Tuesday, January 31, 2012

Scientists Create Map For Doomsday Pathway In Cells

Scientists Create Map For Doomsday Pathway In Cells

JANUARY 31, 2012

In the latest issue of the journal Cell, Chinese researchers unravel important steps of the necrosis pathway previously unknown to researchers.

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AsianScientist (Jan. 31, 2012) – In the latest issue of the journal Cell, a research team led by Xiaodong Wang of the National Institute of Biological Sciences (NIBS) has unraveled important steps of a cell death pathway previously unknown to researchers.

Cell death – responsible for the separation of our finger digits from a webbed state and other life processes – can only be executed with complicated and tight regulation. Cells destined for death that escape their “doomsday” fate become immortalized, leading to unwanted consequences such as tumor formation and cancer.

Two major forms of programmed cell death exist: apoptosis and necrosis. In apoptosis, the pathway involving proteins of the caspase family is well-characterized; in necrosis, however, many components of the pathway remain unclear.

In the first paper, lead author Sun and colleagues performed a screen that led to the discovery a small molecule inhibitor, necrosulfonamide, which could inhibit necrosis from taking place. The chemical did not block the interaction between receptor-interacting serine-threonine kinase 3 (RIP3) and RIP1, which forms a complex called the necrosome, but instead inhibited one or more unknown downstream steps.

By using mass spectrometry and other biochemical techniques, the team discovered that the inhibitor interacted with a protein called mixed lineage kinase-domain like protein (MLKL). Treating cells with necrosulfonamide or knocking down MLKL expression arrested necrosis at a specific step at which RIP3 formed discrete punctae in cells, suggesting that MLKL is an important adaptor protein in transducing signals from RIP3 to its downstream targets.

In the second paper, lead author Wang and colleagues discovered that a mitochondrial protein phosphatase PGAM5 acted as an antenna, converging multiple necrosis pathways into one.

Knocking down either splice variant of PGAM5 – PGAM5L (long form) or PGAM5S (short form) – attenuated necrosis caused by various signals, whereas knocking down RIP3 and MLKL blocked only TNF-α-mediated necrosis.

By piecing together the biochemical pathways of necrosis, these two studies not only contribute to an understanding of the downstream steps of necrosis, but also challenge conventional notion that necrosis is an unregulated and haphazard way for a cell to die.

The articles can be found at:


Copyright: Asian Scientist Magazine.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Thursday, January 26, 2012

Solutions for the most common migraine

What are the most common migraine triggers? (Conditions A-Z) - YouTube: ""

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UK could become 'smuggling hub' for herbal high khat BBC News -

A man chewing khatKhat is mainly used by older men in the Somali community but there are fears its use is spreading

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The UK could become a hub for smuggling the herbal stimulant khat, European police and politicians have warned.

The Netherlands is the latest country to outlaw the sale of the plant, which is now banned in sixteen EU member states and Norway.

Khat is freely sold in the UK and observers say the UK's isolated stance could make it the main base for Europe's khat trade.

The British government has commissioned a new review of khat use.

Until announcing its ban earlier this month, the Netherlands was similar in its stance to the UK where the East African plant is legally imported, sold and consumed.

In 2005 the UK Home Office commissioned a report by the Advisory Council on the Misuse of Drugs (ACMD) which concluded that "the evidence of harm resulting from khat use is not sufficient to recommend its control."

In the UK, the drug is mainly consumed by people of Somali and Yemeni origin and the ACMD report concluded there was "no evidence of its spread to the general population."

'Social harm'

Gerd Leers, Immigration and Integration Minister in the Netherlands, says he already has enough evidence of social harm caused by the drug to support a ban, which will come into force from June this year.

Start Quote

Muna Hassan

Those who argue against a ban don't know about the community and they can't see all the damage it is doing to families and individuals”

Muna HassanSister of khat user

Mark Lancaster, MP for Milton Keynes North, argued that khat should be outlawed in Britain in a speech he made in Parliament earlier this month.

But others say that making khat a controlled drug could lead to further problems.

"What worries me about the Netherlands is that once these legal Somali traders are criminalised and have their livelihood taken away from them - what are they going to do next?" says Axel Klein, an expert witness for the ACMD's 2005 report.

"They have contacts, trading skills, financial acumen so it is very possible that they will start trafficking the khat and then diversify into harder drugs.

"This is our main concern when looking at the UK as well.

"Do we really want to create the opportunity for an organised crime syndicate to start-up from nowhere with long term consequences by banning khat?"

Find out more

Hear more on The Report on Radio 4 on Thursday, 26 January at 20:00 GMT. You can listen again on the Radio 4 website or by downloading the podcast

Mr Klein argues that khat is chewed mainly by older men in the Somali diaspora and the practice will die out - rather like snuff has done in the UK.

But British-Somali Muna Hassan is not so sure. She blames khat use for inducing her younger brother's paranoid schizophrenia.

He has lived in the UK since the age of five and had a bright future ahead of him, studying at university, when he then started chewing khat.

"The Somali community has a unified voice on this," she told Radio 4'sThe Report.

"Those who argue against a ban don't know about the community and they can't see all the damage it is doing to families and individuals. We know," she says.

'Dangerous' drug

Eleni Palazidou, a psychiatrist who has worked with the Somali community in east London, agrees.

"For me it is a drug - no two ways about it.

"Every patient that I have seen who chews khat, I have seen them worsening and it is impossible to get their condition under control.

What is khat?

Box of khat
  • Khat refers to the leaves and shoots of the Catha edulis - a flowering shrub native to the Horn of Africa and Arabian peninsula
  • Khat has many names including 'qat' (Yemen), 'jad' or 'chad' (Ethiopia, Somalia), 'miraa' (Kenya) or 'marungi' (Uganda, Rwanda).
  • Khat leaves are chewed and contain stimulant substances that have amphetamine-like properties.
  • Khat contains cathine and cathinone which, as isolated substances, are banned in the UK, but in khat leaves are not.
  • It is chewed mainly by men in khat houses known as Mafrishes, though there is anecdotal evidence of growing use by teenagers and women.
  • In the UK it is an informal, legal trade so it is impossible to know exactly how much is imported. Estimates range from 10 to 60 tonnes a week.

"What khat does to the brain is similar to amphetamines. I think heavy, regular use is dangerous.

I have no doubt that khat has a major adverse effect on people's mental health and does cause psychological problems," she told The Report.

The Netherlands' ban has been welcomed by Dutch citizens like Dagmar Oudshoorn, mayor of the village of Uithoorn, near Schipol, who says the khat trade has been a blight on her community.

"Four times a week 200 cars arrive with people who want to buy khat and they fight - we had stabbing incidents - and they leave rubbish everywhere.

"We want to refurbish our business area but because of the bad environment we lose investors and customers," she told the BBC.

Neighbouring states, where the drug has long been illegal, have also put pressure on the Dutch government in The Hague because they have seen a sharp increase in khat trafficking from Holland.

For Europe's Nordic countries, much of the khat arrives by truck across the Oresund bridge between Denmark and southern Sweden.

Swedish police estimate that 200 tonnes is smuggled into the country each year, with a street value of 150 euros (£125/$190) a kilo.

Start Quote

With the Eurotunnel you can get from London to Malmo in 15 hours. Britain will become the new hub in Europe that is for certain”

Detective Stefan KalmanSwedish police

After years of lobbying, Swedish MEP Olle Schmidt admits he was pleasantly surprised by the Dutch move to ban khat.

"There is a shift in the Netherlands. They no longer want to be seen as a liberal country where tourists can come to smoke pot and buy drugs.

"Now, of course, khat will come more extensively to the London airports and then be smuggled to the rest of Europe, because you can earn a lot of money with this drug," warns Mr Schmidt.

Stefan Kalman, a senior detective in the Swedish drug squad, says customs officers catch smugglers on the border several times a week.

"The couriers often have accidents because they drive so fast", he says.

"Sometimes they shoot past the border controls without stopping because they are nervous - khat is quite bulky and you cannot conceal it like other drugs."

They are also in a rush because the drug has to be consumed when it is fresh.

Cathinone, one of the psychoactive agents in khat leaves, is highly unstable and loses its potency within three days of harvesting.

With the door slammed shut in Holland, smugglers will turn to the UK despite the longer distances says Detective Kalman.

"With the Eurotunnel you can get from London to Malmo in 15 hours. Britain will become the new hub in Europe that is for certain."

The British government has commissioned a new review of khat use - the date of its publication is still to be confirmed.

The Report is one BBC Radio 4 Thursday, 26 January at 20:00 GMT. Listen via the Radio 4 website or download the programme podcast.