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Humans have a bit of shark in them

Jennifer Viegas
Discovery News

Some 450 million years ago, sharks and humans shared a common ancestor, making sharks our distant cousins.

And according to recent research, this kinship is evident in our DNA, as at least one shark species possesses several genes that are nearly identical to those in humans.

The elephant shark's genome is so similar to ours that we wind up having more in common with it, genetically speaking, than with other species, such as teleost (bony skeleton) fishes, which are nearer to us on the evolutionary tree.

"This was a surprising finding, since teleost fish and humans are more closely related than the elephant shark is to humans," says lead author Associate Professor Byrappa Venkatesh.

Venkatesh, principal investigator at the Institute of Molecular and Cell Biology in Singapore, and his team determined that sets of genes on chromosomes, as well as actual genetic sequences, are "highly similar in the elephant shark and human genomes".

The researchers not only analysed the elephant shark genome, but also the genes for other animals including puffer fish, chickens, mice and dogs.

Their findings were recently published in the journal PLoS Biology.

The researchers identified 154 genes in humans that have comparable matches in mice, dogs and elephant sharks.

The similarities between people, mice and dogs were expected, given that they are all mammals.

But sharks are cartilaginous fish that seem to bear little physical resemblance to mammals...

Immunune system genes

The researchers also found that shark and human immune systems are very similar, since sharks have all four types white blood cells found in mammals.

Sean Van Sommeran, executive director of the Pelagic Shark Research Foundation in California, says that he was not entirely surprised to learn about the shark-human links.

"The field of genetics is a Pandora's box," Van Sommeran says.

[This and the following article are grouped - since the Cerebellum appeared in the emergence of species with the sharks. Therefore, evolutionary and comparative PostGenetics ("Genomics beyond Genes") may consider the entire genomes (and specific sets of genes) but also may "zoom" on well-identified neuronal networks and even cell(s), the Purkinje neuron, as its development is governed by "similar" (not identical) genomic information. - Pellionisz, 31st of May, 2007]

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Researchers discover gene essencial to cerebellum formation

By Institute for Research in Biomedicine (IRB)

A study published this week in the scientific journal PNAS provides new information on the origin of different cells in the cerebellum, an important component of the central nervous system found in all vertebrates, including humans, and the part of the brain that controls movement. The study was completed by researchers from the Institute for Research in Biomedicine (IRB Barcelona), the Department of Cell Biology of the University of Barcelona (UB), the IMIM-Hospital del Mar, Pompeu Fabra University (UPF) and Vanderbilt University (Nashville, Tennessee, USA). The main authors of the study are Dr. Marta Pascual (IRB Barcelona and UB) and Ibane Abasolo (IMIM-Hospital del Mar-UPF).

Co-author of the study, Francisco X. Real, coordinator of the Research Unit on Cell and Molecular Biology at IMIM-Hospital del Mar and Professor at the UPF, explains that this discovery sheds new light on the mechanisms of brain formation and has potential future applications for regenerative medicine. It provides crucial insight into the manipulation of truncal nerve cells (or stem cells) and their selective differentiation into 'gabergic' neurons, or cells that contain the neurotransmitter gamma-aminobutyric acid (GABA) and that act as inhibitors.

Eduardo Soriano, Principal Investigator of the Developmental Neurobiology and Regeneration laboratory at IRB Barcelona, and professor at the UB, maintains that the study explains two important principles: first, that the protein Ptf1a/p48 is needed for the production and differentiation of Purkinje neurons, the most important cells in the cerebellum; and second, that in the absence of this protein, the progenitor cells that should produce Purkinje neurons do not differentiate correctly and instead produce a different type of neuron, granular cells, indicating that Ptf1a/p48 acts as a molecular switch.

The researchers hypothesized that a transcription factor, whose function is well known in the pancreas and which appears to play a role in the nervous system, is also involved in the development of the cerebellum. In order to test their idea, and characterize the new mechanism of cell differentation, the authors used mice with a disactivated gene that codes for the Ptf1a/48 protein, and compared them with mice that express the gene normally. Their conclusions provide new insight into origin of nerve cells that form the cerebellum in higher organisms.

In a second research project, led by Francisco Real and Eduardo Soriano and funded by the Fundació La Caixa, the scientists aim to explore the potential of this gene to produce Purkinje neurons in a laboratory setting. The researchers will investigate whether the expression of Ptf1a/p48 can induce the production of Purkinje cells from stem cells and neurospheres, progenitor cells of adult neurons. This study is an important step toward understanding rare diseases, such as cerebellar ataxias, which is characterized by the degeneration of Purkinje cells. Producing this type of cell in the lab may lead to future neuronal replacement therapy.

[This author opened the "Pandorra box" of POSTgenetics (Genomics beyond Genes) by making experimentally verified quantitative predictions for the cerebellar Purkinje cells in the fugu fish, as compared to zebra fish and mammals such as the guinea pig, mouse and human. It would be most interesting to see if/how ptf1 is found in the newly sequenced elephant shark and how the arborization of the Purkinje neuron of the cerebellum of elephant shark would appear - Comment by A. Pellionisz, 31st of May, 2007]

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Astrophysicists Find Fractal Image Of Sun's 'Storm Season' Imprinted On Solar Wind

[Our Sun found to be fractal (left), algorithmically fractal planets, Earth from the Moon - and a real bacterium showing fractality ... AJP]

Science Daily — Plasma astrophysicists at the University of Warwick have found that key information about the Sun’s 'storm season’ is being broadcast across the solar system in a fractal snapshot imprinted in the solar wind. This research opens up new ways of looking at both space weather and the unstable behaviour that affects the operation of fusion powered power plants.

Fractals, mathematical shapes that retain a complex but similar patterns at different magnifications, are frequently found in nature from snowflakes to trees and coastlines. Now Plasma Astrophysicists in the University of Warwick’s Centre for Fusion, Space and Astrophysics have devised a new method to detect the same patterns in the solar wind.

The researchers, led by Professor Sandra Chapman, have also been able to directly tie these fractal patterns to the Sun’s ‘storm season’. The Sun goes through a solar cycle roughly 11 years long. The researchers found the fractal patterns in the solar wind occur when the Sun was at the peak of this cycle when the solar corona was at its most active, stormy and complex – sunspot activity, solar flares etc. When the corona was quieter no fractal patterns were found in the solar wind only general turbulence.

This means that fractal signature is coming from the complex magnetic field of the sun.

This new information will help astrophysicists understand how the solar corona heats the solar wind and the nature of the turbulence of the Solar Wind with its implications for cosmic ray flux and space weather.

These techniques used to find and understand the fractal patterns in the Solar Wind are also being used to assist the quest for fusion power. Researchers in the University of Warwick’s Centre for Fusion, Space and Astrophysics (CFSA) are collaborating with scientists from the EURATOM/UKAEA fusion research programme to measure and understand fluctuations in the world leading fusion experiment MAST (the Mega Amp Spherical Tokamak) at Culham. Controlling plasma fluctuations in tokamaks is important for getting the best performance out of future fusion power plants.

The research by K.Kiyani, S. C. Chapman, B. Hnat, R. M. Nicol, is entitled "Self- similar signature of the active solar corona within the inertial range of solar wind turbulence" and was published on May 18th 2007 in Phys. Rev. Lett.

How Google wants to know everything about you [Searching in your Junk?]

From Times OnlineMay 23, 2007

Google wants to monitor the queries each individual taps into its search site to advise them on their life decisions

Rhys Blakely

Google says it does not yet “know enough about you” and is stepping up its efforts to collect personal information on the web.

Eric Schmidt, the Google chief executive, said yesterday that the world’s biggest internet search engine is still at a “very early” stage when it comes to gathering your personal data through the web. “This is the most important aspect of Google's expansion,” he added.

He envisaged a day when Google would be able to advise its users on everything from their career moves to how they should spend their free time, based on the collected queries they tap into Google.com.

Google already holds a vast amount of personal information about its users – ranging from the contents of e-mail (from its Gmail service) to credit card details (through Google checkout, its online payment system). The information is held in a vast network of massive “server farms” – the company's fleet of digital data centres into which it is estimated to have pumped billions of dollars.

Such information is key to success in the online advertising industry, the source of Google's massive wealth. The No1 aim is to build up precise portraits of individual consumers to better target campaigns.

As it seeks to broaden its information net, it emerged yesterday that Google is also backing a firm founded by the wife of Sergey Brin, the company’s billionaire co-founder, that aims to help people browse their genetic information online.

Google said the investment was made as the start-up 23andMe’s “goal of developing new ways to help people make sense of their genetic information will help us further our mission of organising the world’s information in this new and important field”.

Google invested about $4 million (£2 million) in the company, co-founded by Anne Wojcicki in 2006.

It is not alone among technology companies aiming to tap the human genome – perhaps the most personal information there is. Larry Ellison, the billionaire software behind Oracle, the database giant, last week told Times Online that he plans to store, track and manipulate consumers’ digital data – including their bank details, their medical records, even their genetic blueprints.

Health companies, for instance, given the opportunity to mine this information using Oracle technology, will be able to pinpoint the most effective drugs for individual patients, he suggested.

“We are getting close to this level of personalisation,” he said, citing work being done in Oracle’s labs.

On another front, applied to credit card and telephone records, a similar meeting of personal data and technology will help the authorities do a “better job in finding terrorists,” Mr Ellison said. The extension of predictive modeling techniques, already used to track markets on Wall Street, to areas such as healthcare “will help make societies more efficient,” he predicted.

Meanwhile, Autonomy, a Cambridge-based search technology specialist, has said it is exploring online “transaction hijacking”, where consumers buying items online are automatically informed, during their transaction, if a better price is offered elsewhere.

A Google spokesman stressed to Times Online that Mr Schmidt’s most recent comments referred only to the company’s web-search histories. Moreover, users have to opt in to Google's new "personalised search" tools and the company says it will not pass data on to third parties - unless ordered to do so by law.

Earlier this year, Google bowed to privacy concerns when it agreed to limit the time it keeps information about internet searches to two years.

However, the idea of Google – or any other company – taking a “big brother” role on the web will leave many civil libertarians feeling uneasy.

Data leaks have already sparked fears over personal information that can be gleaned from search behaviour. Last year, for instance, AOL, the internet portal that is part-owned by Google, accidentally released details of 20 million private search queries from 658,000 of its users to the online public.

The collection, quickly disseminated across the web by bloggers, provides a disturbingly intimate picture of some of AOL's user base. Alongside searches for Angelina Jolie and Britney Spears, darker queries typed into the AOL search engine included: "how to tell your family you're a victim of incest" and "how to kill your wife".

Potentially incriminating entries included: "cocaine in urine".

TechCrunch, a blog, said at the time: "The utter stupidity of this is staggering ... The data includes personal names, addresses, social security numbers and everything else someone might type into a search box."

Genome Is Larger and More Complex Compared to Fruit Fly and Mosquito Species That Carries Malaria

Scientists at J. Craig Venter Institute Publish Draft Genome Sequence From Aedes aegypti, Mosquito Responsible for Yellow Fever, Dengue Fever

ROCKVILLE, Md., May 17 /PRNewswire-USNewswire/ -- The fight against yellow fever and dengue fever was advanced today by an international team of researchers led by Vishvanath Nene, Ph.D. of the J. Craig Venter Institute who sequenced the Aedes aegypti genome, the mosquito that carries these deadly diseases. The research was published in the journal "Science."

This research is the first characterization of the approximately 1.38 billion base pairs of DNA of the Ae. aegypti genome. From this sequence, the team showed that this mosquito species has an estimated 15, 419 protein encoding genes.

Since both the sequence of the fruit fly, Drosophila melanogaster (sequenced in 1999 and published in 2000) and another mosquito species, Anopheles gambiae, (sequenced and published in 2002) were available, researchers were able to compare these insects to Ae. aegypti to ascertain biological differences between the species.

An. gambiae diverged on the evolutionary tree from the fruit fly about 250 million years ago, and the two mosquito species diverged from one another approximately 150 million years ago. Genomic comparisons revealed greater differences between the fruit fly and the mosquito species, than between the two mosquito species.

An important finding from this analysis is the discovery of certain proteins and genes unique to the Ae. aegypti. These proteins and genes, among many things, infer robustness to the insect. A more thorough analysis of these genes and proteins may lead to improved means to eradicate the mosquito and thereby stop the spread of yellow and dengue fevers.

Another key discovery was that almost 50 percent of the genome consisted of transposable elements. These are movable pieces of DNA that cause mutations and can affect genome size. The researchers showed that likely due to these elements the gene length and the intergenic regions of Ae. aegypti are 4-6 times larger than those of An. gambiae and the fruit fly.

[Scientific American - notorious of their ill-understanding the field of "non-coding DNA" - breaks the same news under this totally misleading title:

Genetic Code of Deadly Mosquito Cracked

No. The genetic code has not been "cracked". The book has been "revealed", but still those thinking in terms of "junk DNA" can not read any of the 2.5 Billion letters but about the same number of genes that is also present from the lowliest creatures up to the genome of humans (1.3% in the human genome)].

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Rosetta Genomics Receives First Ever Patent Supporting MicroRNA-Based Diagnostics and Therapeutics

Company Expects Further Precedent Setting Issuances to Follow

REHOVOT, Israel and NORTH BRUNSWICK, New Jersey, May 15, 2007 /PRNewswire-FirstCall/ -- Rosetta Genomics, Ltd. (NASDQ: ROSG), a leading microRNA company, announced today that on May 15, 2007, the United States Patent and Trademark Office (USPTO) issued Rosetta Genomics U.S. Patent No. 7,217,807. This is the first microRNA composition of matter patent ever issued relating to a human or viral microRNA gene, and the company believes that this issuance sets an important precedent for Rosetta Genomics' entire target patent portfolio.

The patent covers composition of matter directed at a specific microRNA gene found in the Human Immunodeficiency Virus (HIV). The company believes that this patent, as well as the hundreds of other viral and human microRNA-related patent claims filed by the company worldwide, constitutes a broad intellectual property estate surrounding a new class of prospective drug targets with significant therapeutic opportunity. Targeting microRNAs provides the unique potential to either up- or down-regulate key disease causing proteins. The potential to up- or down-regulate protein expression broadly across this prospective target class is a significant advantage. Human and viral microRNA targets are expected to play a role in the regulation of key disease processes in major therapeutic areas such as oncology, metabolism and infectious diseases.

"This is truly a precedent setting event for validating our extensive portfolio in microRNA genes for both therapeutics and diagnostics," said Ranit Aharonov, Ph.D., Executive Vice President IP & Computational Biology at Rosetta Genomics Ltd. "Rosetta Genomics is the first commercial entity to receive a patent on a microRNA gene. Given we have another patent which has been allowed, and many others in active examination, we feel confident that we will continue to see issuances of our patents for both human and viral microRNA gene sequences as well as patents covering microRNA biomarkers and our cutting-edge enabling technologies. We view the USPTO's decision to issue this patent as strong validation of our position as a leader in this rapidly expanding field. "

"This is a landmark occasion for us", said Amir Avniel, President and CEO of Rosetta Genomics Ltd. "This is a significant step towards validating Rosetta Genomics' leadership role in terms of our microRNA intellectual property estate. Moreover, we believe the issuance of this patent, and future such patents, will allow exclusive partnership opportunities and increases the value proposition across our broad product development pipeline for microRNA-based diagnostics and therapeutics."

About microRNAs

MicroRNAs (miRNAs) are a recently discovered, naturally occurring form of RNAi. These small RNAs act as protein regulators and have the potential to form the basis for a new class of diagnostics and therapeutics. Since many diseases are caused by the abnormal activity of proteins, the ability to selectively regulate protein activity through microRNAs could provide the means to treat a wide range of human diseases. In addition, microRNA expression levels have been shown to be correlated with various disease states and to hold significant potential as diagnostics and prognostic markers

About Rosetta Genomics

Rosetta Genomics is a leader in the development of microRNA-based diagnostics and therapeutics. Founded in 2000, the company's integrative research platform combining bioinformatics and state-of-the-art laboratory processes has led to the discovery of hundreds of biologically validated novel human microRNAs. Building on its strong IP position and strategic alliances with leading biotechnology companies, Rosetta Genomics is working to develop a full range of diagnostic and therapeutic products based on microRNAs. The company's primary focus is in the development of microRNA-based products to diagnose and treat different forms of cancer and infectious diseases.

USPTO 7,217,807 Bioinformatically detectable group of novel HIV regulatory genes and uses thereof

The invention claimed is:

1. An isolated nucleic acid consisting of 77 up to 120 nucleotides, wherein the nucleic acid comprises the sequence of SEQ ID NO: 14.

2. An isolated nucleic acid wherein the sequence of the nucleic acid consists of the sequence of SEQ ID NO: 14.

3. A vector comprising an HIV nucleic acid insert, wherein the nucleic acid insert consists of the nucleic acid of claim 1 or claim 2, and wherein said vector does not comprise an HIV nucleic acid insert other than the nucleic acid of claim 1 or claim 2.

4. A probe comprising an HIV nucleic acid insert, wherein the nucleic acid insert consists of the nucleic acid of claim 1 or claim 2, and wherein said probe does not comprise an HIV nucleic acid insert other than the nucleic acid of claim 1 or claim 2.

5. An isolated nucleic acid complement of the nucleic acid of claim 1 or claim 2, wherein said isolated nucleic acid complement is identical in length to the nucleic acid of claim 1 or 2.

[Viral microRNA] - Cancer Virus' Genetic Targets Identified

Science Daily — University of Florida researchers have identified specific human genes targeted by a virus believed to cause Kaposi's sarcoma, a rare form of cancer associated with AIDS and with organ transplants that causes patches of red or purple tissue to grow under people's skin.

Writing May 11 in PLOS Pathogens, the scientists are the first to name human genes that are actually hijacked by a virus wielding minimolecules called microRNAs. Apparently the viral microRNAs silence genes known to influence growth of blood vessels and suppress tumor cells. Scientists believe that with the regulatory genes sidelined, blood vessel growth runs rampant, resulting in the typical markings of Kaposi's sarcoma.

"The hallmarks of Kaposi's sarcoma are red spots full of blood vessels on the necks, arms and legs of patients," said Rolf Renne, Ph.D., an associate professor of molecular genetics and microbiology at the College of Medicine and a member of the UF Shands Cancer Center and the UF Genetics Institute. "We think that the tumor virus is using microRNAs to make sure infected cells are well nourished and protected from the human immune system."

Thought to be little more than cellular debris less than a decade ago, microRNAs are short chemical strands that strategically silence gene activity by binding to RNA within cells. They play a role in healthy development -- no one with a complete set of fingers and toes would want their genes to keep adding new digits -- and they evidently may be involved in the onset of some diseases, including cancer.

Now it seems that even foreign microRNA has a say in human health.

In an effort to identify human gene targets, UF scientists equipped cultured human cells with just 10 genes from the Kaposi's sarcoma virus, thus endowing human cells with the ability to produce viral microRNA. Scientists then screened the more than 30,000 genes that exist within human cells and found that 81 were strongly inhibited in the presence of the viral microRNA.

Five of the most affected genes are known to suppress tumor and blood vessel growth and influence the body's immune response, suggesting that the herpesvirus uses microRNA to create a cancerous environment in which it thrives, undetected by the body's natural defenses.

Researchers confirmed the results of the microRNA gene profiling with tests to detect individual microRNA activity in specific genes. "The data beautifully showed which genes were regulated by the viral microRNA," said Henry Baker, Ph.D., a professor and interim chairman of molecular genetics and microbiology who oversaw the gene screening. "The most exciting thing was one of the most-targeted genes on the list is thrombospondin 1. When something is important in a natural process, there are often a lot of built-in redundancies. In this case all of the viral microRNAs were used to target 34 different binding sites on the human gene, so apparently this is a virus that really wants to down-regulate thrombospondin."

ABSTRACT Kaposi sarcoma–associated herpesvirus (KSHV) is a gamma-herpesvirus associated with Kaposi sarcoma, primary effusion lymphoma, and a subset of muticentric Castleman disease. Recently, it was found that KSHV encodes 12 microRNAs (miRNAs) within its latency-associated region. miRNAs are small 22 nucleotide-long single-stranded RNA molecules that act to inhibit gene expression by binding to target messenger RNAs (mRNAs). Because miRNAs bind to these targets with limited base pairing, it has been difficult to find targets. The goal of our study was to identify cellular mRNAs targeted by KSHV-encoded miRNAs. Microarray analysis of cells expressing the KSHV miRNAs revealed a set of 81 genes that were changed. Several genes are regulators of important functions such as blood vessel growth, cell proliferation, and cell death. One target, thrombospondin 1, is a potent inhibitor of blood vessel growth and is known to be down-regulated in Kaposi sarcoma tumors. Thrombospondin 1, which is targeted by multiple miRNAs, also showed reduced protein levels in our study. To our knowledge, our data describe the first targets for tumorvirus-encoded miRNAs and suggest that these novel regulators may have roles in pathogenesis.

Is the universe a fractal? [With the DNA no exception to the universe? - AJP]

09 March 2007
New Scientist

Written across the sky is a secret, a hidden blueprint detailing the original design of the universe itself.

The spread of matter throughout space follows a pattern laid out at the beginning of time and scaled up to incredible proportions by nearly 14 billion years of cosmic expansion.

Today that pattern is gradually being decoded by analysing maps of the distribution of the stars, and what has been uncovered could shake modern cosmology to its foundations. Cosmology is founded on the assumption that when you look at the universe at the vastest scales, matter is spread more or less evenly throughout space. Cosmologists call this a "smooth" structure.

But a small band of researchers, led by statistical physicist Luciano Pietronero of the University of Rome and the Institute of Complex Systems, Italy, argues that this assumption is at odds with what we can see.

Instead they claim that the galaxies form a structure that isn't smooth at all: some parts of it have lots of matter, others don't, but the matter always falls into the same patterns, in large and small versions, at whatever scale you look. In other words, the universe is fractal.

It is a controversial view, and one that sparked an intense debate over a decade ago. Since then, astronomers have surveyed ever-greater numbers of galaxies, taking larger and larger samples of the universe. Now the biggest galaxy survey ever and a brand new map of the universe's dark matter are adding fuel to the fire.

At stake is far more than the way galaxies cluster. A fractal universe could undermine cosmology's most basic assumptions. "All of the observations we make depend to a greater or lesser extent on the idea that the universe is homogeneous," says David Hogg of New York University, who leads a team of physicists that disputes Pietronero's view.

This idea that matter is spread more or less evenly throughout the universe is embodied in Einstein's cosmological principle. Einstein formulated it after publishing his general theory of relativity, which describes how the distribution of mass bends space-time and creates gravity. It allows cosmologists to use the equations of general relativity to describe the geometry of the whole universe. As a result it has led to a picture of a universe expanding uniformly from the big bang and in which cosmological measurements have defined meanings.

Fractals allow Pietronero to paint a very different sort of picture - one in which the irregular distribution of matter that we see around us never evens out into a smooth structure, but repeats itself at ever grander scales.

Fractals are familiar enough: we see them in the branching of trees, the curves of coastlines, lungs, turbulence and clouds. No matter what scale you look at them, fractal patterns look the same.

Think of broccoli: a tiny branch looks much the same as the whole vegetable. Zoom in or zoom out, the structure looks the same - exquisitely detailed, never smooth. Fractals can be beautiful to look at, but when it comes to galaxies it may be a subversive kind of beauty. Certainly the universe does not look smooth. Some regions contain clusters of matter; others are virtually empty.

Hundreds of billions of stars group together to form galaxies, and galaxies congregate in clusters. Clusters assemble into colossal structures called superclusters that can stretch out for 100 million light years and look uncannily like fractal patterns. Even superclusters string together in long filaments and sheets that stretch like ghostly cobwebs across an otherwise empty sky. The Sloan Great Wall, for example, which was discovered in 2003, spans more than a billion light years. These filaments and sheets seem to encircle huge voids of empty space. The voids range from 100 to 400 million light years in diameter, making the whole assemblage appear as an immense, glowing lattice punctuated by wells of darkness.

No one disputes that the universe is far from smooth on relatively small scales - by which cosmologists mean thousands of light years. But Hogg's team is convinced that if you zoom further out, smoothness reigns. "When you're looking at the size scales of galaxies, groups of galaxies, clusters, superclusters and filaments, it looks like a fractal," says Hogg. "But once you get larger than all of that, then it starts to look homogeneous."

What has convinced him is his team's analysis of the latest data from the Sloan Digital Sky Survey, the largest 3D map of the galactic universe so far. His team insists that the map is proof of smoothness.

The fractal camp, however, are skeptical. In fact, they say the Sloan observations confirm what they've been claiming all along. It might appear to be deadlock, but at least with the Sloan survey the two sides can agree what they're disagreeing about.

For years Pietronero and his team argued that the statistical methods mainstream cosmologists were using to establish homogeneity were flawed because they start off by assuming that matter is evenly spread. The team was mostly ignored until 2004, when Hogg and astrophysicist Daniel Eisenstein of the University of Arizona in Tucson spent a summer in Paris with Pietronero's colleagues, cosmologists Francesco Sylos Labini of the Enrico Fermi Centre and the Institute for Complex Systems, Rome, and Michael Joyce of the Pierre and Marie Curie University, Paris.

"We argued every day about fractals," Hogg says. "Those battles raged over lunch and coffee and finally convinced us by the end of our visit that we should be doing the analysis as they say." When they returned to the US, Hogg and Eisenstein applied the fractal team's methods to a sample of 55,000 luminous red galaxies mapped by Sloan.

They found that the galaxies do form a fractal pattern, but as they looked at bigger and bigger scales, the pattern appeared to disintegrate and smooth out at just over 200 million light years - a scale far larger than most cosmologists had expected.

But Pietronero and Sylos Labini are not convinced. Instead, they believe that if astronomers could continue to zoom out and look at even larger scales, they would find more clustering. They suspect that the apparent smoothness at 200 million light years is not real, but rather an illusion created by statistical effects due to the limited range of the Sloan survey. Hogg's team, though, insist that their evidence of homogeneity is statistically significant. "I think the result really is secure," says Hogg. "I would stake my scientific reputation on that."

Even if the result is real, mainstream cosmologists still have a huge problem on their hands. The fact that the fractal patterning extends to far bigger scales than anyone had expected means that there must be far bigger structures than anyone expected - structures that are even bigger than superclusters.

The fractal team argues that the standard model cannot explain the existence of these galactic giants. "If you look at the galaxy data, you can see enormous objects hundreds of millions of light years across, stuff that's really huge," says Pietronero.

"This is a huge problem. You're going to have to change the story very radically." The usual story runs something like this. In the tiny fluctuations of the nascent universe, matter began to collect in denser regions, setting off a chain reaction of gravitational collapse that has given us the large-scale structure we see today. Gravity has worked from the bottom up, building galaxies first, then collecting galaxies into clusters, then clusters into superclusters and so forth. But while the matter has been clumping together, the universe has been expanding, and thus a battle has ensued: gravity versus expansion.

According to Pietronero, there simply hasn't been enough time since the universe came into being 14 billion years ago for gravity to sculpt structures larger than about 30 million light years across: expansion would have prevented anything larger from forming. "The existence of structures much larger than this implies a crisis of the present view of structure formation," he says. This present view is the "cold dark matter model", in which the glowing masses of stars and galaxies are only the tip of the cosmic iceberg. Luminous matter makes up roughly 15 per cent of all the matter in the universe - the other 85 per cent is mysterious dark matter. Hogg's team says that the new observations do not undermine the standard view as Pietronero claims. Instead, they maintain that the cold dark matter model explains the Sloan data quite accurately. For that to be true, however, Hogg's team have to put a number called a bias parameter into their equations. It reflects the difference between the distribution of matter in computer simulations of the cold dark matter model and the observed distribution of luminous matter. Collisions between particles of ordinary matter help it clump together, but dark matter is thought not to behave in the same way. That suggests it could be spread out in space more evenly than ordinary matter, so cosmologists assume that the distribution of the matter we can see - galaxies, say - is not a true reflection of the distribution of all the matter that is out there.

They believe the structure of the universe is really much "smoother" than it appears to be, because dark matter dominates. In the case of the Sloan survey, the bias is 2: the visible galaxies are clumped twice as densely as the predicted total distribution of matter in the universe. Sylos Labini, however, sees the bias as a fudge that allows cosmologists to discount the observed clustering of galaxies and to assume that the gigantic clusters of superclusters are only half the problem they appear to be. "The bias is a way to hide the size of structures behind some ad hoc parameter," he says. Mainstream cosmologists, however, feel the bias is justified, assuming that galaxies cluster in regions of space that are replete with excess dark matter. According to the standard model, dark matter is everywhere, but galaxies only shine in the rare regions where dark matter is densest. Dark matter also lingers in the voids where no light shines but here it is thinly spread out. In other words, while the luminous galaxies look very clustered, the underlying blanket of dark matter is far smoother, supporting the claim of homogeneity. "If the cold dark matter model is correct, then there should be dark matter in the voids," Hogg says.

The million-dollar question is: what is the real distribution of dark matter?

Is dark matter smooth or fractal? Is it clustered like the galaxies, or does it spread out, unseen, into the great voids? If the voids are full of dark matter, then the apparent fractal distribution of luminous matter becomes rather insignificant. But if the voids are truly empty, the fractal claim requires a closer look. Astronomers are now providing our first glimpse into the voids and our first look at the pattern of invisible matter. Richard Massey of the California Institute of Technology in Pasadena and others in the Cosmic Evolution Survey project have just created the first 3D map of dark matter in the universe (New Scientist, 13 January, p 5). They were able to find the dark matter by observing its gravitational effect on any light streaming past it. Combining data from the Hubble Space Telescope, the Subaru telescope in Hawaii and the Very Large Telescope in Chile, they mapped the distribution of dark matter at scales ranging from 23 million to 200 million light years across. Massey's team found that the dark matter distribution is nearly identical to the luminous matter distribution. "The first thing that strikes me is the voids," Massey says. "Vast expanses of space are completely empty. The dark matter makes up a criss-crossing network of strings and sheets around these voids. And all the luminous matter lies within the densest regions of dark matter."

Although this distribution of dark matter seems to favour the idea that the universe is fractal, Hogg isn't convinced. "It is interesting," he says, "but measurements of dark matter are much less precise than measurements of galaxy distributions." "The result is very new," Massey agrees. "It demonstrates a very exciting new way of looking directly at dark matter and will be vital in future work, but hasn't yet been subject to all the analysis that has been applied to galaxy surveys." When asked if the dark matter exhibits an explicitly fractal structure, Massey replies, "We don't know yet."

"The universe is not a fractal," Hogg insists, "and if it were a fractal it would create many more problems that we currently have."

A universe patterned by fractals would throw all of cosmology out the window. Einstein's cosmic equations would be tossed first, with the big bang and the expansion of the universe following closely behind. Hogg's team feel that until there's a theory to explain why the galaxy clustering is fractal, there's no point in taking it seriously. "My view is that there's no reason to even contemplate a fractal structure for the universe until there is a physical fractal model," says Hogg. "Until there's an inhomogeneous fractal model to test, it's like tilting at windmills." Pietronero is equally insistent. "This is fact," he says. "It's not a theory." He says he is interested only in what he sees in the data and argues that the galaxies are fractal regardless of whether someone can explain why. As it turns out, there is one model that may be able to explain a fractal universe. The work of a little-known French astrophysicist named Laurent Nottale, the theory is called "scale relativity" (see "Fractured spacetime"). According to Nottale, the distribution of matter in the universe is fractal because space-time itself is fractal. It is a theory on the fringe, but if the universe does turn out to be fractal, more people might sit up and take notice. A resolution to the fractal debate will only come with more data. Sloan is currently charting more galaxies and will release a new map in the middle of 2008. According to Sylos Labini, this will cover over 650 million light years and should tell us if the apparent transition to homogeneity extends beyond 200 million light years. For now, the pattern of the world, imprinted at the origin of the universe, remains a secret glimpsed only in the knowing shimmer of the stars.

Fractured space-time

French astrophysicist Laurent Nottale has developed a theory that takes fractals to a whole new level. A researcher at the Meudon Observatory in Paris, Nottale set out to extend Einstein's principle of relativity - in which the laws of physics remain the same regardless of the motion of an observer - to a theory in which the laws of physics would remain the same regardless of the scale at which the universe is being observed. He found that the underlying space-time of such a theory would have to be fractal. In Nottale's theory, called scale relativity, the underlying fractality of space-time is most noticeable in the quantum world. Quantum behaviour, he claims, can be understood geometrically - particles move along fractal trajectories. On large scales, his model could explain a fractal pattern of the galaxies. The most profound question in physics today is how to unify the really small with the really big - and when it comes to matters of scale, fractals may turn out to be a key ingredient.

Opossum Provides Insight into Human Evolution

First Decoded Marsupial Genome Reveals "Junk DNA" Surprise

Stefan Lovgren

for National Geographic News

May 10, 2007

The genome of a marsupial—the tiny short-tailed opossum (Monodelphis domestica)—has been sequenced for the first time.

The study reveals a surprising role in human evolution for "jumping genes"—parasitic bits of "junk DNA" that until now were thought to be nothing more than a nuisance—and may also lead to a number of medical breakthroughs.

In particular, the study highlights the genetic differences between marsupials such as opossums and kangaroos and placental mammals like humans, mice, and dogs.

Marsupials typically spend their youths tucked in a mother's pouch, while placental females maintain a temporary organ called the placenta to nourish their embryos.

"The opossum is a wonderful comparison to the human," said Eric Lander, director of the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts, which led the sequencing project.

The study, which appears in today's issue of the journal Nature, helps to explain the evolutionary origins of human DNA, Lander pointed out. (Read a genetics overview.)

And opossums are often used as models in a wide variety of research on human health and disease, including the malignant melanoma form of skin cancer. (Related: Macaque Genome Deciphered; May Herald Medical Breakthroughs" [April 12, 2007].)

The new findings show that marsupials have a much more complex immune system than previously thought.

Jumping Genes

Marsupials are the closest living relatives of placental mammals. The two groups split from a common ancestor about 180 million years ago.

Scientists were able to pinpoint the genetic elements that are present in placental mammals but missing from marsupials to learn more about what makes the two groups different.

The researchers were surprised to find that placental and marsupial mammals have largely the same set of genes for making proteins. Instead, much of the difference lies in the controls that turn genes on and off.

"Twenty percent of all the regulatory instructions in the human genome were invented after we part ways with the marsupials," Lander said.

"That was the first really important surprise about evolution—it's tinkering much more with the controls than it is with the genes themselves."

The scientists were also surprised to find that these regulatory sequences have in large part been distributed across the human genome by so-called jumping genes.

These genes have hopped through chromosomes for more than a billion years, leaving behind many copies of themselves. So until now the genes had been widely regarded by scientists as parasites, or "junk DNA," that played no creative role in evolution.

"It was a surprise that quite a significant proportion of all the new regulatory controls in the genome were coming from jumping genes," Lander said.

"It looks like [they are] a pretty major force for evolutionary innovation."

Advanced Immune System

The short-tailed opossum is native to South America and is also known as the Brazilian opossum and rain forest opossum.

The individual whose genome was sequenced came from a colony housed at the Southwest Foundation for Biomedical Research in San Antonio, Texas.

The animals have many features that make them ideal for scientific research, especially during early development, experts point out.

"Their biology is fascinating," said Jenny Grace, a biologist and marsupial expert at the Australian National University (ANU) in Canberra.

"Their young are born very tiny, the size of a penny."

The creatures are the only other mammals known to develop melanoma skin cancer solely from exposure to ultraviolet light, the cause of melanoma in most human cases.

Newborn opossums can also repair damage to their spinal cords, making them a focus of research into regenerative medicine.

"This shows us that it may not be that hard to grow spinal cords," said Lander, the Broad Institute director.

"Once you have a marsupial that can do something that a human or mouse can't do, you can compare the two," he added. "We're saying, wait, wait, it may not be that hard to grow spinal cords. Our closest cousins can do it. Let's see what tricks [they] have."

Scientists had also believed that marsupials have a primitive immune system.

"The genome project knocked that firmly on its head," ANU's Grace said.

"It turns out that marsupials have a very complicated immune system. It's just different from us."

Thursday, May 10, 2007

Led by researchers from Harvard and MIT, a team of scientists sequenced the DNA of the gray South American short-tailed opossum -- the first marsupial to have its genome sequenced.

Marsupials are closely related to placental mammals, the group that includes humans, but their evolutionary lines diverged 180 million years ago during the dinosaur age.

Interestingly, the team found that the majority of differences were found not in genes coding for proteins, but in the non-coding regions that has been popularly described as "junk DNA".

A fifth of the human genome's key functional elements arose after the divergence from marsupials, the research found. Most of these innovations occurred not in protein-coding genes but in areas of the genome that do not contain genes and until recently [until International PostGenetics Society formally abandoned the misnomer "Junk" DNA - AJP] had been derided as junk DNA, they found.

[Science Daily] ... It has been the regulation of their genes - when they turn on and off - that has changed dramatically.

"Evolution is tinkering much more with the controls than it is with the genes themselves," said Broad Institute director Eric Lander. "Almost all of the new innovation ... is in the regulatory controls. In fact, marsupial mammals and placental mammals have largely the same set of protein-coding genes. But by contrast, 20 percent of the regulatory instructions in the human genome were invented after we parted ways with the marsupial."

The research, released Wednesday (May 9) also illustrated a mechanism for those regulatory changes. It showed that an important source of genetic innovation comes from bits of DNA, called transposons, that make up roughly half of our genome and that were previously thought to be genetic "junk."

The research shows that this so-called junk DNA is anything but, and that it instead can help drive evolution by moving between chromosomes, turning genes on and off in new ways.

The research - the first time a marsupial genome was decoded - involved the gray, short-tailed opossum, a native of South American rain forests that is small enough to fit in the palm of one's hand. Marsupials, which include kangaroos and koalas, have young that do much of their development in a pouch outside the mother's body instead of in an interior womb as in humans and other "placental mammals."

It had been initially thought that most of a creature's DNA was made up of protein-coding genes and that a relatively small part of the DNA was made up of regulatory portions that tell the rest when to turn on and off.

As studies of mammalian genomes advanced, however, it became apparent that that view was incorrect. The regulatory part of the genome was two to three times larger than the portion that actually held the instructions for individual proteins.

"The official textbook picture of how genes work really didn't appear to be right," Lander said. "There was much more of the genome standing around shouting instructions than actually producing proteins."

That raised a question of how evolution actually works on the genome, Lander said. With so much of the genome devoted to regulation, it became apparent that evolution could work by simply changing the instructions rather than changing the protein-coding genes themselves.

The opossum genome provided an important point of comparison because it is more distantly related to humans than other mammals whose genomes had been studied. While the common ancestor of humans and opossums split 180 million years ago, the common ancestor of humans and mice split just 80 million years ago.

The research will also prove useful for those seeking to understand opossum biology, according to other researchers involved in the project. Opossums are important models for human disease studies because they're the only animal other than humans who develop melanoma - skin cancer - after exposure to ultraviolet radiation. They are also used in nervous system research because baby opossums can regenerate their spinal cord tissue after it is cut and regain the ability to move their limbs.

[Los Alamos] Genome Institute Reaches Milestone with a Mighty Microbe [to neutralize Uranium pollution]

Shewanella baltica OS185 is a tiny, ocean-dwelling microbe that could be an answer to cleaning up certain kinds of radioactive contamination, but for a few days this month the microbe is in the spotlight at Los Alamos for another reason. Los Alamos scientists working as part of the Department of Energy's Joint Genome Institute (JGI) recently finished the genetic code of Shewanella baltica OS185 as its 100th genomic sequence.

Finishing a genome is the process of finding and eliminating any gaps in sections of genetic code that were not initially sequenced correctly by automated sequencing methods.

"The finishing of S. baltica is being celebrated as a Los Alamos milestone for a couple reasons," said Chris Detter, leader of the JGI Sequencing Technology Team, "Not only is it our 100th completed genomic sequence, but it's also appropriate because S. baltica has shown potential for use in confining and cleaning up uranium-contaminated areas, such as the Laboratory's legacy waste sites. The microbe might someday be put to work right here at Los Alamos for the bioremediation of uranium contamination at nuclear waste sites because of its unique abilities."

While solid in most forms, uranium can break down over time in the natural environment leading to the possible contamination of groundwater. Taken from the depths of the Baltic Sea, the S. baltica microbe has a unique ability to convert uranium dissolved in groundwater into an insoluble form called uranium dioxide, or uraninite, which prevents the uranium from mixing with water and from migrating into and with groundwater flows.

Los Alamos specializes in developing techniques to take raw sequence data from the high-throughput JGI facility in Walnut Creek, California, and transform it into finished genomes. The Laboratory began finishing sequences for JGI in 2003. Making advancements in genome technology and chemistry over the years, more components of the process have become automated, speeding up finishing rates as a result.

In addition to Detter, other leaders in the JGI-LANL include David Bruce, Tom Brettin, and Cliff Han, and 35 exceptional scientists, technicians, and support staff.

The Next Human Genome Project: Our Microbes [MetaGenomics and PostGenetics; Common computer algorithms]

George Weinstock, Baylor University, Houston, TX

By Emily Singer
Wednesday, May 02, 2007

A proposed project to sequence the microorganisms that inhabit our bodies could have a huge impact on human health.

Much as we might like to ignore them, microbes have colonized almost every inch of our bodies, living in our mouths, skin, lungs, and gut. Indeed, the human body has 10 times as many [kind of?] microbial cells as human cells. They're a vital part of our health, breaking down otherwise indigestible foods, making essential vitamins, and even shaping our immune system. Recent research suggests that microbes play a role in diseases, such as ulcers, heart disease, and obesity.

While microbes make up such an intimate part of us, most of our microbial inhabitants remain a mystery. The bacteria in the human body are very difficult to study, since only about 1 percent of them can be grown in the lab. Now a proposed new project to sequence all our microbial residents could change that.

"This is completely unexplored territory that is likely to have a large impact on our understanding of human health and disease," says George Weinstock, codirector of the Human Sequencing Center at the Baylor College of Medicine, in Houston. "We hadn't been able to approach it because of the scale of the problem. But now we are finally able to open that door."

Thanks to ever-improving methods to sequence DNA, scientists can now analyze the genomes of entire microbial communities, a field known as metagenomics. By comparing microbial communities in people of different ages, origins, and health statuses, researchers hope to find out precisely how microorganisms prevent or increase risk for certain diseases and whether they can be manipulated to improve health.

Several metagenomics projects are under way or have been completed, including analysis of the microbes living in the human gut and on the skin. But a true snapshot of our microbial menagerie will require a massive effort, along the lines of the Human Genome Project. "Even though a microbial genome is one-thousandth the size of the human genome, the total number of microbial genes in [the human] body is much greater than human genes because you have so many different species," says Weinstock.

The National Institutes of Health (NIH) is now considering such a project. Metagenomics experts and government officials met last week to determine if the proposal, dubbed the human microbiome, will become an NIH "Roadmap" initiative. These NIH-wide programs identify major gaps in biomedical research and provide financial support on a much larger scale than typical grants. A final decision is expected this month.

"At the end of the day, we'll end up with another perspective on the evolution of our species, our human-microbial selves," says Jeffrey Gordon, a microbiologist at the Washington University School of Medicine, in St. Louis.

Recent research from Gordon's lab hints at the potential public-health impact of a clearer understanding of our microbial tenants. Gordon and his colleagues have shown that obese people harbor different microbial communities than lean people. And as obese people lost weight, their microbes began to look more like their lean counterparts' microbes.

Researchers aren't yet sure what triggers the differences, but they found in a similar study in mice that the microbial populations of obese mice could more effectively release calories from food during digestion than could microbes of their lean littermates.

While exciting, Gordon's research also illustrates the challenges of cataloging microbes. To truly interpret the human microbiome, scientists will need to look at the variation in microbial communities among many people and a variety of populations. Complicating the problem is that, while an individual's human genome is static, a person's microbial composition--and thus his or her microbiome--fluctuates over time. So an accurate picture of one person's microbiome could require multiple resequencing efforts.

These types of studies could yield the biggest reward, revealing whether different organisms are correlated with different health states. Gordon and others hope that a microbial analysis will ultimately become a routine part of medical exams, perhaps used to diagnose different diseases.

Scientists are still debating whether the microbiome will become a road-map project, and if so, what the final goals of the project will be: should they focus on generating complete sequences of dominant microbes, for example, or devote equal energy to the complex task of studying microbial variation?

In the meantime, microbiologists are getting ready. Three large sequencing centers--at Baylor, the Broad Institute, and Washington University--have garnered funding to sequence the genomes of a few of the gut microorganisms that can be grown in the lab, which will be crucial in later studies. Ultimately, says Gordon, "we'll get a much more transcendent view of ourselves as a supraorganism with traits acquired from our microbial partnerships."

MicroRNA found in unicellular organism

Yijun Qu, China's National Istitute of Biological Sciences

BEIJING, April 30 (UPI) -- A Chinese-led international team of scientists has, for the first time, identified microRNAs in a unicellular organism.

The team, led by Yijun Qi of China's National Institute of Biological Sciences, made the discovery in green alga Chlamydomonas reinhardtii.

"The finding changes the dogma that miRNAs only exist in multicellular organisms and adds an important piece into the blooming small RNA world," said Qi. "A pressing question we have now is what these miRNAs are exactly doing in the green alga. I hope we will know the answers soon."

The finding shows unicellular miRNAs share functional characteristics with plant miRNAs, in so far as they can direct the cleavage of target mRNAs in vitro and in vivo.

Furthermore, the scientists found miRNA expression patterns changed during gamete differentiation, suggesting a possible role in regulating sexual reproduction.

The discovery also has evolutionary implications, suggesting the miRNA pathway arose before the lineages split. The lack of universally conserved miRNA genes in algae, plants and animals suggests they might have evolved independently.

The research is to appear in the May 15 issue of Genes & Development.

Mouse microRNA knockout uncovers critical roles in immune system

A role for a microRNA in the immune system has been shown by study of one of the world's first microRNA knockout mouse, reported Friday 27 April in Science. The microRNA acts as a lynchpin to balance the response of immune defences and the researchers suggest the corresponding human gene will have a similar vital role.

Cells of the immune system in the knockout mice do not work as well as normal cells and the mice develop symptoms similar to those of human autoimmune disease. They are also less able to resist infection by bacteria, such as Salmonella. The team suggest that the equivalent human microRNA will play a major role in the human immune system.

MicroRNAs are copied from DNA but do not contain code for protein. Rather, they are themselves active in controlling the activity of other genes, often by inducing destruction of protein-coding messenger RNAs or by preventing their activity in the cell.

The research team, led by the Wellcome Trust Sanger Institute, targeted a gene called Bic/microRNA-155 (or miR-155) in embryonic stem cells which they used to transfer the mutation into mice. [Correction for journalists, see bottom: iBic is a gene from which the microRNA-155 is derived from. MicroRNA-s are NOT genes - AJP]. Previous research showed that miR-155 was active in cells of the immune system and overactivity was found in lymphoma development.

"Very little is known about the function of the hundreds of microRNA genes," [genes associated with particular microRNA - AJP] said Dr Antony Rodriguez, lead author on the paper from the Wellcome Trust Sanger Institute. "Although plentiful, this class of genes had never before been knocked out in mice, the best model organism for human disease."

"But we simply did not know whether microRNA knockouts would have an effect in mice: previous knockout studies in nematode worms suggested that most microRNAs were not essential. Our findings were dramatically different."

The effects of the miR-155 knockout swept across the immune system. The team showed that, although knockout of miR-155 did not appear to affect normal growth and development of cells in the immune system, each major cell type - T-cells, B-cells and dendritic cells - performed less well.

"These findings demonstrate the importance of this level of control in the immune system and will lead immunologists to rethink how the immune system works," said Dr Martin Turner, Head of the Laboratory of Lymphocyte Signalling and Development at the Babraham Institute.

The deficits in response were significant: the knockout mice were less able to resist infection by bacteria than mice with normal miR-155, producing lower levels of antibody and a reduced response by T-cells. They also develop changes to lung tissue, with scarring that is similar to some human systemic autoimmune disorders...

"This dramatic finding reflects a large amount of work by collaborating groups," said Professor Allan Bradley, Director of the Wellcome Trust Sanger Institute. "Showing that knocking out a microRNA has such dramatic effects opens new doors to understanding this novel class of gene regulation, with consequences for human health and disease."

"Our work builds upon the sequences of the human and mouse genomes, the power of computer analysis and microarray work and exemplifies why whole-organism research can bring understanding that cannot be developed in any other way."...

MicroRNAs and BIC

MicroRNAs (also known as siRNAs - short, interfering RNAs) are short (22-25 base) sequences that do not code for protein, [that is, MicroRNA-s are "junk" DNA...according to the obsolete terminology - AJP] but can lead to destruction of other RNA molecules or can interfere with their translation. They bind to corresponding bases in the target RNA. The mature microRNAs are derived from larger precursor molecules.

Bic is a non-coding RNA, around 1600 bases in length, which was identified in 1997 as a cancer-causing gene (oncogene) in chickens. The human and mouse versions were discovered in 2001. The BIC gene is activated in cells of the human and mouse immune system and in B-cell lymphomas and some solid tumours.

miR-155 is derived from within the iBic gene and is 65 bases in length: its mature form is 22 bases long. The human equivalent of miR-155 is found on chromosome 21: the mouse and human mature forms of miR-155 differ at one position. To date, some 377 microRNAs have been found in the mouse genome and 474 in the human.

MicroRNAs are being examined as possible therapeutic agents in a range of diseases. Trials are underway for macular degeneration (eye disease), chronic myeloid leukaemia and preeclampsia.

[Stanford] Fire and Mello shared the Nobel Prize for Physiology or Medicine in 2006 for RNAi, which led to discovery of mechanism of action of miRNAs.

[MicroRNA-s are protected intellectual property. Current (average) valuation of a single 21-letter "string" is about $150,000 - but those with direct impact for "Big Pharma" skyrocket; Merck bought SiRNA company for $1.1 Billion - Comment by A. Pellionisz, 28th of April, 2007]

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Japanese Tohoku University International Innovation Forum in Silicon Valley, California

Tohoku University US Office will hold its Opening Ceremony on April 26 and the First Tohoku University International Innovation Forum on April 27 at the Marriott San Mateo at San Francisco Airport , 1770 South Amphlett Boulevard. The US Office is the international promotion center of Tohoku University. The two day event will feature over 50 world renowned experts in their fields speaking on a broad spectrum of science and technology issues to include Nobel Laureate Roger Kornberg, Stanford University Professor, speaking on The Gene Reader in Our Cells. California Governor, the Honorable Arnold Schwarzenegger, is scheduled to present the opening keynote address. The creation of Tohoku’s Silicon Valley California office demonstrates the beginning of its intention to create a portal for the facilitation of collaboration with US companies and educational institutions.

Tohoku US Deputy Director Dr. Toshihiko Nishimura said, “June 2007 will mark the 100th Anniversary of the founding of Tohoku University. It is significant to hold the Opening Ceremony and First International Innovation Forum in the centennial year of 2007. Tohoku University has established unique policies and principles that are “Research First,” “Open Door” and “Practice-Oriented Research and Education.” Our goal for this event is to introduce Tohoku University and showcase its extensive professional and educational achievements, technologies, and intellectual property which are founded on our excellent research and education programs. The goal of the Tohoku University US office is to share and transfer these resources and to contribute to the US industry and society. We want to achieve the position of a world-known university which excels in technology research. We have selected Silicon Valley as the location of our US office, the heartland of technology, from both an academic and commercial perspective.. Our slogan is : Be The Center Of Reference; COR.

More than 50 world renowned experts, in all facets of science and technology including the president, directors, vice directors, deans, and professors from Tohoku University, will attend this event. Delegates from Miyagi Prefecture and Sendai City of Japan and the Federation of Tohoku Economic World will also attend this event. Delegates from the State of California, local counties and cities including government officials and political figures are scheduled to attend this ceremony. Stanford University and University of California will send more than twenty professors to the anniversary ceremony. The Governor of California, the Honorable Arnold Schwarzenegger is scheduled to give a congratulatory speech.

On April 27, Professor Shuji Nakamura, University of California Santa Barbara will open the all-day program of the International Innovation Forum. The 2006 Chemistry Noble Laureate, Roger Kornberg, Stanford University Professor, is the luncheon keynote speaker. Eight sessions are planned for the afternoon. This forum’s philosophy is to introduce Tohoku University’s endeavors to address key current worldwide societal issues in a road show style. Sessions are: environmental issues, energy issues, international pandemic diseases (HIV, Avian Flu), population issues, and issues associated with our aging society.

Tohoku University, being a world leader in the technology fields of Materials Science and Micro Electro Mechanical Systems (MEMS), has created sessions devoted to these topics. The MEMS session will be moderated by world renowned Tohoku University Professor Masayoshi Esashi and will include local Silicon Valley MEMS luminaries including Dr. Kurt Petersen, CEO of SiTime, Roger Howe, Stanford University Professor, Al Pisano, Professor and Director of the University of California Berkeley, Berkeley Sensor and Actuator Center and Masahiko Ogirima, MEMS Core. The Materials Science session will be moderated by Tohoku University Professor Sadamichi Maekawa with panelists including Stuart Parkin of IBM, Robert Sinclair of Stanford University and Masashi Kawasaki of Tohoku University.

Additional sessions include intellectual property collaborations with Tohoku University and future universities collaborations based on the sister city relationship between Riverside and Sendai, Tohoku’s home. At the end of the forum, distinguished US. venture capitalists including Koji Osawa, Co-Founder of Global Catalyst Partners, Steve Domenic, General Partner of Sevin Rosen Funds and James Wei , Co-Founder of Worldview Technology Partners will be joined by Stanford Professor Tom Byers. They will discuss the business vision for universities.

[The RIKEN-based "Genome Network Platform" by Japanese National Institute of Genetics is to help make sure that inside Japan progress keeps abreast with the fierce global competition. Globally, Japan has just established a bridgehead in Silicon Valley, California, with emphatic participation of Stanford and associated Venture Capital groups. Pellionisz, 26th of April, 2007]

[Please welcome the 52nd Founder of IPGS, Dr. Yauchiro Takagi, for his acceptance, keynote lecture and introduction of Nobel Laurate Dr. Kornberg at the 1st Tohoku University International Innovation Forum in Silicon Valley, 27th of April, 2007]

Cure for Alzheimer's: Japanese Vaccine Works On Mice

Reuters; Japan, March 29, 2007

Japanese scientists have developed an oral vaccine for Alzheimer's disease that has proven effective and safe in mice, the director of a research institute behind the project said on Thursday.

The team is preparing to move to small-scale clinical trials in humans, possibly this year, said Takeshi Tabira, director of the National Institute for Longevity Sciences in Aichi, central Japan.

"We hope the Phase I trials go well," Tabira said. "Animals are able to recover their functions after developing symptoms, but humans are less able to do so. It may be that this only works in the early stages of the disease, when symptoms are light."

When administered to mice suffering from the disease, which causes dementia and is currently incurable, the vaccine reduced the amount of amyloid plaques in the brain and improved mental function.

Amyloid plaques are believed to be at the root of Alzheimer's -- a growing problem for ageing populations around the world. The disease affects five million in the United States alone, the Alzheimer's Association said in a report last week.

The treatment did not cause inflammation or bleeding in the brains of the mice, Tabira said. The vaccine is made by inserting amyloid-producing genes into a non-harmful virus. When taken orally, the virus stimulates the immune system to attack and break down the amyloid proteins in the brain, Tabira said.

The treatment was tested on 28 mice genetically modified to develop Alzheimer's disease. Half the animals were given a dose of the vaccine at the age of 10 months, while the control group were not treated.

Three months later, tests showed mental function in the treated mice had returned to levels close to those before they developed Alzheimer's symptoms.

U.S. drugmaker Wyeth and its Irish partner Elan Corp have an Alzheimer's vaccine called ACC-001 in early stage human trials.

The Japanese research, carried out in conjunction with scientists at Nagoya University and others, is to be published by the Federation of American Societies for Experimental Biology in July.

[Eric Mathur] named vice president of the J. Craig Venter Co. [La Jolla]
04/16/2007

Eric Mathur of Carlsbad, ... was recently appointed vice president of the J. Craig Venter Co. in La Jolla, the discoverer of the human genes sequence...

He has been a research scientist at UCR, the Scripps Institute, Stratagene Cloning System Inc. and the Diversa Corporation (as co-founder) and recently was distinguished scientific consultant and research fellow at the J. Craig Venter Institute and its Synthetic Geonomics Inc.

Most of his activities have been and are in the field of rapidly advancing genetic engineering and sciences boundaries.

He has published more than 60 scientific papers, and is named inventor on more than 50 issued U.S. and world patents, and has been invited to present more than 100 scientific lectures.

Mathur's parents immigrated to the United States in the 1940s and 1950s. His mother, a retired Redlands teacher, came from Latvia, and his father, who was a defense research and development engineer with Aerospace Corp. and TRW, came from India.

'Junk' DNA now looks like powerful regulator, Stanford researcher finds

Craig Lowe (UCSC)

STANFORD, Calif. -- Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections, according to a new study by researchers at the Stanford University School of Medicine and the University of California-Santa Cruz. The scientists propose that this redeemed DNA plays a role in controlling when genes turn on and off.

Gill Bejerano, PhD, assistant professor of developmental biology and of computer science at Stanford, found more than 10,000 nearly identical genetic snippets dotting the human chromosomes. Many of those snippets were located in gene-free chromosomal expanses once described by geneticists as "gene deserts." These sections are, in fact, so clogged with useful DNA bits - including the ones Bejerano and his colleagues describe - that they've been renamed "regulatory jungles."

"It's funny how quickly the field is now evolving," Bejerano said. His work picking out these snippets and describing why they might exist will be published in the April 23 advance online issue of the Proceedings of the National Academy of Sciences.

It turns out that most of the segments described in the research paper cluster near genes that play a carefully orchestrated role during an animal's first few weeks after conception. [See the "Methylation prediction of FractoGene" - AJP]. Bejerano and his colleagues think that these sequences help in the intricate choreography of when and where those genes flip on as the animal lays out its body plan. [The vague notion of gene "turn on" is a "turn off" for theorists. No serious computer scientists would ever describe the role of software "to turn bits on and off" in a computer. "Intricate choreography" is better journalism, but still no substitute for hierarchical (recursive) protein synthesis where the fractality of organism is governed by the fractality of DNA - AJP]In particular, the group found the sequences to be especially abundant near genes that help cells stick together. These genes play a crucial role early in an animal's life, helping cells migrate to the correct location or form into organs and tissues of the correct shape.

The 10,402 sequences studied by Bejerano, along with David Haussler, PhD, professor of biomolecular engineering at UC-Santa Cruz, are remnants of unusual DNA pieces called transposons that duplicate themselves and hop around the genome. "We used to think they were mostly messing things up. Here is a case where they are actually useful," Bejerano said.

He suspects that when a transposon is plopped down in a region where it wasn't needed, it slowly accumulated mutations until it no longer resembled its original sequence. The genome is littered with these decaying transposons. When a transposon dropped into a location where it was useful, however, it held on to much of the original sequence, making it possible for Bejerano to pick out.

In past work, Bejerano and his co-workers had identified a handful of transposons that seemed to regulate nearby genes. However, it wasn't clear how common the phenomenon might be. "Now we've shown that transposons may be a major vehicle for evolutionary novelty," he said.

The paper's first author, Craig Lowe, a graduate student in Haussler's lab at UC-Santa Cruz, said finding the transposons was just the first step. "Now we are trying to nail down exactly what the elements are doing," he said.

Bejerano's work wouldn't have been possible without two things that became available over the past few years: the complete gene sequence of many vertebrate species, and fast computers running sophisticated new genetic analysis software. "Right now it's like being a kid in a candy warehouse," Bejerano said. Computer-savvy biologists have the tools to ask questions about how genes and chromosomes evolve and change, questions that just a few years ago were unanswerable. [Correction: they could have been answerable e.g. for human and mouse genomes since 2002 but considering 98.7% "Junk" there was no money to run with suitable software built for computers that did exist. Now even NIH - and EU - start pouring money, but private business will run away with the fat profits just as GenenTech did when "genes" became technologically approachable - AJP]

Bejerano and his colleagues aren't the first to suggest that transposons play a role in regulating nearby genes. In fact, Nobel laureate Barbara McClintock, PhD, who first discovered transposons, proposed in 1956 that they could help determine the timing for when nearby genes turn on and off.

Could US scientists get EU funding?

European Medical Research Councils to discuss allowing US citizens to apply for grants
By Stephen Pincock
[Published 19th April 2007 01:23 PM GMT]

Representatives of Europe's national medical research councils are planning to discuss next week the possibility of letting US scientists apply for European research funding, in the same way that European researchers can receive funding from the US National Institutes of Health.

Liselotte Højgaard, chair of the standing committee of the European Medical Research Councils (EMRC) told The Scientist that during the organization's annual meeting in Stockholm next week, members would discuss a potential white paper on clinical trials in Europe.

One item that might make it into that white paper is the idea of levelling the playing field for US researchers in terms of EU funding, she said. "In my personal opinion the current situation is utterly unfair. I know that I have personally applied for NIH funding [in the past] and have really appreciated it."

Under current arrangements, researchers from outside the US can apply for NIH funding. The NIH website lists 188 grants made in 2007 to researchers based outside of the US, some for close to $1 million.

Researchers based outside of Europe, however, cannot apply for EU funding. At the newly established European Research Council, for example, "funds are open to any scientists (of any nationality) based in the EU," European Commission spokesperson Antonia Mochan said in an Email.

Højgaard, head of the department of clinical physiology and nuclear medicine at Rigshospitalet, Copenhagen University Hospital, was careful to say she couldn't predict the outcome of the debate, which would involve representatives from agencies such as the UK's Medical Research Council, the Deutsche Forschungsgemeinschaft (DFG) in Germany, and INSERM in France among others.

"It's only one small item on a long agenda," she said. "I will ask my fellow medical research council representatives whether it is of their concern also." Denmark is already discussing changing its national law to allow people from outside Europe to apply for research grants, she said.

The Scientist contacted the British, French and German medical research councils for comment. Mark Palmer from the UK's MRC declined to comment until the issue had been discussed by the board; representatives of INSERM and DFG did not return calls by deadline.

Mochan said that EU research commissioner Janez Potocnik and NIH director Elias Zerhouni had discussed the matter informally, but that the European Commission had nothing further to add at this time.

The EMRC was established in 1971. Part of its role is to develop European scientific strategies and stimulate collaboration in emerging and interdisciplinary research areas.

Stephen Pincock

[It is not only a good idea for US researchers to compete for EU research funds ("levelling the field of global competition" in order to break down monopolies of "science establishments"), but it is a formal recognition of the already existing fact that "brain drain" is not as "one-sided" as it used to be. Just as Liselotte Hojgaard quoted her personal case (having applied for US funds from EU), this columnist could quote episodes from his experience, from a complementary viewpoint. Germany has long established the "Senior Distinguished American Scientist Award", in recognition of the US "Marshall Plan" and NASA's application of a paradigm-shift of Neural Networks was quickly followed by awarding the "Alexander von Humboldt Prize" (on German money) to AJP. Likewise, very recently, the "European Inaugural of International PostGenetics Society" in Hungary resulted in awarding to AJP an "European Union Visiting Professorship" - since small new member countries of the EU are unlikely to be able to compete in "Modern Genetics" with established giants such as the UK, Germany, The Netherlands, etc. thus the newly ascended member countries of the EU would like to directly plunge into the "PostModern era of Genetics" (PostGenetics). However, given their meager resources and formidable transitional challenges, they need their US-based researchers to "pitch in" with the EU for the accomplishment of full collective success in PostGenetics. This is quite similar to global cooperation in stem cell research, where notable US-based researches turned to their UK roots to accomplish difficult goals of a paradigm-shift. - A. Pellionisz, 21th of April, 2007]

Genomicists Tackle the Primate Tree

Science, Apr. 13.
Elizabeth Pennisi

Richard Gibbs, Baylor, Houston, Texas

Primates are taking center stage in genomics, with the macaque serving as an early milestone in understanding our relatives' genomes--and therefore our own

The deciphering of the human genome was a humbling experience. The promise of the project, in the words of James Watson, was "to find out what being human is." But even when most of the 3 billion bases of the human genome had been properly placed, much about the sequence defied understanding. Where in the 20,000 human genes uncovered are the ones that set Homo sapiens apart from other mammals, or other primates? To find out, genomicists have been scrambling for more data [in the sciences "data" are the sine qua non" - but without theory, data alone never yield understanding - AJP] ever since, most recently from primates. "The goal is to reconstruct the history of every gene in the human genome," [is it, really? - should it not be an understanding why some human genes may not have a "history" - AJP] says Evan Eichler, a geneticist at the University of Washington, Seattle. And that requires data from our relatives. DNA from different branches of the primate tree will allow us "to trace back the evolutionary changes that occurred at various time points, leading from the common ancestors of the primate clade to Homo sapiens," says Bruce Lahn, a human geneticist at the University of Chicago in Illinois.

In 2005, the unraveling of the chimp genome provided tantalizing hints about differences between us and our closest relative (Science, 2 September 2005, p. 1468). Now ... the third primate genome, that of the rhesus macaque, begins to put the chimp and human genomes into perspective. Macaques are Old World monkeys, which split perhaps 25 million years ago from the ape lineage that led to both chimpanzees and humans.... So when compared to apes, monkeys can help identify the more primitive genetic variants, allowing researchers to tease out the changes that evolved only in apes. Researchers want to take such analyses back to even more ancient evolutionary divergences, and so seven more primate genome sequences are under way, as is the sequencing of the DNA of two close nonprimate relatives. Together, these genomes "should teach us general principles of primate evolution," says Lahn. [They "should" but don't be surprised if "comparative genomics" may not yield clues unless and until we define *what* we are "comparing" - AJP]

A consortium of more than 100 researchers who have been unraveling the macaque genome are detecting genes that have changed faster than expected in the chimp and human lineages; such speed is usually a telltale sign of significance in evolution. They are also finding that dozens of base changes known to put humans at risk for disease also exist in the healthy macaque--but not in the chimpanzee. That suggests that some gene variants implicated in disease are relics of the ancestral primate condition. Such studies "may be the bridge between comparative genomics and evolutionary biology," says Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center in Houston, Texas, and coordinator of the rhesus macaque genome project. [Here you go! There is a specific theoretical hypothesis lurking here; that the emergence of species is hierarchical, and a lapse back into an "outgrown" phase is not only "obsolete" but may be a harmful "glitch" - AJP]

Gibbs and his colleagues are tackling evolutionary biology in reverse. They are identifying key genomic differences without yet knowing how or whether those differences translate into traits that provide survival advantages. Traditionally, researchers have first traced changes in the shapes and sizes of beaks, bodies, brains, and so on, then sought the genes behind them. The hope is that the two modes of inquiry will meet in the middle. But so far researchers have come up short in linking genomic changes to traits subjected to natural selection and other evolutionary forces, ironically because of sparse biological data on nonhuman primates, says glycobiologist Ajit Varki of the University of California, San Diego: "[Without] basic information about the chimp, its physiology, its diseases, its anatomy, you are really very impoverished about what you can say."

Beyond mouse

In 2001, the human genome sequence drove home how little we knew about our genomic selves. About one-third of our genes were complete unknowns. Researchers immediately started lining up our DNA with that of worms, fish, and rodents to see what genes matched up and to try to pin down functions. They found not just genes but also conserved regions within the "junk" DNA that played as critical a role in genome function as the genes themselves. Their finds led to an unquenchable thirst for sequence data as a way to clarify how genomes work. "Every additional species increases our ability to resolve functional from nonfunctional [DNA]," explains Ross Hardison, a molecular biologist at Pennsylvania State University in State College.

The surprise of the chimp genome, the first nonhuman primate to be sequenced, was the large number of insertions and deletions that differed between humans and our closest living cousins. There were more changes in the order and number of genes and blocks of genes than changes in single base pairs, highlighting the importance of this kind of expansion and shuffling in primate speciation.

But the chimp data proved frustrating as well, because researchers couldn't put the chimp-human comparisons into an evolutionary context. If humans had one base, say a C, at a position where chimpanzees had a G, researchers had no way of knowing which base represented the ancestral condition. [It is much worse, since we can not exclude the theoretical possibility that "neither" - AJP]. Consequently, there was no way to tell whether the change at that position had occurred only in humans--and therefore perhaps helped define Homo sapiens--or in the chimp. And so in 2005, the National Human Genome Research Institute began stuffing more primates into the sequencing pipeline and approved the $20 million rhesus macaque sequencing project. "It is great to finally have a [distant relative] that allows us to assign differences between the human and chimpanzee genomes to either the human or the chimpanzee evolutionary lineage," says Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Sequencers aren't stopping at the macaque. Sequencing of many primates, including the orangutan, the gibbon, and a New World monkey, the marmoset, is under way, with promises that the baboon should be next. In 2006, the Wellcome Trust Sanger Institute in Hinxton, U.K., started deciphering the gorilla genome, planning coverage similar to that of the macaque. Meanwhile, genomicists have started sequencing key genes and regulatory regions from other primates, too. "To tell what is human-specific, you need this comparative context," says Anne D. Yoder, an evolutionary biologist at the Duke Lemur Center in Durham, North Carolina. [When is "enough" "enough"? Never. Venter has just collected (and is sequencing) gezillions of genomes - leading to not only "comparative genomics" but "metagenomics". Even with sequencing getting increasingly dramatically less expensive - the amount of resources going into "data collection" is certainly in the range of hundreds of millions of dollars - while the theorethical efforts, e.g. those advocated by PostGenetics are disproportionally neglected. Trends of sciences suggest that - just as in nuclear physics - quickest advances will occur where data-production (e.g. by smashing nuclear particles) will be at least accompanied, but preferably guided by, quantitative theoretical predictions that are testable by experimentation - AJP]

To know a genome

Already, the primate genomic data are revealing bits of our genetic history. For example, more than 98% of chimp and human bases agree. So researchers hoping to pick out areas with fewer base changes than expected--such as regulatory regions conserved in all apes--are awash in a tide of virtually identical DNA. But when the search is expanded to additional primates, there's more variation in the sequences, and previously undetectable conserved regions, even small regulatory sequences, begin to surface.

For example, Dario Boffelli, now at Children's Hospital Research Center in Oakland, California, and his colleagues at the Joint Genome Institute in Walnut Creek, California, wanted to understand the regulation of genes that help maintain healthy levels of cholesterol in the body. They looked at 558,000 bases covering genes involved in cholesterol processing, comparing human and six other primates: baboon, colobus monkey, dusky titi, marmoset, owl monkey, and squirrel monkey. They discovered regions with virtually the same sequence in all the primates. Subsequent experiments showed that three of the newly identified conserved regions do indeed regulate genes in the cholesterol pathway, Boffelli's team reported in January in Genome Biology.

In other cases, particularly as researchers look for differences that reflect independent evolution, data from even one additional primate can help. In one analysis, the macaque team looked at 64,000 places in the macaque genome where they knew a disease-related mutation existed. In the past, researchers have assumed that such mutations were specific to humans. A few chimp genes had hinted that some problematic bases might predate humans, but the macaque drives home how often this may be the case. Hardison and his Pennsylvania State colleague Webb Miller found more than 200 sites where the macaque had the same base at the same position as the diseased or at-risk human. In 97 instances, both the chimp and the macaque matched the aberrant human base; in 48 cases it was just the chimp. And in 84 cases the rhesus, but not the chimp, matched the diseased human sequence, possibly because chimps also independently evolved away from the ancestral condition at those sites.

For example, about 1 in 15,000 people have phenylketonuria because their gene for an enzyme needed to process the amino acid phenylalanine is defective. Untreated, the buildup of a toxic byproduct causes mental retardation. In macaques, that same defective gene is the normal condition and has no ill effects. It could be that many "disease" variants in humans are simply ancestral variants "where [a dietary or environmental] change between the human ancestor and the human has made a variant that used to be good, bad," says Miller.

In addition, the macaque genome consortium combed the macaque, chimp, and human genomes for families of genes that had expanded in one or more species. A family consists of the original gene and any subsequent copies, many of which evolve slightly different sequences and functions over time.

One in particular intrigued Miller. This family, called PRAME--short for "preferentially expressed antigen of melanoma"