By Jeremy Laurance, Health Editor
Wednesday, 30 January 2008
Scientists performing experimental brain surgery on a man aged 50 have stumbled across a mechanism that could unlock how memory works.
The accidental breakthrough came during an experiment originally intended to suppress the obese man's appetite, using the increasingly successful technique of deep-brain stimulation. Electrodes were pushed into the man's brain and stimulated with an electric current. Instead of losing appetite, the patient instead had an intense experience of déjà vu. He recalled, in intricate detail, a scene from 30 years earlier. More tests showed his ability to learn was dramatically improved when the current was switched on and his brain stimulated.
Scientists are now applying the technique in the first trial of the treatment in patients with Alzheimer's disease. If successful, it could offer hope to sufferers from the degenerative condition, which affects 450,000 people in Britain alone, by providing a "pacemaker" for the brain.
Three patients have been treated and initial results are promising, according to Andres Lozano, a professor of neurosurgery at the Toronto Western Hospital, Ontario, who is leading the research.
more....
Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification
Emerging and re-emerging infectious diseases, especially those caused by drug-resistant bacteria, are a major problem worldwide. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) appeared rapidly and unexpectedly in the United States, resulting in an epidemic caused primarily by isolates classified as USA300. The evolutionary and molecular underpinnings of this epidemic are poorly understood. Specifically, it is unclear whether there has been clonal emergence of USA300 isolates or evolutionary convergence toward a hypervirulent phenotype resulting in the independent appearance of similar organisms. To definitively resolve this issue and understand the phylogeny of USA300 isolates, we used comparative whole-genome sequencing to analyze 10 USA300 patient isolates from eight states in diverse geographic regions of the United States and multiple types of human infection. Eight of 10 isolates analyzed had very few single nucleotide polymorphisms (SNPs) and thus were closely related, indicating recent diversification rather than convergence. Unexpectedly, 2 of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate (P = 0.0002), providing strong support to the idea that minimal genetic change in the bacterial genome can have profound effects on virulence. Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300. The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant S. aureus (known as phage-type 80/81 S. aureus) in the 1950s.
Adam D. Kennedy*, Michael Otto*, Kevin R. Braughton*, Adeline R. Whitney*, Liang Chen, Barun Mathema, Jose R. Mediavilla, Kelly A. Byrne*, Larye D. Parkins*, Fred C. Tenover, Barry N. Kreiswirth, James M. Musser, and Frank R. DeLeo*,¶
*Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; International Center for Public Health, Public Health Research Institute, 225 Warren Street, Newark, NJ 07103; Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30333; and Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute and Department of Pathology, 6565 Fannin Street, B490, Houston, TX 77030
Edited by Richard M. Krause, National Institutes of Health, Bethesda, MD, and approved December 10, 2007 (received for review October 26, 2007)
Adam D. Kennedy*, Michael Otto*, Kevin R. Braughton*, Adeline R. Whitney*, Liang Chen, Barun Mathema, Jose R. Mediavilla, Kelly A. Byrne*, Larye D. Parkins*, Fred C. Tenover, Barry N. Kreiswirth, James M. Musser, and Frank R. DeLeo*,¶
*Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; International Center for Public Health, Public Health Research Institute, 225 Warren Street, Newark, NJ 07103; Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30333; and Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute and Department of Pathology, 6565 Fannin Street, B490, Houston, TX 77030
Edited by Richard M. Krause, National Institutes of Health, Bethesda, MD, and approved December 10, 2007 (received for review October 26, 2007)
Enhanced hydrogen production from glucose by metabolically engineered Escherichia coli.
To utilize fermentative bacteria for producing the alternative fuel hydrogen, we performed successive rounds of P1 transduction from the Keio Escherichia coli K-12 library to introduce multiple, stable mutations into a single bacterium to direct the metabolic flux toward hydrogen production. E. coli cells convert glucose to various organic acids (such as succinate, pyruvate, lactate, formate, and acetate) to synthesize energy and hydrogen from formate by the formate hydrogen-lyase (FHL) system that consists of hydrogenase 3 and formate dehydrogenase-H. We altered the regulation of FHL by inactivating the repressor encoded by hycA and by overexpressing the activator encoded by fhlA, removed hydrogen uptake activity by deleting hyaB (hydrogenase 1) and hybC (hydrogenase 2), redirected glucose metabolism to formate by using the fdnG, fdoG, narG, focA, focB, poxB, and aceE mutations, and inactivated the succinate and lactate synthesis pathways by deleting frdC and ldhA, respectively. The best of the metabolically engineered strains, BW25113 hyaB hybC hycA fdoG frdC ldhA aceE, increased hydrogen production 4.6-fold from glucose and increased the hydrogen yield twofold from 0.65 to 1.3 mol H(2)/mol glucose (maximum, 2 mol H(2)/mol glucose).
Maeda T, Sanchez-Torres V, Wood TK.
Artie McFerrin Department of Chemical Engineering, Texas A & M University, 220 Jack E. Brown Building, College Station, TX, 77843-3122, USA.
Maeda T, Sanchez-Torres V, Wood TK.
Artie McFerrin Department of Chemical Engineering, Texas A & M University, 220 Jack E. Brown Building, College Station, TX, 77843-3122, USA.
Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes
To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require 70 min to deliver 650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered "hybrid" mechanism of DNA electromigration, in which DNA molecules alternate rapidly between reptating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs.
Christopher P. Fredlake*, Daniel G. Hert*, Cheuk-Wai Kan*, Thomas N. Chiesl*, Brian E. Root, Ryan E. Forster, and Annelise E. Barron*,,
Departments of *Chemical and Biological Engineering, Chemistry, and Materials Science and Engineering, Northwestern University, Evanston, IL 60208
Christopher P. Fredlake*, Daniel G. Hert*, Cheuk-Wai Kan*, Thomas N. Chiesl*, Brian E. Root, Ryan E. Forster, and Annelise E. Barron*,,
Departments of *Chemical and Biological Engineering, Chemistry, and Materials Science and Engineering, Northwestern University, Evanston, IL 60208
New Mode of Cell Communication Discovered
By Steve Mitchell
ScienceNOW Daily News
9 January 2008
Like teenagers, cells in our bodies constantly chatter back and forth. But instead of zapping text messages, they relay signals with molecules. Now, researchers have discovered a surprisingly tiny new messenger in worms: protons. The find raises the possibility that the subatomic particle plays the same role in humans, the researchers say.
Research in mice has hinted that protons--hydrogen atoms stripped of their electrons--might act as messengers, but until now direct evidence has been lacking. A team led by biologist Erik Jorgensen of the University of Utah, Salt Lake City, made the discovery while investigating how the worm Caenorhabditis elegans contracts certain muscles around its intestines to squeeze out waste. Previous experiments had ruled out several neurotransmitters known to aid defecation, suggesting that a novel molecule might be playing a role.
After sequencing the DNA of worms with defects in muscle contraction, the team identified mutations in a gene called PBO4. This gene encodes a protein located on the outer surface of intestinal cells, where it brings sodium ions into the cell while pumping protons out. This hinted that protons might play a role in making the muscles contract.
more....http://sciencenow.sciencemag.org
ScienceNOW Daily News
9 January 2008
Like teenagers, cells in our bodies constantly chatter back and forth. But instead of zapping text messages, they relay signals with molecules. Now, researchers have discovered a surprisingly tiny new messenger in worms: protons. The find raises the possibility that the subatomic particle plays the same role in humans, the researchers say.
Research in mice has hinted that protons--hydrogen atoms stripped of their electrons--might act as messengers, but until now direct evidence has been lacking. A team led by biologist Erik Jorgensen of the University of Utah, Salt Lake City, made the discovery while investigating how the worm Caenorhabditis elegans contracts certain muscles around its intestines to squeeze out waste. Previous experiments had ruled out several neurotransmitters known to aid defecation, suggesting that a novel molecule might be playing a role.
After sequencing the DNA of worms with defects in muscle contraction, the team identified mutations in a gene called PBO4. This gene encodes a protein located on the outer surface of intestinal cells, where it brings sodium ions into the cell while pumping protons out. This hinted that protons might play a role in making the muscles contract.
more....http://sciencenow.sciencemag.org
Why We're Different: Probing the Gap Between Apes and Humans
Science 25 January 2008: Vol. 319. no. 5862, pp. 404 - 405
Michael Balter
We sometimes see apes and monkeys in the movies, but we never see them at the movies. Although nonhuman primates can do remarkable things--chimps have rudimentary cultures, and some monkeys have highly complex social systems--none shows the kind of creativity and innovation that are the hallmarks of Homo sapiens. Researchers have long puzzled about which human behaviors stem from our primate roots and which are unique to the hominid line.
Beginning in the 1960s, scientists focused on the similarities, as lab and field studies revealed that the cognitive talents of other primates had been underestimated. But during the past decade or so, researchers say, there has been renewed interest in the traits that set us apart. At a recent meeting* here, anthropologist Carel van Schaik of the University of Zurich, Switzerland, emphasized this evolutionary divergence. "Mind the gap!" he said in a keynote talk. "Humans have a huge number of [novel] characteristics." Indeed, participants at the meeting, which was designed to compare and contrast humans and nonhuman primates, demonstrated several of these seemingly unique human behaviors: advanced planning (the conference was months in the making), social organization and cooperation (everyone showed up at the same time and place), and culture and teaching through language.
At the conference, researchers heard evidence that many of these behaviors, such as planning, may have deep evolutionary roots. But some talents, such as cultural innovation, seem unique to our species, and others, including altruism, may represent a novel blend of old and new characteristics. The challenge now, says van Schaik, "is to figure out how one ape among many--humans--could become so radically different."
more....http://www.sciencemag.org
Michael Balter
We sometimes see apes and monkeys in the movies, but we never see them at the movies. Although nonhuman primates can do remarkable things--chimps have rudimentary cultures, and some monkeys have highly complex social systems--none shows the kind of creativity and innovation that are the hallmarks of Homo sapiens. Researchers have long puzzled about which human behaviors stem from our primate roots and which are unique to the hominid line.
Beginning in the 1960s, scientists focused on the similarities, as lab and field studies revealed that the cognitive talents of other primates had been underestimated. But during the past decade or so, researchers say, there has been renewed interest in the traits that set us apart. At a recent meeting* here, anthropologist Carel van Schaik of the University of Zurich, Switzerland, emphasized this evolutionary divergence. "Mind the gap!" he said in a keynote talk. "Humans have a huge number of [novel] characteristics." Indeed, participants at the meeting, which was designed to compare and contrast humans and nonhuman primates, demonstrated several of these seemingly unique human behaviors: advanced planning (the conference was months in the making), social organization and cooperation (everyone showed up at the same time and place), and culture and teaching through language.
At the conference, researchers heard evidence that many of these behaviors, such as planning, may have deep evolutionary roots. But some talents, such as cultural innovation, seem unique to our species, and others, including altruism, may represent a novel blend of old and new characteristics. The challenge now, says van Schaik, "is to figure out how one ape among many--humans--could become so radically different."
more....http://www.sciencemag.org
Biofuels on a Big Scale
By Robert F. Service
ScienceNOW Daily News
7 January 2008
On paper, making biofuels from switchgrass and other perennials that need not be replanted seems like a no-brainer. Use the sun's energy to grow the crop, and then convert it to liquid fuels to power our cars without the need for gasoline. But so far, experiments with these "cellulosic" crop-based fuels have only been conducted on small scales, leaving open the question of how feasible the strategy is. Now, the first large-scale study shows that switchgrass yields more than five times the energy needed to grow, harvest, and transport the grass and convert it to ethanol. The results could propel efforts to sow millions of hectares of marginal farmland with biofuel crops.
Previous studies on switchgrass plots suggested that ethanol made from the plant would yield anywhere from 343% to 700% of the energy put into growing the crop and processing it into biofuel. But these studies were based on lab-scale plots of about 5 square meters. So 6 years ago, Kenneth Vogel, a geneticist with the U.S. Department of Agriculture in Lincoln, Nebraska, and colleagues set out to enlist farmers for a much larger evaluation. Farmers planted switchgrass on 10 farms, each of which was between 3 and 9 hectares. They then tracked the inputs they used--diesel for farm equipment and transporting the harvested grasses, for example--as well as the amount of grass they raised over a 5-year period. After crunching the numbers, Vogel and his colleagues found that ethanol produced from switchgrass yields 540% of the energy used to grow, harvest, and process it into ethanol. Equally important, the researchers found that the switchgrass is carbon neutral, as it absorbs essentially the same amount of greenhouse gases while it's growing as it emits when burned as fuel.
more...http://sciencenow.sciencemag.org
ScienceNOW Daily News
7 January 2008
On paper, making biofuels from switchgrass and other perennials that need not be replanted seems like a no-brainer. Use the sun's energy to grow the crop, and then convert it to liquid fuels to power our cars without the need for gasoline. But so far, experiments with these "cellulosic" crop-based fuels have only been conducted on small scales, leaving open the question of how feasible the strategy is. Now, the first large-scale study shows that switchgrass yields more than five times the energy needed to grow, harvest, and transport the grass and convert it to ethanol. The results could propel efforts to sow millions of hectares of marginal farmland with biofuel crops.
Previous studies on switchgrass plots suggested that ethanol made from the plant would yield anywhere from 343% to 700% of the energy put into growing the crop and processing it into biofuel. But these studies were based on lab-scale plots of about 5 square meters. So 6 years ago, Kenneth Vogel, a geneticist with the U.S. Department of Agriculture in Lincoln, Nebraska, and colleagues set out to enlist farmers for a much larger evaluation. Farmers planted switchgrass on 10 farms, each of which was between 3 and 9 hectares. They then tracked the inputs they used--diesel for farm equipment and transporting the harvested grasses, for example--as well as the amount of grass they raised over a 5-year period. After crunching the numbers, Vogel and his colleagues found that ethanol produced from switchgrass yields 540% of the energy used to grow, harvest, and process it into ethanol. Equally important, the researchers found that the switchgrass is carbon neutral, as it absorbs essentially the same amount of greenhouse gases while it's growing as it emits when burned as fuel.
more...http://sciencenow.sciencemag.org
Another Big Bang for Biology
By Phil Berardelli
ScienceNOW Daily News
3 January 2008
Researchers have uncovered what they think is a sudden diversification of life at least 30 million years before the Cambrian period, the time when most of the major living groups of animals emerged. If confirmed, the find reinforces the idea that major evolutionary innovations occurred in bursts.
The main points of Charles Darwin's theory of evolution, which he carefully laid out in The Origin of Species 149 years ago, have stood the test of time. But where Darwin assumed that natural selection proceeds slowly and orderly--much the way Isaac Newton imagined a clockwork universe--modern investigations have shown that the process more resembles the chaotic world of quantum physics. Scores of new groups of species can appear within a few million years. By far the biggest and most famous of these events is the Cambrian explosion, a period between 542 million and 520 million years ago, when due to some still-unknown cause, the ancestors of nearly all extant groups, or phyla, of animals appeared.
more....www.sciencenow.sciencemag.org
ScienceNOW Daily News
3 January 2008
Researchers have uncovered what they think is a sudden diversification of life at least 30 million years before the Cambrian period, the time when most of the major living groups of animals emerged. If confirmed, the find reinforces the idea that major evolutionary innovations occurred in bursts.
The main points of Charles Darwin's theory of evolution, which he carefully laid out in The Origin of Species 149 years ago, have stood the test of time. But where Darwin assumed that natural selection proceeds slowly and orderly--much the way Isaac Newton imagined a clockwork universe--modern investigations have shown that the process more resembles the chaotic world of quantum physics. Scores of new groups of species can appear within a few million years. By far the biggest and most famous of these events is the Cambrian explosion, a period between 542 million and 520 million years ago, when due to some still-unknown cause, the ancestors of nearly all extant groups, or phyla, of animals appeared.
more....www.sciencenow.sciencemag.org
Scientists Synthesize a Genome From Scratch
By Elizabeth Pennisi
ScienceNOW Daily News
24 January 2008
Researchers have rebuilt an entire genome from scratch, they report online today in Science. Although the team has yet to demonstrate that this DNA can substitute for the real thing, the work paves the way for customized bacteria that could efficiently produce drugs, biofuels, and other molecules useful to humankind.
Ever since his group decoded the genome of Mycoplasma genitalium, a parasitic bacterium that lives in the human urogenital tract, sequencing maverick J. Craig Venter has wanted to remake the bug's genome in the lab. At just under 600,000 bases, M. genitalium sports the smallest known genome for a free-living organism, and Venter hoped that an artificial genome could be modified to turn the bacterium into a living chemical-manufacturing plant.
Last year, Venter and his colleagues developed a technique for replacing M. genitalium's genome with another natural genome from a different species (Science, 3 August 2007, p. 632). But synthesizing the M. genitalium genome from the ground up proved challenging, in part because long strands of DNA are quite fragile.
Japanese researchers have built a large genome from two existing bacterial chromosomes. But Venter, Hamilton Smith, and their colleagues at the J. Craig Venter Institute in Rockville, Maryland, started with short pieces of DNA that a company had manufactured base by base. About 6000 bases long, these pieces represented overlapping bits of the microbe's only chromosome. Some of the pieces also contained "watermarks": a few extra or different bases here and there that distinguish an artificial chromosome from a natural one.
To link the pieces, Smith and Venter's team used enzymes that allowed them to join longer and longer DNA strands until they had just four, each representing one-quarter of the genome. Finally, the team inserted these quarters into yeast, which copied and combined them into a complete chromosome. The researchers sequenced their newly constructed genome and, except for the watermarks, it matched M. genitalium's exactly. The work is "a technical tour de force" and a "monumental effort," says yeast biologist Jef Boeke of Johns Hopkins University School of Medicine in Baltimore, Maryland. However, to be sure this genome works as it should, the researchers must still put it into a DNA-less M. genitalium, notes Eckard Wimmer, a molecular virologist at Stony Brook University in New York state: "Proof is biological function, and that's missing in this paper."
http://sciencenow.sciencemag.org/cgi/content/full/2008/124/3?etoc
ScienceNOW Daily News
24 January 2008
Researchers have rebuilt an entire genome from scratch, they report online today in Science. Although the team has yet to demonstrate that this DNA can substitute for the real thing, the work paves the way for customized bacteria that could efficiently produce drugs, biofuels, and other molecules useful to humankind.
Ever since his group decoded the genome of Mycoplasma genitalium, a parasitic bacterium that lives in the human urogenital tract, sequencing maverick J. Craig Venter has wanted to remake the bug's genome in the lab. At just under 600,000 bases, M. genitalium sports the smallest known genome for a free-living organism, and Venter hoped that an artificial genome could be modified to turn the bacterium into a living chemical-manufacturing plant.
Last year, Venter and his colleagues developed a technique for replacing M. genitalium's genome with another natural genome from a different species (Science, 3 August 2007, p. 632). But synthesizing the M. genitalium genome from the ground up proved challenging, in part because long strands of DNA are quite fragile.
Japanese researchers have built a large genome from two existing bacterial chromosomes. But Venter, Hamilton Smith, and their colleagues at the J. Craig Venter Institute in Rockville, Maryland, started with short pieces of DNA that a company had manufactured base by base. About 6000 bases long, these pieces represented overlapping bits of the microbe's only chromosome. Some of the pieces also contained "watermarks": a few extra or different bases here and there that distinguish an artificial chromosome from a natural one.
To link the pieces, Smith and Venter's team used enzymes that allowed them to join longer and longer DNA strands until they had just four, each representing one-quarter of the genome. Finally, the team inserted these quarters into yeast, which copied and combined them into a complete chromosome. The researchers sequenced their newly constructed genome and, except for the watermarks, it matched M. genitalium's exactly. The work is "a technical tour de force" and a "monumental effort," says yeast biologist Jef Boeke of Johns Hopkins University School of Medicine in Baltimore, Maryland. However, to be sure this genome works as it should, the researchers must still put it into a DNA-less M. genitalium, notes Eckard Wimmer, a molecular virologist at Stony Brook University in New York state: "Proof is biological function, and that's missing in this paper."
http://sciencenow.sciencemag.org/cgi/content/full/2008/124/3?etoc
Universal Influenza Vaccine Tested Successfully In Humans
ScienceDaily (Jan. 25, 2008) — The British-American biotech company Acambis reports the successful conclusion of Phase I trials of the universal flu vaccine in humans. The universal influenza vaccine has been pioneered by researchers from VIB and Ghent University. This vaccine is intended to provide protection against all ‘A’ strains of the virus that causes human influenza, including pandemic strains. Therefore, this vaccine will not need to be renewed annually.
Flanders Institute for Biotechnology (2008, January 25). Universal Influenza Vaccine Tested Successfully In Humans. ScienceDaily. Retrieved January 28, 2008, from http://www.sciencedaily.com /releases/2008/01/080124185522.htm
Flanders Institute for Biotechnology (2008, January 25). Universal Influenza Vaccine Tested Successfully In Humans. ScienceDaily. Retrieved January 28, 2008, from http://www.sciencedaily.com /releases/2008/01/080124185522.htm
International Team to Sequence 1000 Genomes
By Jocelyn Kaiser
ScienceNOW Daily News
22 January 2008
Just a year after the first individual human genomes were sequenced, an international team announced today that it will probe the entire genomes of about 1000 people. The aim is to create the most detailed catalog yet of human genetic diversity to help biomedical researchers home in on disease genes.
The 1000 Genomes Project will delve much deeper than the three celebrity genomes completed last year, including those of genome researcher J. Craig Venter and DNA co-discoverer James Watson (ScienceNOW, 4 September 2007). It will build on the recently completed HapMap, which describes how blocks of DNA tagged by common variants, called single-nucleotide polymorphisms (SNPs), vary in different populations (ScienceNOW, 26 October 2005). These SNPs have turned up more than 100 new DNA markers associated with common illnesses such as diabetes and heart disease (Science, 21 December 2007, p. 1842). But the HapMap includes only the most common markers, those present in at least 5% of the population.
To find rarer SNPs that occur at 1% frequency, genome leaders say, they need to sequence about 1000 genomes. The 3-year project, which will cost $30 million to $50 million, will take advantage of new technologies that have slashed the cost of sequencing. The work will be funded by the U.S. National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, the Sanger Institute in Hinxton, U.K., and the Beijing Genomics Institute in Shenzhen, China.
The consortium will start with three pilot projects. One will exhaustively sequence the entire genome of six individuals: two adults and both sets of their parents. A second project will sequence 180 individual genomes at light coverage, leaving gaps. The third project will fully sequence the protein-coding regions of 1000 genes (5% of the total) in about 1000 genomes. The samples, all anonymous and with no clinical information, will mainly be drawn from those collected for the HapMap, which includes people of European, Asian, and African descent. The first data from the pilot projects should become public later this year.
The new catalog could help disease gene hunters in several ways. It will potentially eliminate the need to sequence around a newly discovered disease SNP to find the variant that actually alters the gene product, says NHGRI Director Francis Collins. The project will also catalog genes that are sometimes lost or duplicated--such copy-number variants can cause disease. By compiling rarer variants, the project should also help resolve a debate about the relative contribution of these mutations to disease risks. Most disease SNPs found so far raise risk only 50% or less, for example, and some researchers suspect that there are rarer SNPs that raise risk twofold, threefold, or more. "There's no question it's going to be a tremendous resource," says Yale University's Judy Cho, who has used the HapMap to find a new gene for Crohn's disease.
ScienceNOW Daily News
22 January 2008
Just a year after the first individual human genomes were sequenced, an international team announced today that it will probe the entire genomes of about 1000 people. The aim is to create the most detailed catalog yet of human genetic diversity to help biomedical researchers home in on disease genes.
The 1000 Genomes Project will delve much deeper than the three celebrity genomes completed last year, including those of genome researcher J. Craig Venter and DNA co-discoverer James Watson (ScienceNOW, 4 September 2007). It will build on the recently completed HapMap, which describes how blocks of DNA tagged by common variants, called single-nucleotide polymorphisms (SNPs), vary in different populations (ScienceNOW, 26 October 2005). These SNPs have turned up more than 100 new DNA markers associated with common illnesses such as diabetes and heart disease (Science, 21 December 2007, p. 1842). But the HapMap includes only the most common markers, those present in at least 5% of the population.
To find rarer SNPs that occur at 1% frequency, genome leaders say, they need to sequence about 1000 genomes. The 3-year project, which will cost $30 million to $50 million, will take advantage of new technologies that have slashed the cost of sequencing. The work will be funded by the U.S. National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, the Sanger Institute in Hinxton, U.K., and the Beijing Genomics Institute in Shenzhen, China.
The consortium will start with three pilot projects. One will exhaustively sequence the entire genome of six individuals: two adults and both sets of their parents. A second project will sequence 180 individual genomes at light coverage, leaving gaps. The third project will fully sequence the protein-coding regions of 1000 genes (5% of the total) in about 1000 genomes. The samples, all anonymous and with no clinical information, will mainly be drawn from those collected for the HapMap, which includes people of European, Asian, and African descent. The first data from the pilot projects should become public later this year.
The new catalog could help disease gene hunters in several ways. It will potentially eliminate the need to sequence around a newly discovered disease SNP to find the variant that actually alters the gene product, says NHGRI Director Francis Collins. The project will also catalog genes that are sometimes lost or duplicated--such copy-number variants can cause disease. By compiling rarer variants, the project should also help resolve a debate about the relative contribution of these mutations to disease risks. Most disease SNPs found so far raise risk only 50% or less, for example, and some researchers suspect that there are rarer SNPs that raise risk twofold, threefold, or more. "There's no question it's going to be a tremendous resource," says Yale University's Judy Cho, who has used the HapMap to find a new gene for Crohn's disease.
Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse: PNAS | January 22, 2008 | vol. 105 |
Infection with cagA-positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. Despite these CagA activities that contribute to neoplastic transformation, a causal link between CagA and in vivo oncogenesis remains unknown. Here, we generated transgenic mice expressing wild-type or phosphorylation-resistant CagA throughout the body or predominantly in the stomach. Wild-type CagA transgenic mice showed gastric epithelial hyperplasia and some of the mice developed gastric polyps and adenocarcinomas of the stomach and small intestine. Systemic expression of wild-type CagA further induced leukocytosis with IL-3/GM-CSF hypersensitivity and some mice developed myeloid leukemias and B cell lymphomas, the hematological malignancies also caused by gain-of-function SHP-2 mutations. Such pathological abnormalities were not observed in transgenic mice expressing phosphorylation-resistant CagA. These results provide first direct evidence for the role of CagA as a bacterium-derived oncoprotein (bacterial oncoprotein) that acts in mammals and further indicate the importance of CagA tyrosine phosphorylation, which enables CagA to deregulate SHP-2, in the development of H. pylori-associated neoplasms.
[Naomi Ohnishi*, Hitomi Yuasa*, Shinya Tanaka, Hirofumi Sawa, Motohiro Miura*, Atsushi Matsui*, Hideaki Higashi*, Manabu Musashi, Kazuya Iwabuchi¶, Misao Suzuki||, Gen Yamada||, Takeshi Azuma**, and Masanori Hatakeyama*,
*Division of Molecular Oncology, Institute for Genetic Medicine and Division of Chemistry, Graduate School of Science, Health Administration Center, and ¶Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan; ||Center for Animal Resources and Development, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; and **Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan]
[Naomi Ohnishi*, Hitomi Yuasa*, Shinya Tanaka, Hirofumi Sawa, Motohiro Miura*, Atsushi Matsui*, Hideaki Higashi*, Manabu Musashi, Kazuya Iwabuchi¶, Misao Suzuki||, Gen Yamada||, Takeshi Azuma**, and Masanori Hatakeyama*,
*Division of Molecular Oncology, Institute for Genetic Medicine and Division of Chemistry, Graduate School of Science, Health Administration Center, and ¶Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan; ||Center for Animal Resources and Development, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; and **Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan]
Hypertension: Pass on the Salt
John F. Foley
Science Signaling, AAAS, Washington, DC 20005, USA
Salt is well known to promote hypertension, but the mechanisms involved in regulating the tone of arterial smooth muscle are poorly characterized. This is particularly true with regard to our understanding of whether similar or distinct mechanisms are responsible for regulating both basal blood pressure and salt-induced hypertension. Phosphorylation of myosin light chain (MLC) is critical for the vascular constriction that is associated with hypertension. Many receptors promote the phosphorylation of MLC either by stimulating MLC kinase, through the activation of heterotrimeric GTP-binding proteins (G proteins) of the Gq and G11 families, or by inhibiting, through G12 and G13 G proteins, the phosphatase that returns MLC to its inactive form. Wirth et al. produced mice that could be induced by treatment with tamoxifen to lack both Gq and G11 (Gq-G11 KO) or both G12 and G13 (G12-G13 KO) in smooth muscle cells. Treatment with tamoxifen caused an increase in blood pressure in all mice, but whereas the blood pressure of wild-type and G12-G13 KO mice soon returned to basal levels, that of Gq-G11 KO mice became 10 to 15% lower than normal, implicating Gq and G11 in the regulation of basal blood pressure. Treatment of wild-type mice with a salt preparation increased their blood pressure, but Gq-G11 KO and G12-G13 KO mice were unaffected, showing that both sets of G proteins mediate salt-induced hypertension. Mice deficient in LARG, an effector of G12 and G13 found in smooth muscle cells that mediates the inhibition of myosin phosphatase, responded to salt treatment similarly to G12-G13 KO mice. As Schoner discusses in commentary, this study makes possible the development of therapies that could interfere with salt-induced hypertension while leaving basal blood pressure regulation intact.
A. Wirth, Z. Benyó, M. Lukasova, B. Leutgeb, N. Wettschureck, S. Gorbey, P. rsy, B. Horváth, C. Maser-Gluth, E. Greiner, B. Lemmer, G. Schütz, J. S. Gutkind, S. Offermanns, G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat. Med. 14, 64-68 (2008). [PubMed]
W. Schoner, Salt abuse: The path to hypertension. Nat. Med. 14, 16-17 (2008). [PubMed]
Citation: J. F. Foley, Pass on the Salt. Science Signaling 1, ec23 (2008).
Science Signaling, AAAS, Washington, DC 20005, USA
Salt is well known to promote hypertension, but the mechanisms involved in regulating the tone of arterial smooth muscle are poorly characterized. This is particularly true with regard to our understanding of whether similar or distinct mechanisms are responsible for regulating both basal blood pressure and salt-induced hypertension. Phosphorylation of myosin light chain (MLC) is critical for the vascular constriction that is associated with hypertension. Many receptors promote the phosphorylation of MLC either by stimulating MLC kinase, through the activation of heterotrimeric GTP-binding proteins (G proteins) of the Gq and G11 families, or by inhibiting, through G12 and G13 G proteins, the phosphatase that returns MLC to its inactive form. Wirth et al. produced mice that could be induced by treatment with tamoxifen to lack both Gq and G11 (Gq-G11 KO) or both G12 and G13 (G12-G13 KO) in smooth muscle cells. Treatment with tamoxifen caused an increase in blood pressure in all mice, but whereas the blood pressure of wild-type and G12-G13 KO mice soon returned to basal levels, that of Gq-G11 KO mice became 10 to 15% lower than normal, implicating Gq and G11 in the regulation of basal blood pressure. Treatment of wild-type mice with a salt preparation increased their blood pressure, but Gq-G11 KO and G12-G13 KO mice were unaffected, showing that both sets of G proteins mediate salt-induced hypertension. Mice deficient in LARG, an effector of G12 and G13 found in smooth muscle cells that mediates the inhibition of myosin phosphatase, responded to salt treatment similarly to G12-G13 KO mice. As Schoner discusses in commentary, this study makes possible the development of therapies that could interfere with salt-induced hypertension while leaving basal blood pressure regulation intact.
A. Wirth, Z. Benyó, M. Lukasova, B. Leutgeb, N. Wettschureck, S. Gorbey, P. rsy, B. Horváth, C. Maser-Gluth, E. Greiner, B. Lemmer, G. Schütz, J. S. Gutkind, S. Offermanns, G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat. Med. 14, 64-68 (2008). [PubMed]
W. Schoner, Salt abuse: The path to hypertension. Nat. Med. 14, 16-17 (2008). [PubMed]
Citation: J. F. Foley, Pass on the Salt. Science Signaling 1, ec23 (2008).
HIV-positive blood donors set record in '07
Blood donors who tested positive for HIV numbered a record 102 in 2007, surpassing 100 for the first time since the HIV antibody test for blood donors began in 1986, according to a Japanese Red Cross Society report Wednesday.
The society's preliminary data found the number of blood donors per 100,000 with HIV also marked a record high of 2.06 in 2007. Meanwhile, the number of total donors recorded its lowest level of 4.94 million in 2007.
Because the tests are only designed to prevent the virus from spreading through donated blood products, the society does not inform donors of the results.
However, a health ministry official said an increasing number of people are donating blood as a free and easy way of getting an HIV test, unaware they will not get the results.
"To prevent the possibility of the virus from spreading, the ministry is urging the public to refrain from blood donation for such purposes," the official said, adding that people should get HIV tests at public health centers or at medical institutions.
The 102 included six people who tested negative for the virus in the society's ordinary blood antibody tests, but ended up being diagnosed as HIV-positive in the society's more highly sensitive virus test.
The number of HIV-positive donors in 2007 was up 15 from the preceding year.
(Source: Japan Times)
The society's preliminary data found the number of blood donors per 100,000 with HIV also marked a record high of 2.06 in 2007. Meanwhile, the number of total donors recorded its lowest level of 4.94 million in 2007.
Because the tests are only designed to prevent the virus from spreading through donated blood products, the society does not inform donors of the results.
However, a health ministry official said an increasing number of people are donating blood as a free and easy way of getting an HIV test, unaware they will not get the results.
"To prevent the possibility of the virus from spreading, the ministry is urging the public to refrain from blood donation for such purposes," the official said, adding that people should get HIV tests at public health centers or at medical institutions.
The 102 included six people who tested negative for the virus in the society's ordinary blood antibody tests, but ended up being diagnosed as HIV-positive in the society's more highly sensitive virus test.
The number of HIV-positive donors in 2007 was up 15 from the preceding year.
(Source: Japan Times)
Croatia opens Tokyo office to promote tourism, ties
The Croatian government has set up a tourism promotion office in Tokyo to meet a sharp increase in Japanese tourists and to deepen bilateral friendship.
According to the Croatia National Tourist Board, which opened the branch, 64,751 Japanese visited the nation in 2006, almost double the previous year's 32,748. The figure rose to 83,346 between last January and November.
The tourism board has set its sights on raising the number by 10 percent from the current level by 2010, the office said in a statement.
The branch will engage in a tourism promotion campaign and provide up-to-date information for visitors.
(Source: Japan Times)
According to the Croatia National Tourist Board, which opened the branch, 64,751 Japanese visited the nation in 2006, almost double the previous year's 32,748. The figure rose to 83,346 between last January and November.
The tourism board has set its sights on raising the number by 10 percent from the current level by 2010, the office said in a statement.
The branch will engage in a tourism promotion campaign and provide up-to-date information for visitors.
(Source: Japan Times)
Innovation distinguishes a leader from a follower: Steve Job
Just got the quote from net and liked it. Thought should save it for sometime in future.
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