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A Man with a Ph.D. - Richard Gayle's Weblog
 Saturday, September 28, 2002
Pesticide resistance warning after gene discovery. Scientists have raised concerns following the discovery of a single gene that gives vinegar flies resistance to a wide range of pesticides, including the banned DDT. Australian Research Council [EurekAlert - Biology]
A single mutation in one gene can confer a wideranging resistance to a huge range of pesticides with very different structures. It will be interesting to understand how it does this. What is also interesting is that the mutation is obviously selective, since it has rapidly spread throughout the population. It may very well be that by selecting for resistance to say DDT, the fly mutated and now, even in the absence of DDT, this mutation confers a positive effect. This would be a nice example of the positive effect of selection on gene frequencies. It also means that we need to understand a lot more of cellular processes if we want to keep ahead of the genomes of the various pests. Those who propose that we return to DDT to kill mosquitoes in order to help people today should see this as a cautionary tale. We might effect short term gains in human lifes, while possibly degrading the environment and creating forms of insects that are immune to much more than DDT. Pest control is too complicated to envisage a single point of attack. 9:26:34 PM 
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SMU and UNC researchers make an advance in our understanding of gene regulation. Researchers from Southern Methodist University and the University of North Carolina have made an important advance in our understanding of gene regulation. The new insight comes from discovering the biochemical mechanisms by which an important protein works to silence genes. [EurekAlert - Biology]
Chromosomes are covered in proteins, producing chromatin. These proteins do many things, one being packaging the lond DNA strands into a small volume so that they can fit in the nucleus. In order for a gene to be transcribed and expressed, the relevant part of the chromosome must be unpackaged. This is a very complex process but one that we need to understand if we want to fully understand how the cell works. This may be one more step. 9:18:24 PM
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Friday, September 27, 2002
Stanford researchers find cause, possible cure for gluten intolerance. A team of investigators led by Stanford University researchers have discovered the cause and a potential treatment for celiac sprue, an autoimmune disease that leads to an inability to digest gluten, a major protein in wheat, rye and barley products. National Science Foundation [EurekAlert - Medicine & Health]
More about the 33-mer peptide that causes gluten intolerance. It affects 1 in 200 people and would indicate to me that eating grains is a rec our diet. 5:02:18 PM
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Home injury found to be a major cause of deaths, largest study of its kind finds. Home may be where the heart is, but it's also where danger lurks, new University of North Carolina at Chapel Hill research shows. More than 20 million visits to emergency rooms, doctors' offices and clinics occur because of mishaps there every year. [EurekAlert - Medicine & Health]
This reminds me of the man who slept on the sofa every day because he heard most people died in bed. Where do people spend so much of their time? Of course, the reason more people die in NM than MA per thousand could be interesting, or may just have more to do with doctors per thousand. The article does not clarify. 4:57:09 PM
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Researchers find trigger for devastating digestive disease, propose treatment. Researchers have found a peptide molecule that triggers celiac sprue [^] a severe inflammation of the intestine that results from eating wheat and related grains [^] and propose a treatment strategy that relies on bacterial enzymes to break down the offending molecule in the digestive tract. [EurekAlert - Medicine & Health]
Another instance showing how recent the eating of grains must be, since we still have immune problemswith the plants. This is a fascinating study. The undigestible 33-mer protein will cause havoc with the immune system, since it is geared to react to anything that large that is not 'self' as a foreighn invader. Maybe all we need to do is colonize the gut with bacteria that can digest this protein. The bbegs the question, why does that not already happen? 4:54:58 PM
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Blondes to die out in 200 years: "The last natural blondes will die out within 200 years, scientists believe. A study by experts in Germany suggests people with blonde hair are an endangered species and will become extinct by 2202. Researchers predict the last truly natural blonde will be born in Finland - the country with the highest proportion of blondes." [From the Desktop of Dane Carlson]
What a poorly written article. It does not say who is making this claim or how they actually arrived at it. The article claims that blondes are an 'endangered species'. News to me. Come on. The number of blondes found in the world may decrease, simply because there is greater gene flow than before (i.e. more Norwegians marrying Italians). The phenotypic expression of blonde hair may be reduced but the presence of the gene will not disappear. And then claiming, somehow, that bottled blondes are the reason??? Now, if blondes had less children than brunettes, thie lost of the blonde gene could occur. But they do not say this. In fact, if blondes do have more fun, they could have more kids, resulting in a higher frquency of the gene and a greater prevalence even irecessive.This looks lke an article that should have been published in the dog days of August. 4:10:24 PM
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Thursday, September 26, 2002
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Look several posts below for the wrong way to write this work up. This is how you write it up properly. The first paragraph sets the work up. Then the article explains some of the potential problems, before moving on to the nitty-gritty. This is how you make science interesting. Andrew Pollack did a fine job. The NYTimes opinion page may have a decidedly liberal bent but their science writing is consistently better than ANY other paper. 11:31:39 PM
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In Oxford Glycosciences Restructuring, Proteomics Will Play Second Fiddle [GenomeWeb]
Ex-Immunoid Michael Kranda looks like he got out just in time. He left in July. Another biotech starts crumbling. What I like is that proteomics are supposed to be 2nd fiddle, but will be in the black by next year. Oncology, their new focus, has no timeline to be profitable. What a shell game biotech is sometimes. Let's see, we will reorganize. fire people and refocus on a business model that has no prediction of when it will be profitable. I sure know that I want to invest in a company that thinks like this ;-) I think something got lost in the translation from English to American ;-) 11:04:27 PM
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Why Some With HIV Are Healthier. Wired News Sep 26 2002 3:12PM ET [Moreover - moreover...]
Very nice work but, @#$$%, I really hate how this science is reported. The first line is 'Researchers have solved a 16-year-old mystery of the AIDS virus thanks to a protein analysis technology.' It is not until you get to the end that you read this:
The Rockefeller researchers are now doing further work to find out exactly how the proteins block the progression of AIDS.
Other AIDS researchers said Ho's study, published in the journal Science, did not explain the whole story of long-term non-progressors.
The immune systems of non-progressor patients also make a compound called beta-chmokines. Their exact function remains unknown.
Ho stressed that much more work needs to be done.
'We wish to be somewhat cautious. I think it is not entirely clear whether we could take this discovery and turn it into a useful therapy,' he said.
So, they don't know what the proteins really do, they may not even be the whole story and they may not ever be a useful therapy. The scientists all say the proper things but the writer leaves people with the idea that the puzzle of non-progressors is almost solved. This is the 'TV model' of reporting. You hook the people with a teaser, usually giving some detail like ' Solving some disease'. Then after waiting for 20 minutes through the weather and sports, they finally tell you that the cure for the disease is still years away. But they got you to see the commercials, which is what their business really is. Cheap shots. This is really exciting work and a very nice use of technology. That is the wonder and the glory. But, NO, the media have to hype it up even more. 'Why Some With HIV Are Healthier'. We still do not know. We are just a little farther along the path of knowledge. Grrrr!! 10:54:54 PM
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Business Week:
In a previously unreleased letter obtained by BusinessWeek, the Centers for Disease Control & Prevention admitted that the CDC supplied Iraqi scientists with nearly two dozen viral and bacterial samples in the 1980s, including the plague, West Nile, and dengue fever. The letter, written in 1995 by then-CDC director David Satcher, was in response to a congressional inquiry.
[John Robb's Radio Weblog]
Remember, he was our friend then, fighting those nasty Iranians. Bummer. Hope we did not also ship him some weapons grade uranium ;-) 12:35:54 AM
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NYT. An article on the elimination of walk-ons for college sports. What a shame, but this report points to a bigger problem with the entire system: the US sports system from 9th grade on is much too elitist. We restrict access to athletics like it was a scarce commodity, treating it different than any other basic education.
In contrast, the USAF Academy (my alma matter) had a strong three season intramural program. They created this program because they felt that every graduate should graduate with some training in sports (and participate in its health benefits). This great experience is why I am so disheartened at watching my son traverse his large and expensive high school sports program. While I am confident he will make a team (basketball), he is unlikely to be able to participate in all the other sports he likes because the competition is too fierce for slots. He is one of the lucky ones. The overwhelming majority of other kids in school won't be able to play at all. Given the huge numbers of participants in the jr leagues for almost all sports in my town, there is obviously huge demand for an aggressive intramural program and the support to make it happen.
Unfortunately, it won't happen. The entrenched interests of the minority of parents that support the semi-pro elitist culture of high school sports will ensure that all of the towns sports funds get spent on the few and not the many. This elitism in high school and college sports is a hold over from the bad old days when only a very few were provided access to basic education and most were sent to trade schools (if at all). The time is ripe for a change in mindset. The first step is to change how sports are played in high school. We need to press the point that we would never restrict access to education in math and english education in the same way we restrict access to sports. We need to create an environment where sports education through three season intramurals is extended to all students as if it was a basic educational requirement. If we can change the way high school sports are played, college is likely to follow.
We may find that we like the result. [John Robb's Radio Weblog]
This is so right. A huge amount of money and time is devoted to the few. Why do colleges have great intramural sports programs, enlisting huge numbers of their students, yet public schools have none? Robb pretty much nails it. If I remember my 'Tom Brown's Schooldays' correctly, all the boys participated in rugby, not just the best ones. Physical exertion in team play was something everyone participated in. I think it would be better if we had more opportunity for that today. The mind is not as fully exercised unless the body is also. 12:26:31 AM
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Wednesday, September 25, 2002
Jackson researchers identify a gene implicated in oxidative stress and neurodegeneration. Researchers at The Jackson Laboratory announced that they have located a gene that protects certain brain and retinal neurons from oxidative stress, and prevents neurodegeneration. National Institutes of Health [EurekAlert - Medicine & Health]
Oxidative stress is a real problem following strokes also. A molecule I worked on, CD39, appeared to be upregulated (i.e. its expression was increased) in neurons for the first few hours following a stroke (actually, it was a murine model of stroke that could more accurately be described as a restriction of blood flow to the brain). CD39 seemed to have a pallitive effect in these murine models and may be part of the body's own defense against the damage from oxidative stress. Remember, oxygen is a 'bad' element and way too reactive for life. We can survive this reactive molecule because of the processes that cells have evolved to deal with it. They can carry out a tremendous amount of high energy chemitry by using oxygen. This makes life as we know it possible. Otherwise we might only be very primitive anaerobic bacteria. But oxygen, in the form of superoxide radicals, is always looking for an opening to cause real damage. We have good protection mechanisms but not always. 11:37:44 PM
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Rare disorder provides new insight into fighting infection. NIAID scientists and collegues found that an enzyme called caspase-8, known to help trigger apoptosis, is also involved in activating many immune system cells to fight off infections. This information, to be published in the September 26 issue of Nature, is the result of a study of an ALPS-like genetic condition known to exist in only two individuals. NIH/National Institute of Allergy and Infectious Diseases [EurekAlert - Medicine & Health]
Another valuable lesson about life in general and humans in particular. Just because we 'know' what a protein's function is, does not mean we know what a protein does. That is, the same protein in different cellular settings can have different purposes. This is one way that we can get by with only 50,000 genes or so. Some proteins do several different things. It may be a mistake to assume that a particular protein is only good for one thing. Especially a protein, such as caspase-8, which is an enzyme, usually responsible for clipping parts off of other proteins. Depending what other proteins are around, it can have drastically different effects. 11:31:43 PM
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Newly revealed viral structure suggests a continuum in the evolution of viruses. Scientists have uncovered the molecular-level framework of a common bacteriophage, a virus that infects bacteria. The results suggest that viruses developed a continuum of progressively more complex architectural strategies to cope with their increasing size as they evolved. The findings also may open a novel approach to developing therapies for certain difficult-to-treat bacterial infections. Human Frontiers Science Program, Natonal Science Foundation, National Institutes of Health, Fannie E. Rippel Foundation, Academy of Finland [EurekAlert - Medicine & Health]
I wrote about these techniques in some columns. The combination of X-ray crystallography and electron microscopy, coupled with novel software, is providing us with some incredible new views of microscopic life. Viruses have to solve some very simple problems. One is how to pack its genome into a protein shell. The larger its geneome is, the better it can cope with anti-viral mechanisms cells devise. The size of the protein shell limits the size of the viral genome (e.g. only so much volume for the viral DNA). So, if the virus needs a larger genome, it must come up with a larger protein shell to house the genome. This is not really an easy problem, so it is not surprising that different viruses have solved it in similar fashions. What is nifty are the details that are emerging regarding how they do it. 11:26:22 PM
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Tough Earth bug may be from Mars [New Scientist]
Okay, this is a report that overlooks so much as to make itself as sensational as possible. I wrote about this bug in one of my columns. Deinococcus has an amazing resistance to ionizing radiation. But this is because it has an amazing ability to heal DNA breaks. Radiation kills cells by destroying the DNA, breaking it into little pieces. Deinococcus can bring these small pieces back together with an amazing system. But it most likely did not evolve to resist radiation. There are lots of other environmental hazards that result in broken DNA, dehydration being one of them. It may very well be that Deinococcus evolved to survive habitats that had cycles of very dry conditions. Overcoming the resultant DNA breaks would have given it a selective advantage. This same process also gives it an advantage to ionizing radiation, but the radiation is NOT what selected for the survival trait. It is a common error for scientists to feel that if a trait is successful= it MUST have evolved FOR that purpose. But, life is adaptable and uses what it can to survive, to move around problems imposed by the environment. The trait we see may very well have come about for a reason totally different that the reasons we suppose. But, if for some reason the environment changed and ionizing radiation became a strong selective force, Deinococcus would have a selective advantage. But the trait was there before the particular selective pressure. Post hoc ergo propter hoc problems often abound when the media tries to explain science. 11:16:30 PM
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Tuesday, September 24, 2002
24-hour genome dawns. Nature Sep 24 2002 9:16AM ET [Moreover - moreover...]
Let's see billions of nucleotides per second. Think about it. Do we have technology that can ACCURATELY work that fast? Because you had better have a high accuract rate if you are going to make decisions based on someone's DNA sequence. Even if you had 99.999% accuracy, this would result in 50,000 errors, just about the same number of genes present in a person's DNA. If you screen 200,000,000 people, you are going to have a huge number of errors that could be crippling to people and the decisions they will make. Plus, just think of the storage needs for all this (2e8 people x 5e9 base pairs per genome is about 1e18 bits of info. This is a million terabits or 1 exabit.) Today, you need to sequence the DNA 5-12 times in order to overcome any potential errors. I suppose you could do the same here, but the need to accuracy is a whole lot higher than was used in the Human Genome Project.I still think the genome will be much more complex than many assume it to be. Trying to tailor a drug to an individual's system may require a far greater understanding of the biology involved that we currently have. 10:42:51 PM
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Need Biowarfare Agent? Hop Online. Anyone with Internet access can view the genome sequence of a bacteria that renders people feverish and disoriented -- and that was also built into bombs during the Cold War arms race. By Kristen Philipkoski. [Wired News]
Genome of potential bioterror agent seqenced. Scientists at The Institute for Genomic Research (TIGR), in collaboration with colleagues at Virginia Tech, the National Animal Disease Center and the Walter Reed Army Institute of Research, have determined the complete genomic sequence of Brucella suis, a bacterial pathogen and potential bioterrorism agent that could be targeted against humans or livestock. TIGR's analysis found "fundamental similarities" between the genome of Brucella [^] a pathogen that infects only animals -- and those of other microbes that cause diseases in plants. Defense Advanced Research Projects Agency, NIH/National Institute of Allergy and Infectious Diseases [EurekAlert - Biology]
The Wired article makes it seem somehow unethical to release the sequence. But you do not need the sequence to make Brucella bombs. If someone wanted to somehow mutate Brucella, they could do the science in secret. This is like Linux. Make it open and we can more rapidly adapt to something that nutcases create. If I remember correctly Brucella was the main reason you were supposed to cook lamb, pork etc. (non-bovine) really well and never eat rare lamb chops. 10:14:31 PM
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Humans and Their Closest Genetic Cousin, the Chimp, May Not Be So Close After All [GenomeWeb]
Study: Humans, Chimps More Different [AP Science]
Roy Britten and Eric Davidson were two of the most influential scientists I knew at CalTech 25 years ago. We got to work with Sea Urchins because of their work on development. The idea of master genes that regulated an organism's development was an eye-opener to me. I also learned about Cot curves and other (primitive) approaches to estimate DNA similarity. I love the idea that he used computer programs to analyze the differences. And this could be a huge difference, since it is likely that the real changes are in genes that affect morphology. I'll have to check out PNAS. 9:53:22 PM
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Sunday, September 22, 2002
Biotech Drug Copycats Get Ready to Pounce. iWon Sep 21 2002 6:52AM ET [Moreover - moreover...]
The last sentence is telling. Safety will be a big problem. J&J made a small change in its process for making EPO in Europe. Aplastic anemia turned up in detectable numbers of people, not everyone but some 10s of people per 100,000 taking it. Not enough to overcome the positive benefits. Except that the material made in the US by Amgen or even by J&J did not show this side effect. So, making a making a small change in the process resulted in a drug with a new detectable nasty side effect that was not there before. What will happen when generics, who are after cost cutting, get to work? Making a biologic that is helpful is a whole different ball game than a small chemical therapeutic. And, even with small chemicals there are noticeable side effects present in the generics that is not seen in the original drug. There really is a reason that the drugs are so expensive. It is not purely to line the pockets of the executives. 10:25:20 PM
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