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

Fewer chances of getting a job

The average number of graduates chasing every job on offer this year has risen to 48 and graduate starting salaries have been frozen, a report says.

There were 25% fewer jobs available in the UK on the last recruitment round, the Association of Graduate Recruiters said after surveying 226 members.

A report on BBC News basically says us graduates are highly unlikely to get a job - there are fewer jobs, more graduates, more competition and if we do get a job it will not be very well payed since salary rises are being frozen.

You'd think that someone with my varied skillset would see jobs all over the place but it's not true. There are fewer jobs and I "can't do" a lot of the jobs advertised. The problem is that those job advertisers seek a couple of things that I, on the face of it, can't give - experience (e.g. 2+ years), certain skills in Biology like basic genetic analysis which which we were never taught in Medical Sciences (!), skills/languages in IT like C#.NET, MSSQL and Oracle. How am I meant to get these skills if I've never done them?

I'm pretty sure I can learn all of these and very fast if I was given the chance but they never do give you a chance. There's always someone out there who has tried these things that you lack but may not be as good as you but they will get the job anyway. And in order to have experience in a work environment I need a job in the field to get such experience - personal experience is not good enough for them. Catch 22. It's depressing.

Microhomology-mediated End Joining

So I wrote a new article on Wikipedia. It's a little brief but with some collaboration from other internet users it will get better in time.

Microhomology-mediated End Joining

Microhomology-mediated End Joining (MMEJ) is one of the pathways for repairing double-strand breaks in DNA. Two other well known means of double-strand breakage repair are Non-homologous end joining (NHEJ) and Homologous recombination (HR). What distinguishes MMEJ from the other repair mechanisms is the use of 5 - 25 base pair microhomologous sequences to align the broken strands before joining, MMEJ repair is different to NHEJ because it uses a Ku protein and DNA-PK independent repair mechanism and repair occurs during the S phase of the cell cycle as a pose to the G0/G1 and early S phases in NHEJ and late S to G2 phase in HR.

MMEJ works by ligating the mismatched hanging strands of DNA, removing overhanging nucleotides and filling in the missing base pairs. When a break occurs a homology of 5 - 25 complimentary base pairs on both strands is identified and used as a basis for which to align the strands with mismatched ends. Once aligned, any overhanging bases (flaps) and mismatched bases on the strands are removed and any missing nucleotides are inserted. As this method's only way of identifying if the two strands are related is based on microhomology down/up-stream from the site of breakage, it does not identify any missing base pairs which may have been lost during the break and even removes nucleotides (flaps) in order to ligate the strand. MMEJ ligates the DNA strands without checking for consistency and causes deletions since it removes base pairs (flaps) on the strand in order to align the two pieces.

MMEJ is an error-prone method of repair and results in deletion mutations in the genetic code which may initiate the creation of oncogenes that could lead to the development of cancer. In most cases a cell uses MMEJ only when the NHEJ method is unavailable or unsuitable due to the disadvantage posed by introducing deletions into the genetic code.

References

1. http://www.cell.com/trends/genetics/abstract/S0168-9525(08)00229-1 MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings
2. http://nar.oxfordjournals.org/cgi/content/abstract/32/17/5249 DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining
3. http://dx.doi.org/10.1016/j.mrfmmm.2007.08.016 Distinctive differences in DNA double-strand break repair between normal urothelial and urothelial carcinoma cells

Green-Glowing Marmoset Monkeys

Genetically modified primates that glow green and pass the trait on to their offspring could aid the fight against human disease.

Though primates that make a glowing protein have been created before, these are the first to keep the change in their bloodlines.

Future modifications could lead to treatments for a range of diseases.

The "transgenic" marmosets, created by a Japanese team, have been described in the journal Nature.

The work raises a number of ethical questions about deliberately exposing a bloodline of animals to such diseases.

Scientists have managed to modify the genes of many living organisms in recent years, ranging from bacteria to mice.

Mice have been particularly useful experimental models for studying a wide range of human diseases as modified genes are passed on from parents to progeny.

However, mice are not useful for some human diseases because they are not sufficiently similar to produce effects that are meaningful to human disease. Studies of mice with Alzheimer's disease, for example, were stymied simply because their brains were too small to scan at sufficient resolution.

Jellyfish gene

Now, Erika Sasaki of the Central Institute for Experimental Animals in Japan, and her colleagues, have introduced a gene into marmoset embryos that allows them to build green fluorescent protein (GFP) in their tissues.

The protein is so-called because it glows green in a process known as fluorescence.

GFP was originally isolated from the jellyfish Aequorea victoria, which glows green when exposed to blue light.

The protein has become a standard in biology and genetic engineering, and its discovery even warranted a Nobel prize.

Glowing mice have already been created in the lab 'Glowing' jellyfish grabs Nobel

From 91 embryos, a total of five GFP-enabled transgenic marmosets were born, including twins Kei and Kou ("keikou" is Japanese for "fluorescence").

Crucially, the team was able to show that their method is maintained in the family - or germline.

They used the sperm from a member of the first generation of transgenic marmosets to fertilise an egg from a normal animal. A significant proportion of the resulting offspring also glowed under ultraviolet light.

Until now, efforts to establish transgenic lines of primates have been unsuccessful. In 2001, a team at the Oregon Regional Primate Research Center, US, succeeded in creating a rhesus macaque that expressed GFP.

Last year, a team at Yerkes National Primate Research Center, Atlanta, US, created rhesus macaque monkeys with Huntington's disease. Four of those are still awaiting puberty, and the researchers hope that they will produce a second generation of macaques with the disease.

Fitting in

The new method improves on previous work using so-called "retroviruses".

These virus "vectors" were added to a soup of sugary solution and this was in turn injected into the monkey embryos.

Although the work demonstrates the principle that a gene can be introduced into a primate bloodline, study co-author Hideyuki Okano of the Keio University School of Medicine said it may not be suitable for studying all diseases.

"We can just introduce genes by virus vectors," he told BBC News, "so the limitation comes from the sizes of genes that can be carried by the retroviruses."

That limitation is about 10,000 bases, or letters, of the genetic code. That upper bound will constrain the diseases that can be studied.

Genes implicated in Parkinson's disease and amyotrophic lateral sclerosis (ALS, a form of motor neurone disease) may well be suitable.

However, genetic regions implicated in Huntington's disease might not fit into a retrovirus.

Two of the first transgenic marmosets did their own genetic trick: they are twins

The work has raised a number of ethical questions about the use of primates in disease research.

Marmosets are New World monkeys and therefore more distantly related to humans than, for example, chimpanzees. But they are particularly useful for the study of disease because they reproduce often and from a young age.

Jarrod Bailey, science consultant to the British Union for the Abolition of Vivisection (BUAV), says he is "disappointed" both ethically and scientifically with the results.

"This sort of research on animals as sentient as monkeys and apes does not have public support," he told BBC News.

Furthermore, he thinks the underlying science is flawed. Animal researchers, he said, "have failed in research to find treatments for Aids, for hepatitis, for malaria, for strokes. Many treatments for strokes work in monkeys but don't work in humans."

"Monkeys do not predict human response and do not tell us about human disease," he added.

However, scientists argue that, because primates are more similar to humans than mice, they present a more refined model of human disease. This would allow scientists to test treatments more effectively, meaning that fewer animals need be experimented on in the long run.

"This experiment is reminiscent of the exciting early days of transgenic research where it was initially difficult to fully know what the potential applications and future research directions might be," said Mark Hill, a cell biologist at the University of New South Wales in Australia.

"As always in this area of research, there needs to be a close linkage between the scientific work, ethical issues and regulatory guidelines."

http://news.bbc.co.uk/1/hi/sci/tech/8070252.stm

Sequencing of Mouse Genome completed

Scientists have finished sequencing the mouse genome after a 10-year effort.

The humble mouse is the experimental workhorse in laboratories worldwide, so this high-quality genome sequence will aid in the fight against human disease.

The search for novel treatments could benefit from a greater understanding of the mouse genetic code, which is about 75% similar to our own.

An international team of researchers have published details of the work in the open-access journal PLoS Biology.

The sequence comprises the full complement of genetic material in the nucleus of a cell. It is effectively the genetic "instruction booklet" for a living animal.

The mouse (Mus musculus) becomes only the second mammal after humans to have its complete genome laid bare.

But draft sequences have been published for the chimp, dog, rat, cat, macaque and even the duck-billed platypus

The mouse is the animal most often used to better understand human illnesses and how they develop.

Research carried out using mice has led to advances in the treatment of cancer, diabetes, heart disease and countless other conditions.

Good model

Co-author Professor Chris Ponting, from the University of Oxford, told BBC News the work confirmed that the mouse was an excellent experimental model for human disease.

"Completion of the genome is extremely important in helping us to identify the genes that underpin biology that is the same across all mammals," he said.

But he said it was also important to separate the genes humans shared with mice from those which differed between them.

About 75% of mouse genes have a single equivalent in humans. But some 5,000 genes arose after the ancestors of mice and humans went their separate evolutionary ways.

"In retrospect, our previous picture of the mouse genome was incomplete," said Dr Leo Goodstadt from the University of Oxford.

"Only when all the missing pieces of the genomic puzzle had been filled in did we realise that we had been missing large numbers of genes found only in mice, and not in humans."

The mouse genome sequencing effort began in 1999, and a draft sequence was published in 2002.

The cost, borne by US and UK sequencing centres, is estimated to exceed $100m (£62m).

Some groups oppose animal experimentation, campaigning to ban or limit the animals used.

In the UK, growth in the use of genetically modified (GM) animals - mainly mice - is largely responsible for a steady rise in the numbers of animals used in experiments since 1997.

Professor Ponting, from the Medical Research Council's (MRC) Functional Genomics Unit at Oxford, said the complete genome could provide insights into the evolution of mammals.

Humans and mice share a remarkable level of similarity, despite having evolved independently for the last 90 million years.

http://news.bbc.co.uk/1/hi/sci/tech/8069235.stm