A semen protein that helps HIV

An atomic-level look at an HIV accomplice:
[Via Eureka! Science News - Popular science news]

Since the discovery in 2007 that a component of human semen called SEVI boosts infectivity of the virus that causes AIDS, researchers have been trying to learn more about SEVI and how it works, in hopes of thwarting its infection-promoting activity.

[More]

Getting some structural understanding of how this peptide helps HIV enter a cell provides some greater understanding of the opportunistic aspects of the virus.

SEVI stands for semen-derived enhancer of virus infection and was found when researchers looks for inhibitors and enhancers of HIV in human semen. While it costs $30 to read the whole paper, the abstract provides a lot of info, including a picture of the protein SEVI is derived from.

Perhaps one of these inhibitors of HIV entry found in the blood will be useful. VIRIP could be very interesting. The gp41 protein of HIV is involved in the actions of both VIRIP and SEVI.

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Why football is like healthcare

Patriots by Brian J. McDermott
Fourth Down
[Via The Frontal Cortex]

Bill Belichick has never been the most popular coach in the NFL, but his Sunday night decision to go for it on 4th and 2 on his own 28 with two minutes remaining in the fourth quarter has even his fans crying foul. I bring up this football decision not because I’m interested in a debate – as a Pats fan, the last five minutes of that game were excruciating – but because I think it illustrates the difficulty of making rational decisions, even when the evidence supports the call.

I’ve blogged about the research of UC Berkeley economist David Romer before, but his basic thesis, based on an exhaustive statistical analysis of 4th down scenarios, is that NFL coaches are irrationally risk-averse. They punt the ball way too frequently and kick far too many field goals.

Belichick was an econ major, and has expressed a familiarity with Romer’s research. Nicholas Beaudrot has persuasively shown how, from this econometric perspective, Belichick’s bizarre decision actually makes perfect sense:

On 4th down, with 2 yards or fewer to go, New England has gained a first down on approximately 66% of its attempts with Tom Brady as quarterback. The Colts had one timeout. If the Patriots gain a first down, the game ends; they can slowly walk to burn a few seconds, then take a knee on each down to end the game. If they don’t gain a first down, the Colts would still need to score a touchdown to win the game. Let’s give the Colts a probability P of getting the six if the ball starts at the 28 yard line. So if the Patriots try for the first, their chance of losing is

(Probability of 4th down failure) x
(Probability of Colts scoring a TD from the 28 Yard line) = 0.33P

The average New England punt nets about 40 yards. Let’s give the Colts a probability Q of scoring a TD on a driving starting at the Indianapolis 32. Then, the chance of the Patriots losing is simply Q. For Belichick’s decision to make sense, we just have to believe that he gave his team a lower chance of losing. In math terms, that would mean 0.33P < Q. Doing some algebra leaves you with P < 3Q. In other words, for the Patriots to have made the right decision, we only have to believe the Colts odds of scoring a TD on a drive starting 28 yards from the end zone are less than three times the odds of the same outcome starting from 68 yards out. The win probability graph for the game suggests that, given 1st-and-10 from New England’s 29, the Colts had roughly a 51% chance of winning in the actual situation. We have to believe that their chances under the punt scenario were above 17% for Belichick to have made a bad good decision. Considering the Colts’ have scored touchdowns on 30% of their offensive possessions, my guess is that this was a good one.

The reason I bring up this analysis is to demonstrate that even defensible decisions can have wrenching emotional consequences. Belichick’s call might have been statistically correct, but it felt horribly wrong.

And this kind of contradiction isn’t just relevant for football coaches. Just consider health care: the only way we’re ever going to reduce medical costs is to restrict procedures that haven’t passed evidence-based efficacy tests. Maybe that means 40 year old women don’t get mammograms, or that we treat prostrate cancer less aggressively, or that we stop performing spinal fusion surgeries. Although there’s solid evidence to question all of these medical options, such changes provoke intense debate. Why? Because our emotions don’t understand statistics. Because when we have back pain we want an MRI. Because when it’s our father with prostate cancer we want the most aggressive possible treatments. And so on.

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All the numbers in the world prove Belichick made the right call. But they ignore some basic human frailties. Often the pain of failure far outweighs the joy of success. This is as true for football as it is for human health.

People are willing to seek out very hazardous therapies for even a slight increase in their chance of survival.

A very large percentage of women will undergo chemotherapy for cancer, even if it only provides a 1% survival advantage. And those women with direct experience with chemotherapy were even more likely to accept it.

Now this is interesting because the mortality rate due to the chemotherapy itself is between 0.5% and 1.5%. So the women were willing to undergo a therapy that had about a 1% chance of directly killing them within 30 days in order to gain a 1% chance of living. That does not seem like a very rational decision.

Rational discussion and statistics are much easier to do when they are general and not personal. Like with the Patriots. If you are not a fan, it is easy to look at the numbers and say, ‘Hell, yeah. Go for it.’

But it you were a Patriots fan, you wanted them to punt. The Colts might have really good odds scoring from 68 yards. It could still turn out that in this game, on that day, they failed. That is why people want the Pats to punt.

It is why people gamble at all. The odds are always against them but only in the long run. Individuals hope that for just this one time, this one moment, the odds favor them.

When it is your life, feelings get much stronger, since losing ends any chance of ever trying any therapy ever again.

Doing the right thing statistically does not reduce the pain of losing. It may be right that 95% of the time, nothing needs to be done. But if you happen to be in that 5%, you sure wish something was done. Finding the right balancing act between social benefits and individual needs is going to be tough over the next few years.

This is where head intelligence meets gut intelligence. While the former is correct far more often, the latter is often just too powerful to ignore. It usually takes a lot of training and rigor to see that ‘common wisdom’ is simply wrong and that the gut is providing incorrect information.

[Listening to: Mog Ruith from the album "The Inconsolable Secret" by Glass Hammer]
[Listening to: Thick As A Brick (Part 2) from the album "Thick As A Brick" by Jethro Tull]

Keep on screening

livestrong by KaCey97007

Rethinking cancer screening?
[Via Respectful Insolence ]

ResearchBlogging.orgHere we go again.

I see that the kerfuffle over screening for cancer has erupted again to the point where it’s found its way out of the rarified air of specialty journals to general medical journals and hence into the mainstream press. This is something that seems to pop up every so often, much to the consternation of lay people and primary care doctors alike, often trumpeted with breathless headlines along the lines of “What if everything you knew about screening was wrong?

It isn’t, but some of it may be. The problem is the shaking out process. I’ll try to explain.

Over the last couple of weeks, articles have appeared in newspapers such as the New York Times and Chicago Tribune, radio networks like NPR, and magazines such as TIME Magazine pointing out that a “rethinking” of routine screening for breast and prostate cancer is under way. The articles bear titles such as A Rethink On Prostate and Breast Cancer Screening, Cancer Society, in Shift, Has Concerns on Screenings, Cancers Can Vanish Without Treatment, but How?, Seniors face conflicting advice on cancer tests: Benefit-risk questions lead some to call for age cutoffs, and Rethinking the benefits of breast and prostate cancer screening. These articles were inspired by an editorial published in JAMA last month by Laura Esserman, Yiwey Shieh, and Ian Thompson entitled, appropriately enough, Rethinking Screening for Breast Cancer and Prostate Cancer. The article was a review and analysis of recent studies about the benefits of screening for breast and prostate cancer in asymptomatic populations and concluded that the benefits of large scale screening programs for breast cancer and prostate cancer tend to be oversold and that they come at a higher price than is usually acknowledged.

Read the rest of this post… | Read the comments on this post…

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It is easy to read the headlines and think that screening does not work. It does but we also need to recognize that just doing more screening does not necessarily help if we do not really understand all the facets underlying the disease being screened for.
It turns out that a significant minority of breast cancers resolve on their own. We really do not have a good way of knowing which ones have to be treated now and which would resolve without treatment. Some cancers might be very slow growing and present a very small chance of mortality. But, again, we can not really tell the difference, so all get treated the same.
As the blog post states:

So what’s the solution? Should we give up on screening?

I’ll answer the second question with an emphatic absolutely not. There is no doubt that screening can save lives; the problem is that we’re doing it “bigger” and “badder” and not necessarily better or smarter, using more or less a one-size-fits-all approach when a more tailored approach might actually be necessary. Also, we’re using 20th century technology, when 21st century technology might be able to find a way out of these conundrums. Here’s where I (mostly) agree with Esserman et al. We need to change how we screen for common cancers using the latest advances in biochemistry, molecular biology, and technology to differentiate which lesions are most likely to be cancer and which are not, which cancers are likely to progress to the point of threatening a patient’s life in their remaining lifespan and which ones are not.

We need to improve our screening approaches by having a better understanding of all the biology involved, including the specific biology that an individual possesses. We will get there but it may be a little confusing until then.

Producing swine flu vaccine

chicken eggs by themissiah

Barbara Ehrenreich on the swine flu supply problem

[Via Effect Measure]

I first read Barbara Ehrenreich in 1971 when she wrote The American Health Empire: Power, Profits, and Politics with her (then) husband John Ehrenreich (Health PAC, 1971). She was by then a PhD in cell biology (Rockefeller University) and anti-war activist. We traveled in the same circles and I knew her slightly at the time. Her next book, Witches, Midwives, and Nurses: A History of Women Healers (with Deirdre English) was a new reading of women in medical history. It was an influential text in the emerging women’s health movement. Since then she has published many books, several making the best seller lists and throughout an astute and still influential observer. Now she has penned a brief comment on the the alleged swine flu vaccine supply problem and who’s to blame. And I find myself in complete agreement with her:

[More]

There is a really nice discussion in the comments about many aspects of the shortage and the place for Pharma in vaccine production. The big problem with the delivery of so many doses is actually one that most Big Pharma could have answered honestly 6 months ago with a ‘gray’ answer, rather than the black and white one we all wanted.

First, the normal seasonal vaccine had to be made. This is already a massive enterprise, one that has resulted in shortages in years past when things got messed up in the process.

Second, an additional 120 million doses needed to be made and packaged using the H1N1 virus. While the process should have been just like normal seasonal flu, there was one problem, one that has popped up before and resulted in some shortages – the production of vaccine per egg was lower than normal So it required even more specially treated fertilized chicken eggs to produce the large number of doses than normal.

Most research personnel, when asked what they could produce, might have said 120 million, assuming things remain the same as usual. The assumption gets removed by the time upper management hears it and the government does not really want to hear the full answer. Everyone has an incentive to say “yeah. 120 million doses.”

Sometimes, yields are not as expected. This can usually be overcome by just using more eggs. But I would expect that there really were no more eggs available in the timeframe needed.

So, when things start heading south, people do what people do. Hope something fixes the problem. Make sure they are not the ones who get the blame. One way to do that would be to extend the effectiveness of the doses by using adjuvants or reduced doses.

And we have seen attempts at both of those. I think they really hoped that they could get an effective 120 million doses by using such measures. It was only in the last month of so that they realized that even these would not be effective.

As often happens in human endeavors, hope was the plan.

One big problem is that market forces for vaccine development are not always useful for producing the best vaccine for the public. Millions of cheap doses are not something that is attractive to many companies. And they have little incentive to develop new and better technologies which can cost billions and take a long time for their costs to be recouped.

Thus we are still using 50 year old, or more, technology for almost all of our vaccines. This needs to change.

Because someday, an avian flu virus will produce a pandemic. And little vaccine will be able to be produced.

Avian flu kills birds. Chicken eggs are from birds. Trying to produce flu vaccine in chicken eggs using avian flu results in very, very (if any) vaccine. Luckily, the current pandemic flu permits some vaccine to be produced, even at lower levels.

If it was avian flu, we might not be able to produce any vaccine in chicken eggs at all.

We need some of the better approaches that are wending their way through approval.

[Listening to: Skateaway from the album "Private Investigations - The Best Of" by Dire Straits]

Buy stock in hard drive companies

What’s in an Illumina GA run directory?:
[Via PolITiGenomics]

One of the main things that differentiates genomics from other endeavors that use a lot of disk space is that genomics file systems tend to have a lot of files (millions). This was true with Sanger sequencing, and it seems to be even more true with next-generation sequencing technologies, especially Illumina/Solexa and AB SOLiD. This large number of files and the parallel access of these files by large computational clusters tends to give most storage solutions great difficulty.So what, exactly, is in an Illumina run directory? Well, to get breakdowns of file statistics there is a nifty little tool called fsstats. It is just a simple Perl script that crawls through a directory stat’ing files and reporting metrics. For example, when you run it on an Illumina GA IIx 2×100, high cluster density run after the primary analysis has completed, you get the following information about the distribution of file sizes. (I have rearranged and condensed the information to make it fit.)

total 7.46 TB used to store 7.46 TB user data, overhead 0.04%
count=991227 avg=8076.50 KB
min=0.00 KB max=13128679.30 KB
size range    count   %tot  %tot cum       total size   %tot  %tot cum
[       0-       2 KB):   4019 ( 0.41) (  0.41)       3009.03 KB ( 0.00) (  0.00)
[       2-       4 KB):      2 ( 0.00) (  0.41)          6.99 KB ( 0.00) (  0.00)
[       4-       8 KB):    981 ( 0.10) (  0.50)       5964.82 KB ( 0.00) (  0.00)
[       8-      16 KB): 193351 (19.51) ( 20.01)    2588619.88 KB ( 0.03) (  0.03)
[      16-      32 KB):   2656 ( 0.27) ( 20.28)      58586.79 KB ( 0.00) (  0.03)
[      32-      64 KB):    901 ( 0.09) ( 20.37)      31369.79 KB ( 0.00) (  0.03)
[      64-     128 KB):   2893 ( 0.29) ( 20.66)     303872.38 KB ( 0.00) (  0.04)
[     128-     256 KB):      2 ( 0.00) ( 20.66)        345.34 KB ( 0.00) (  0.04)
[     256-     512 KB):      4 ( 0.00) ( 20.66)       1222.53 KB ( 0.00) (  0.04)
[     512-    1024 KB):      1 ( 0.00) ( 20.66)        622.26 KB ( 0.00) (  0.04)
[    1024-    2048 KB):      2 ( 0.00) ( 20.66)       3199.89 KB ( 0.00) (  0.04)
[    2048-    4096 KB):     12 ( 0.00) ( 20.66)      41779.69 KB ( 0.00) (  0.04)
[    4096-    8192 KB): 776654 (78.35) ( 99.02) 5863161178.18 KB (73.24) ( 73.28)
[   16384-   32768 KB):     21 ( 0.00) ( 99.02)     487156.46 KB ( 0.01) ( 73.28)
[   32768-   65536 KB):   3856 ( 0.39) ( 99.41)  163552521.17 KB ( 2.04) ( 75.32)
[   65536-  131072 KB):   3825 ( 0.39) ( 99.79)  307535341.32 KB ( 3.84) ( 79.17)
[  131072-  262144 KB):    133 ( 0.01) ( 99.81)   32458046.12 KB ( 0.41) ( 79.57)
[  262144-  524288 KB):   1787 ( 0.18) ( 99.99)  658830514.46 KB ( 8.23) ( 87.80)
[ 2097152- 4194304 KB):     16 ( 0.00) ( 99.99)   47898262.36 KB ( 0.60) ( 88.40)
[ 4194304- 8388608 KB):     64 ( 0.01) (100.00)  432084134.39 KB ( 5.40) ( 93.80)
[ 8388608-16777216 KB):     47 ( 0.00) (100.00)  496603147.67 KB ( 6.20) (100.00)

So the total size of the run directory is nearly 7.5 TB and there are almost one million files. The average size of a file in the run directory is about 8 MB and the maximum size is over 13 GB. The images (represented in the 4096-8192 KB range), comprise over 78% of the files and 73% of the total size of the run directory. This significant penalty can be avoided by using RTA and not transferring image files. The largest files are the alignment (ELAND) outputs and the FASTQ files in the GERALD directory. Speaking of directories, here is a breakdown by number of files in each directory.

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7.5 terabytes! One million files! That just boggles the imagination. I love how the sizes are still in kilobytes. 1 terabyte is over a million kilobytes. or 1000 gigabytes. A blue ray disk can store up to 50 gigabytes on a dual layer disk so 1 terabyte would take 20 of these disks.

With all the sequencing going on, there will be lots of huge storage centers to hold all the data. I wonder how long it takes to back up several terabytes of information?

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Flu vaccination for all is the cure

spanish flu by stevechasmar

NIAID scientists propose new explanation for flu virus antigenic drift

[Via EurekAlert! - Infectious and Emerging Diseases]

(NIH/National Institute of Allergy and Infectious Diseases) Influenza viruses evade infection-fighting antibodies by constantly changing the shape of their major surface protein. Now, researchers from NIH/National Institute of Allergy and Infectious Diseases have proposed a new explanation for the evolutionary forces that drive antigenic drift.

[More]

Pretty cool little experiment here. Using a mouse model, they showed that the response of the flu virus to people already immunized against it was to increase the binding of one of its coat proteins to a receptor found on human cells. By doing this, it shielded this protein from the very antibodies that had been developed to neutralize the virus.

Evolution in action.

But if the virus produced mutants that bound too tightly, it was rendered less infective. The virus gets stuck to cells in the nose and never makes it to the lungs. Wonderful

What was really interesting was that when these mutated viruses were put into naive mice that had no antibodies to the virus, the virus tended to revert back to normal binding activity and the virus bound the receptor with a low affinity.

It usually did this by making new mutations in other areas of the protein involved in binding to cells. But because the viruses retained the original mutations, they still retained a greater ability to evade antibodies than the original flu viruses.

From their paper:


200911050930.jpg  

The blue shows the cell binding ability in each round while the red represents the ability to evade detection by the immune system.

What they found was that each round of pressure-release generated sets of mutations that altered the affinity for the receptor and that also resulted in escape from antibody recognition. When pressure was released, new mutations occurred that reduced the receptor binding back to normal. But the ability of these new forms of the virus to escape detection from antibodies remained higher than before.

SInce each round tended to result in different mutations, the cumulative effects after several rounds were to have a virus which was substantially able to escape antibody detection, even in immunized humans. eventually enough mutations would accumulate for the virus to completely evade the immune system, even in vaccinated humans.

The authors postulate that this is a major cause for antigenic drift, the small changes that are seen in the flu virus from season to season. Moving from selective pressure in vaccinated humans to unselected naive humans and back again creates a push me-pull you effect, driving rapid change in the virus.

This drift would be what causes new forms of flu to be seen each year. This process increases the chances that new mutations will occur that escape antibody detection, resulting in a new seasonal flu outbreak.

Putting organisms under selective pressure, then removing that pressure, then reapplying it has been shown to drive very rapid genetic changes. This often results in mutants that can elude the selective pressure. This is often why antibiotics fail when they are not used properly. It is the iterative process of pressure, release, pressure, release that can often create mutants that evade whatever the selective pressure is, such as our immune system.

The key to preventing this would then be to come up with a way to prevent the release of the selective pressure being applied by the immune system. The pressure needs to constantly be applied.

The authors suggest that increasing herd immunity by increasing the vaccination of the major pools for the virus, such as children, will provide the virus with fewer places to revert and mutate. This would keep the pressure up enough to prevent the sorts of antigenic shift that we see.

The virus would then be under continuing pressure to stick really strongly to the receptor and maybe never make it to the lungs at all. At least this would greatly reduce the ability for antigenic drift to occur, reducing the need to come up with new seasonal vaccines each year.

It is a nice hypothesis. It implies that greater vaccination would reduce the drift we see each year, making it less likely that the seasonal outbreaks would keep occurring. Thus we would only have to get one (or a few) vaccinations in our lifetimes. Until an antigenic shift occurred and we needed a new vaccine.

Failing in science

The Hidden Economic Carnage in Science and Education

[Via The Scholarly Kitchen]

Economic statistics don’t measure science or training well. Our fields are being hurt inordinately, but the damage isn’t being measured. What will it mean long-term?

[More]

Anyone who thinks things are getting better needs to read this. Because it is often the best trained, most intelligent ones who are being forced to leave. We are beginning to provide much fewer rationales for people to spend so much time becoming well trained and very educated.

Especially if those people are let go because their expertise costs too much money. We already treat airline pilots as bus drivers with some working at regional carriers making $22,000 a year, the poverty line for a family of four.

Because our current system does do really want to pay for expertise.

I love the last paragraphs:

So, the next time you hear that perhaps the recession is lifting, that halcyon days are on the horizon, remember that the numbers being used for those rosy projections are based on items that are easy to measure, slower to grow, of decreasing value, and not vital for future growth.

This could be a lesson in how intangibles become tangible, I’m afraid.

It will be a long time before employment levels are back up to what they were, especially for those with the most training.

Quality AND quantity

texture by dog ma

The Sea Change That’s Challenging Biology’s Central Dogma

[Via Discover Magazine | RSS]

For decades, RNA was seen as a simple slave to DNA. Newer research shows it has an active and critical role in every disease from Alzheimer’s to cancer.

[More]

This is a great story about how a small group of focussed people working on a seemingly obscure problem can sometimes provide incredible insight. The author provides some really great insight into the path the research took, including the fact that the researcher who first published on this work, who was one of the key instrumental scientists involved, did not initially get tenure.

His work was viewed as too obscure.

The article does an excellent job of portraying these researchers as flesh and blood humans, rather than Promethean geniuses or lone wolfs.

The only thing a little off is that this work’s challenge to the Central Dogma (i.e. DNA to RNA to Protein) is a little more subtle than simply overturning it. It is more like the effect of Relativity on Newtonian mechanics.

It provides a more sophisticated explanation while leaving much of the framework intact.

In the Central Dogma, proteins are the really important things. They determine just what a cell does. DNA is simply the memory and RNA the transmitter. But proteins are the key.

The big challenge this work provides, where it does some real overturning of paradigms, are to some of the hypotheses regarding so-called junk DNA. Many people have had a feeling that this supposedly unused DNA might actually have a use. It has just been hard to figure out what it is. Now we have an idea of what some of it does.

It is there for a reason.

And what it does is really important. One area where the Central Dogma is influential is with the idea of genomic sequencing as an insight into disease. ‘If we want to know what the protein sequence is, we can look at the DNA sequence.’

However, it is really hard to determine the sequence of a protein, while it is easy to get DNA sequences. So genomic sequencing has been a surrogate for having protein sequences. The Dogma suggests that there is a one-to-one mapping of DNA sequence and protein sequence. With some small exceptions, this remains true.

This makes sense since mutations in DNA often produce alterations in proteins. A change in quality of one is seen in a change in the quality of the other. So we have been hearing a lot about getting everyone’s DNA sequenced. Then we will know what diseases they are likely to be susceptible to. At least in a simple world.

This is a leftover of the Central Dogma’s proposal that changes in proteins are reflected in changes in DNA sequences. But I have already discussed how epigenetic factors (here, here, here, here, here ) can break this relationship, producing different disease states without changing the genetic sequences.

Proteins are still important. But simply knowing what their sequence is – indirectly from DNA – does not describe fully the complex nature of a cell. More than just protein sequence is used to determine what a cell does.

The work on microRNA demonstrates that simply knowing a person’s genomic sequences does not tell the whole story. These RNAs are critical for controlling the amount of different proteins found in each cell.

And the quantity may be just as important as the quality.

Along with epigenesis, microRNAs show us that disease can be caused by the wrong amount of a protein.

So, the dogma of DNA to RNA to Protein is still present. Things are just a little more complex. What a cell does is not just determined by the quality of protein, its sequence that then determines its structure and activity.

It is also determined by the quantity of the protein. Some cells may have a protein that can prevent disease. But if microRNAs prevent it from being produced, then we have disease. Knowing the DNA sequence might not really help us much in this case.

Having too much or too little of a particular protein in a specific cell may well be the cause for many of the diseases we see today. Sometimes it will be because the protein itself is ‘wrong’ and sometimes it will be because the amount of protein present is wrong.

Knowing the genomic sequence of a person will be really important and useful to have. But it will be critical to know how much protein is produced. Knowing how microRNAs work will be critical for understanding this.

[Listening to: Stuck On You from the album "Elv1s 30 #1 Hits" by Elvis Presley]

Bizarro world

fail road by fireflythegreat

Healthcare provision seeks to embrace prayer treatments

[Via LATimes]

I’m hoping this does not make it to the final bill. One of the big things that is being done for health care reform is to actually do some research to find out what procedures actually work and how well. It turns out that there has actually been little systematically done to examine this, at least compared to the multitude of just-so stories and personal anecdotes.

Having insurance companies pay for pseudo-scientific methods completely negates this approach and means that cost savings, by not doing things that really do not work, will be reduced.

And this opens up all sorts of abuses and unintended consequences.

We might possibly have something that pays for spiritual prayer healings but does not pay for legitimate medical procedures or practices.

Bad histones

200910261104.jpg from Wikipedia

Antibody ‘fixes internal bleeds’

[Via BBC News | Science/Nature | World Edition]

US scientists say they have discovered an antibody that could minimise the damage caused by major traumas.

[More]

Histones are necessary for proper packaging of the very long chromosomes in the very small nucleus. They are also important in controlling gene expression. But I have to point out an error in the report that makes me want to search out the real paper.

It regulates the DNA, causing it to fold and form the characteristic double helix.

Histones have nothing to do with DNA and the double helix. DNA forms that structure by itself. Histones deal with higher oder packing of the DNA as it wraps around the histones.

So let’s look at a couple of other reports, as this BBC one has lost ,y confidence that it is reporting accurately. ScienceDaily gives us the actual press release, which does provide some better information.

Histones released from dying cells damage the lining of blood vessels. this may be the cause of some of the major problems we see following various traumas – internal bleeding into the surrounding tissue.

In fact, this sort of damage is what drives things such as sepsis. Sepsis can kill very rapidly, often from the huge response the body makes to try and fix things.

Few things have been found to be very effective against sepsis once it gets going. It can kill very rapidly and most of the therapy is palliative in nature, keeping the patient alive long enough for their body to deal with the damage.

An antibody therapy would be pretty straightforward. Infusion with the antibody would soak of the histones and thee damage they do would be reduced.

If this actually helps in a meaningful way, it could be a real breakthrough. Let’s just see what happens in humans.

To me, the really amazing fact is that histones do so much damage. I wonder just what the mechanism is. I’m waiting for this to turn up on CSI – the victim was injected with large histones which mimicked sepsis, resulting in the death of the victim.

Parasites for Halloween

This Month’s Sci-Fi Worthy Parasite: Taenia solium:
[Via Observations of a Nerd]

It’s that time of the year again… the temperature is dropping, pumpkins are being carved, and there’s that creepy rustling in the woods as you walk by. All Hallow’s Eve fast approaches, and with it come tales of mysterious disappearances, strange sightings, and all kinds of things that go bump in the night.

So what better parasite to talk about than one that is sure to give you the heebie-jeebies? It’s a parasite that you could have for years and not even know it, until one day you’re in the hospital with seizures, headaches, nausea, vomiting, or even altered mental status.

Of course, I’m talking about Taenia solium, better known as the Pork Tapeworm.

[More]

Parasites are always nasty to think about. Probably way the chest-pursting phase of Alien is the hardest part to watch.

But the pork tapeworm is especially nasty, not only for what it does to our bodies but what our bodies can eventually do to ourselves. I had always been told to make sure the pork is fully cooked but now I know why.

Nice to know that freezing the meat for 5 days will also kill the parasite.

It is enough to make you go off of the other white meat.

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A new way to see

Image of individual red blood cells lined up within a single capillary in a mouse's ear.

A team of Harvard chemists led by X. Sunney Xie has developed a new microscopic technique for seeing, in color, molecules with undetectable fluorescence. The room-temperature technique allows researchers to identify previously unseen molecules in living organisms and offers broad applications in biomedical imaging and research.

The scientists’ results are published in the Oct. 22 issue of Nature. Partial funding for the project was provided by the National Science …

More at http://www.nsf.gov/news/news_summ.jsp?cntn_id=115817&WT.mc_id=USNSF_51

This is an NSF News item.

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I always love new methods for visualizing biological systems. This holds the promise to see molecules in living tissue that we have previously been unable to see. New technologies allow us to answer questions unthought up before.

The results of this could be quite exciting (pun intended).

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More epigenetics. This time with autism.

Study reveals possible link between autism and oxytocin gene via non-DNA sequence mutation:
[Via Eureka! Science News - Popular science news]

A new study indicates a link between autism and alterations to the oxytocin receptor, OXTR, caused by inherited alterations that do not involve DNA sequence mutation. The study, published in the open access journal BMC Medicine, identified the non-DNA change in ‘OXTR’ via an autistic child and his mother, who potentially has obsessive-compulsive disorder.

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This is a very preliminary paper. Remember, correlation does not mean causation. They make the point that autism is caused by many things.

What is interesting is that the oxycontin receptor gene is altered, not in its sequence by in an epigenetic process called CpG methylation of the DNA. They show that in cells from the peripheral blood and temporal cortex of autism patients there is an increased pattern of methylation of the areas that control expression of the oxycontin receptor.

DNA methylation usually acts to reduce gene expression. That is exactly what they saw in these patients for the oxycontin receptor gene.

Some more work will need to be done to prove any sort of causation. But this is an instance where simply having the genomic DNA sequence would not be very helpful because current techniques do not differentiate between regular DNA and methylated DNA.

So all these sequences would have looked normal because there were not any sequence mutations. It may very well be necessary to determine methylation patterns in addition to sequence in order to get a better idea of what is really going on.

Either that or directly sequence the mRNAs and try to get a real feeling for how much gene expression patterns are altered.

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Copper bracelets and arthritis

Copper bracelets and arthritis

[Via Health News from NHS Choices]

“Copper bracelets and magnetic wrist straps are useless for relieving pain in people with arthritis,” BBC News has reported. It said that the first tightly controlled study of the interventions found no benefit in treating pain or stiffness from the condition.

This report is based on a robust study design and shows good evidence that magnetic wrist straps and copper bracelets have little or no effect on pain, physical function, stiffness or medication use in people with osteoarthritis.

According to this study, any benefit these devices may have, which the BBC reports can costs between £25 and £65, may be explained by the placebo effect.

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I’m really getting to like this site. It does a great job explaining the science and data behind things hat make it into the media. It tells you where the news came from and gives links to the original research article.

It has a nice standard format and provide valuable insight into the research. I often come here right after reading some tidbit in the news tos ee if there is a nice post that easily explain the work. Much easier than doing it myself.

Then I can concentrate on all those stories that do not get followed by the NHS.

Vaccines reduce disease

200910191117.jpgby otisarchives4

How safe is Gardasil? And a new antivax FAQ

[Via Bad Astronomy ]

Fighter for truth and science Ben Goldacre tweeted a link to a nifty blog post showing just how safe the Gardasil HPV vaccine is. Using easy-to-understand graphics, the post (on the very nice Information is Beautiful blog) makes it very clear that comparing the good it does to the very tiny risk, Gardasil is a monumental achievement. Actually, just all on its own it’s a big advancement in the fight against cancer. The post also puts it in place among other low-risk dangers like getting hit by lightning or being killed in an earthquake. I like that; I myself have compared it with dying from falling off a chair.

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I am so glad to see this. I had seen the graphic all around the web but it had lost its link to the original. It helps place the risk in much better perspective. The risk-reward equations for vaccines is just not well understood by many people.

I have had people tell me that vaccines really do nothing, that polio and smallpox were not eradicated by vaccines but by better hygiene. Awfully coincidental. Let’s look at some data.


polio rates

This is from the CDC and shows the rates of paralytic poliomyelitis in the US (PDF). According to the CDC, the rates of polio had actually increased from the 1800 because of increased sanitation. IN those earlier times, children were probably exposed on a regular basis, even while in the womb, and developed immunity without the resulting paralysis. Polio is especially deadly the older the patient is.

As they state:

In the immediate prevaccine era, improved sanitation allowed less frequent exposure and increased the age of primary infection. Boosting of immunity from natural exposure became more infrequent and the number of susceptible persons accumulated, ultimately resulting in the occurrence of epidemics, with 13,000 to 20,000 para- lytic cases reported annually.

So, 20,000 cases down to 61 in 10 years. All after the vaccine was introduced. Let’s look at another disease. Measles:


measles

or Rubella:


rubella

or mumps (vaccine licensed in 1967)



200910191047.jpg

Just a coincidence that the numbers of people infected with these diseases dropped dramatically after the vaccine was licensed? I don’t think so.
We eradicated smallpox due to the use of a vaccine and are well on the way to eradicating the polio virus. The only time many of these diseases appear in the US is when a high enough percentage of people fail to get vaccinated. This causes herd immunity to fail, allowing the disease to spread to many susceptible people.
While the Amish do vaccinate themselves (there appears to be no religious reasons prohibiting vaccines. Surveys indicate that their main concern is ‘fear of side effects.’), the rates have often been lower than needed for herd immunity, resulting in outbreaks of serious diseases, such as pertussis, in their communities.
When people fail to get immunized, they not only put themselves at risk, they put others at risk also.
The disease can not spread unless there are enough people around who are able to spread it. For a lot of these illnesses, less than 85% immunized means that the disease can cause a lot of damage.
Vaccination has a strong community rationale. One that is some cases can be more important than a personal belief. It depends on just how dangerous a particular epidemic is to the community.
And vaccinations do reduce the spread of epidemics.