actually taking a tissue biopsy,
says Wayne Comper, a renal physiologist and chief science officer at Exosome. He says the first diagnostic kit could be available commercially by the end of 2013.
Researchers use the kit to look for the genetic biomarker TMPRSS2: ERG or T: E in exosomes taken from a urine sample.
Comper says levels of T: E are nine times higher in a cancerous prostate versus a healthy one.
Mckiernan says researchers found these exosomal diagnostic tests gave better predictive results for cancer than current prescreening methods, such as PSA.
PSA levels are measured via a blood draw but also require a visit to a doctor s office for a digital rectal exam,
something that isn t necessary with an exosomal diagnostic test.""Our study got enough interest to put together a series of sites for investigation to lead to potential FDA approval of this particular kit,
he says.""That is ongoing right now and the last time I checked there were about 1, 000 patients who have been enrolled in the study.
More from Scientific American. Srivastava says Exosome's prostate kit could prove to be extremely relevant in cancer treatment
if it survives the U s. Food and Drug Administration s grueling approval process. He says it is a precursor to
what he hopes will be a series of multiple-gene-signature cancer tests.""We are looking for something with about 90 percent accuracy before it can be used by itself for clinical diagnosis,
he says.""NCI has done two prostate trials with exosomes to date and is looking into creating standard isolation procedures to make the tests more specific.
In the meantime Srivastava says exosomal tests could be used in conjunction with current methods of diagnosis like PSA to help physicians better determine
if the nature of a prostate tumor is severe enough to warrant radical treatment or removal without ever performing a biopsy."
"If someone has high PSA and also has biomarkers which are positive in exosomes that would be a great test,
he says.""Exosomes have the potential to really further the detection of cancer and help analyze things that would have otherwise not been detected noninvasively y
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