DNA clue to honey bee deaths

Scientists say that mass bee deaths may be caused by viruses that disrupt gene expression.

The team analysed which genes were turned on and which were turned off in healthy bees and those from hives with colony collapse disorder (CCD).

Since 2006, CCD has caused the catastrophic loss of US bee hives and is implicated in bee deaths elsewhere.

Writing in PNAS journal, the team say they used "whole genome microarrays" to compare cells from bees' guts.

Lead scientist May Berenbaum from the University of Illinois told BBC News that the research was made possible by publication of the bee genome in 2006.

We talk about a smoking gun. We have the bullet hole! Professor May Berenbaum

"It's an incredibly useful repository of information which allowed the construction of the microarray - a slide which has all 10,000 bee genes on it," she said.

"We used it to compare colony collapse disorder bees with healthy ones and looked at the differences. There are of course 10,000 genes. So there were a whole lot of differences but we could rule out many of them."

Gut feeling

The team concentrated on analysing gene expression from cells in the bees' guts because this is the primary site of pesticide detoxification and immune defence.

Previous theories for CCD have included pesticide poisoning as well as infection and mite infestation.

But the team's genetic analysis of the bees' guts failed to reveal elevated expression of pesticide response genes.

In addition, genes involved in immune response showed no clear expression pattern despite the increased prevalence of viruses and other pathogens in CCD colonies.

What did show up in the guts of the CCD bees was an abundance of fragments from the ribosome, a structure which is the cell's protein making factory.

According to the researchers, this finding suggests that protein production is likely to be compromised in bees from CCD hives.

Previous research shows that the viruses that bees carry all attack the ribosome.

Little problem

The microbes in question are known as "picorna-like" viruses. The word derives from pico, which means little, and RNA (ribonucleic acid).

"These picorna-like viruses all attack at the same spot," said Professor Berenbaum.

"What they do is to work their way into the ribosome and instead of making honey bee protein they make virus proteins.

"So maybe what's happening is basically the ribosome wears out. So we looked to see if the CCD bees have more of these viruses than healthy bees. And they do.

The viruses in question include "deformed wing virus" and "Israeli acute paralysis virus".

The scientists believe that if a number of similar picorna-like viruses attack simultaneously, they may be able to overwhelm the ribosome.

"We talk about a smoking gun. We have the bullet hole!" said May Berenbaum.

"We now need to look for how multiple viruses might interact on the ribosome."

The honey bee is the US's key agricultural pollinator. As such it is worth $14bn to the country's economy.

CCD was first identified in 2006. In the winter of 2007-8 more than a third of US bees were lost.

Similar losses have been reported in Europe, giving rise to fears that CCD is a global problem.

http://news.bbc.co.uk/1/hi/sci/tech/8219202.stm

40 years of Unix

The computer world is notorious for its obsession with what is new - largely thanks to the relentless engine of Moore's Law that endlessly presents programmers with more powerful machines.

Given such permanent change, anything that survives for more than one generation of processors deserves a nod.

Think then what the Unix operating system deserves because in August 2009, it celebrates its 40th anniversary. And it has been in use every year of those four decades and today is getting more attention than ever before.

Work on Unix began at Bell Labs after AT&T, (which owned the lab), MIT and GE pulled the plug on an ambitious project to create an operating system called Multics.

The idea was to make better use of the resources of mainframe computers and have them serve many people at the same time.

"With Multics they tried to have a much more versatile and flexible operating system, and it failed miserably," said Dr Peter Salus, author of the definitive history of Unix's early years.

Time well spent

The cancellation meant that two of the researchers assigned to the project, Ken Thompson and Dennis Ritchie, had a lot of time on their hands. Frustrated by the size and complexity of Multics but not its aims of making computers more flexible and interactive, they decided to try and finish the work - albeit on a much smaller scale.

The commitment was helped by the fact that in August 1969, Ken Thompson's wife took their new baby to see relatives on the West Coast. She was due to be gone for a month and Thompson decided to use his time constructively - by writing the core of what became Unix.

He allocated one week each to the four core components of operating system, shell, editor and assembler. It was during that time and after as the growing team got the operating system running on a DEC computer known as a PDP-7 that Unix came into being.

By the early 1970s, five people were working on Unix. Thompson and Ritchie had been joined by Brian Kernighan, Doug McIlroy and Joe Ossanna.

The name was reportedly coined by Brian Kernighan - a lover of puns who wanted Unics to stand in contrast to its forebear Multics.

The team got Unix running well on the PDP7 and soon it had a long list of commands it could carry out. The syntax of many of those commands, such as chdir and cat, are still in use 40 years on. Along with it came the C programming language.

But, said Dr Salus, it wasn't just the programming that was important about Unix - the philosophy behind it was vital too.

"Unix was created to solve a few problems," said Dr Salus, "the most important of which was to have something that was much more compact than the operating systems that were current at that time which ran on the dinosaurs of the computer age."

Net benefits

Back in the early 1970s, computers were still huge and typically overseen by men in white coats who jealously guarded access to the machines. The idea of users directly interacting with the machine was downright revolutionary.

"It got us away from the total control that businesses like IBM and DEC had over us," said Dr Salus.

Word about Unix spread and people liked what they heard.

"Once it had jumped out of the lab and out of AT&T it caught fire among the academic community," Dr Salus told the BBC. What helped this grassroots movement was AT&T's willingness to give the software away for free.

That it ran on cheap hardware and was easy to move to different machines helped too.

"The fact that its code was adaptable to other types of machinery, in large and small versions meant that it could become an operating system that did more than just run on your proprietary machine," said Dr Salus.

In May 1975 it got another boost by becoming the chosen operating system for the internet. The decision to back it is laid out in the then-nascent Internet Engineering Task Force's document RFC 681, which notes that Unix "presents several interesting capabilities" for those looking to use it on the net.

It didn't stop there. Unix was adapted for use on any and every computer from mainframes to desktops. While it is true that it did languish in the 1980s and 90s as corporations scrapped over whose version was definitive, the rise of the web has given it new life.

The wars are over and the Unix specification is looked after by the Open Group - an industry body set up to police what is done in the operating system's name.

Now Unix, in a variety of guises, is everywhere. Most of the net runs on Unix-based servers and the Unix philosophy heavily influenced the open source software movements and the creation of the Linux desktop OS. Windows runs the communication stack created for Unix. Apple's OS X is broadly based on Unix and it is possible to dig into that software and find text remarkably similar to that first written by Dennis Ritchie in 1971.

"The really nice part is the flexibility and adaptability," said Dr Salus, explaining why it is so widespread and how its ethic fits with a world at home with the web.

"Unix is the best screwdriver ever built," said Dr Salus.

http://news.bbc.co.uk/1/hi/technology/8205976.stm

Oestrogen can be used to treat breast cancer

While estrogen-lowering drugs are currently used to treat breast cancer, a new study shows that estrogen itself can fight the tumor in those suffering a comeback.

Previous studies had reported that drugs such as tamoxifen and the aromatase inhibitors can treat breast malignancy through cutting off the estrogen required for feeding the estrogen-receptor-positive tumors.

According to the study published in the Journal of the American Medical Association, a very low dose of estrogen can treat relapses in 30 percent of women on estrogen-blocking drugs.

It is also reported to be more effective and much better tolerated than chemotherapy.

Failure, however, is noted in 30 percent of those who had previously responded to the treatment. The study, however, showed that going back on the aromatase inhibitors could stop the progression of the cancer in one third of these patients.

"We demonstrated clearly that the low dose was better tolerated than the high dose and was just as effective for controlling metastatic disease," said lead researcher Matthew Ellis.

He added that a high dose of the drug may cause headaches, bloating, breast tenderness, fluid retention, nausea and vomiting.

Scientists concluded that estrogen can be used to treat metastatic hormone-dependent breast cancer in postmenopausal women.

http://www.presstv.ir/detail.aspx?id=103942&sectionid=3510210

The relevant research papers from the journal can be accessed here:

Estradiol in Breast Cancer Treatment: http://jama.ama-assn.org/cgi/content/extract/302/7/797
Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor–Positive, Aromatase Inhibitor–Resistant Advanced Breast Cancer: http://jama.ama-assn.org/cgi/content/short/302/7/774?home

'Dostoevsky mice' cured of epilepsy

Epilepsy may be sparked by a metal imbalance in the brain caused by a singlegene mutation, a study in mice suggests. The finding could help develop new treatments in humans who suffer from the condition.

Steven Clapcote's team at the University of Leeds, UK, pinpointed a gene that seems to play an important part in the genesis of epileptic seizures, which result from abnormal bursts of electrical activity in the brain and can occur even when there is no underlying neurological condition.

The Atp1a3 gene is one of three that produce a chemical pump mechanism to keep sodium and potassium levels in brain nerve cells and the surrounding tissue at the levels needed for normal activity.

"It's been known for a long time that injecting the sodium/potassium pump inhibitor ouabain into the brain can induce seizures in rats," says Clapcote, and it's also known that mice lacking two of three forms of the pump – either the "alpha1" or "alpha2" forms – are free from seizures.

Cured offspring

Clapcote's team have now determined that mice with a mutated copy of theAtp1a3 gene and reduced activity of the "alpha3" pump were prone to epileptic seizures. The mouse strain has been dubbed Myshkin after a Dostoevsky character in The Idiot, who suffered from epilepsy. "Mysh" also comes from the Russian for mouse.

The team could treat some of the symptoms in the Myshkin mice with valproic acid, a standard epilepsy treatment. But the researchers found they could also prevent seizures from occurring completely – at least in the next generation.

They injected DNA fragments containing the normal Atp1a3 gene into mouse eggs to establish a second strain of mice that produced extra copies of the normal alpha3 pump, and crossed them with the Myshkin mice.

"Half of the offspring of this cross had the faulty alpha3 gene from the Myshkin parent," he says. "However, they did not have epilepsy because they also inherited the extra copies – we didn't work out how many – of the normal alpha3 gene from the other parent."

'Ideal tool'

The mouse and human version of the Atp1a3 gene are almost identical, and Clapcote thinks it is a "strong candidate" gene to explain some forms of human epilepsy.

Working with colleagues at the University of Swansea, UK, the researchers have begun to screen DNA from people with epilepsy to search for mutations in the gene. If there's a positive match, the Myshkin mice would be an ideal tool to help in the development and testing of new epilepsy therapies, Clapcote says.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0904817106)

http://www.newscientist.com/article/dn17549-dostoevsky-mice-cured-of-epilepsy.html?DCMP=NLC-nletter&nsref=dn17549

Structure of HIV genome 'decoded'

Scientists say they have decoded the entire genetic content of the HIV-1 virus, a key source of Aids infection.

They hope this will pave the way to a greater understanding of how the virus operates, and potentially accelerate the development of drug treatments.

HIV carries its genetic information in more complicated structures than some other viruses.

The US research, published in Nature, may allow scientists the chance to look at the information buried inside.

HIV, like the viruses which cause influenza, hepatitis C and polio, carries its genetic information as single-stranded RNA rather than double-stranded DNA.

The information enclosed in DNA is encoded in a relatively simple way, but in RNA this is more complex.

We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host Ron Swanstrom study author

RNA is able to fold into intricate patterns and structures. Therefore decoding a full genome opens up genetic information that was not previously accessible, and may hold answers to why the virus acts as it does.

The team from the University of North Carolina at Chapel Hill said they planned to use the information to see if they could make tiny changes to the virus.

"If it doesn't grow as well when you disrupt the virus with mutations, then you know you've mutated or affected something that was important to the virus," says Ron Swanstrom, professor of microbiology and immunology.

"We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host."

Deep inside

Dr David Robertson from the University of Manchester welcomed this "definitive analysis".

"What this may reveal is some of the proteins operating at a level below the structures, which may have all sorts of functions within the virus.

"More generally, if we can unpick the structures then we can compare the systems of different viruses and gain new understanding of how they work."

Keith Alcorn of the HIV information service NAM added: "Encouraging the virus to mutate is not a new idea, but it is one of a number of options on the table.

"How important this information will be for the development of new drugs remains to be seen, but it is a useful addition to what we know."

http://news.bbc.co.uk/1/hi/health/8186263.stm