parakkum

The wonderful power of Trehalose

I'm not actually sure if that link will work for people who don't have a subscription to Science Magazine, but it's about Huntington's disease and relates to some of what we work on in my lab, and specifically to work I've done with chemical chaperones. In short, they fed mice with Huntington's Disease a lot of the sugar trehalose and it reversed their neurological symptoms and kept their brains from plaqueing up.

Neat...and cool if it could be transformed into an effective therapy. There's nothing nice about death by dementia.

I just ordered ~$210 worth of primers for PCR reactions.

It's frequently unsettling to realize how easy it can be for us to spend money. Not like we're building Tokamaks or anything, but that's still a couple hundred bucks to buy about twenty short oligonucleotides at nanomolar concentrations.

Which will, I hope, fulfill my diabolic plan of knocking out certain ORFs. So there.

There are some signs that Ecstasy has neurotoxic effects vis-a-vis your serotonergic system (that is, it might not work so well after you use a lot). While this doesn't necessarily, say, cause depression (it might, might not) it might just make you suck at responding to changing situations:

Cognitive Inflexibility After Prefrontal Serotonin Depletion

The gist: When a monkey's prefontal serotonin system is jacked and you change a reward system that it has already learned, it can't adapt well. Worse, where a normal monkey eventually figures out that you're switching rewards and thus learns to adapt faster to reward switching each time, the depleted monkey never gets any faster.

Of course, it doesn't take this to convince me not to dose my brain with a chemical whipped up in a sink by someone who's taken less organic chemistry than I have. Gives me the shivers, that does.

An amazing result from work with Piraha tribe in the Amazon has shed some light on the importance of language in human cognition. You can read a summary on the Science web site, here:

http://sciencenow.sciencemag.org/cgi/content/full/2004/819/1

The Piraha have a counting system that goes "one, two, many." This lack of higher quantitation is pretty darn rare, and it may explain why they can't properly work with or conceptualize numbers greater than two. There are some dramatic experiments in the study, including one where Piraha are asked to duplicate a number of stripes written on a piece of paper (there's a picture of that in the story). When the number goes above two, they can't do it. In the example shown, they just keep drawing three stripes, even when there are more than that in the original.

The basic idea is that if you don't have a way to describe something, you can't think about it. Thus, people don't have an inherent number sense, and if a human lacks a word for a number, they can't operate well with it.

Pretty cool.

An article on the BBC about insufficient efforts to halt the spread of HIV in Asia, especially among intravenous drug users:

HIV warning over Asian drug users

Note this bit:

"Safe drug programmes work, say the authors of an editorial in the journal.

Despite this, authorities are concerned that they may encourage drug use."

Harm reduction works. Look to Australia. It doesn't increase drug use.*

*sigh*

*And even if it did, I'll take government-monitored junkies over world-spanning, terminal pandemic any day.

Less than 3.5 hours of exercise a week correlates with a 55% greater risk of early death...

Tsk. I used to exercise much more than 3.5 hours a week. Gotta get back on that schedule.

The date of earliest appearance of bunnies has been pushed back from about thirty-five million years ago to about fifty-five million years ago with the discovery of Gomphos elkema.

It had rabbit-like back legs, though its teeth and tail were more like those of a squirrel.

You can read the BBC story here.

That's still after the K/T boundary, though.

(But bunnies predate us by quite a while...)

Two reasons to wash your hands for at least fifteen seconds with soap after using the restroom and throughout the day:

1) So you don't spread disease to others

2) Because not everyone else is doing it...

...for example, the guy who came out of one of the stalls earlier today, rinsed his hands for a second in water, and then left. Trust me that any bug that can make you sick is fine with being moistened for a second or two.

Ick.

I just read through a number of papers concerning the coli gene dacC and its protein product, known variably as penicillin-binding protein 6 and as one of several D-alanyl-D-alanine carboxypeptidases.

The only problem here is that the second function, the carboxypeptidase function, has never been demonstrated. In fact, the one citation that tests this finds a lack of carboxypeptidase activity. It's simply that, over time, a reasonable surmise, based on other functional similarities such as penicillin binding and structural characteristics, changes into "fact," at least as far as scientists writing papers are concerned - even though it has been experimentally demonstrated to not be the case.

I've seen this many times before, as I'm sure most attentive people have. Something is stated as conjecture, a reasonable guess or a projection, and is then subsequently cited as fact.

There are so many circumstances under which this practice can be very damaging that it's a shame we aren't taught more about evidence in our primary educations.

Some notes on computational analysis of metabolic networks and path lengths within them, from Ma H, Zeng AP, Bioinformatics 2003, 19(2):270-7. PMID: 12538249

Background stuff: In previous work, metabolic networks had characteristics of small-world networks (most nodes with small connectivity, a few nodes very high connectivity – like WWW). Average path length (APL) for all metabolite pairs across 43 organisms was about the same, 3.2 (short). However, common intermediaries such as ATP are allowed as nodes, so going from one ATP-using reaction to another counts as “conversion,” even though the key metabolites from each reaction would take quite a few steps to mutually interconvert. The fact of in vivo irreversibility also badly breaks this network idea.

This study: Used KEGG LIGAND DB (has COMPOUND, REACTION, ENZYME). They corrected some mistakes in the KEGG info. Reaction direction is indicated on the KEGG displays, but not in the data (typical). They set a bunch of reactions as irreversible, yielding 2,000 irreversible reactions. When they make the graph representation, irreversible reactions are called arcs, reversible ones are called edges.

“Current” metabolites, which carry charge and functional groups, must be discounted – but not in some cases, then they actually are the key pathway constituents (and again, manual curation is necessary). They then looked at whether their network was still small world. Small world networks have a power-law distance between nodes, while random networks have a poisson distribution. They measure input and output values for each metabolite and find that it’s still a power-law distribution (small world). Having excluded the current metabolites, the top ten hub metabolites are pretty much the same across several organisms.

They then identified the shortest path length from one metabolite to all reachable metabolites by the ‘breadth first searching method’. Start with a metabolite M. All metabolites directly connected to M are in layer 1. All metabolites connected directly to a layer k, but not in any earlier layers are in layer k+1. The layer number is the path length from M to the metabolites in that layer (and maximal path length occurs when you run out of new layers). Given irreversible reactions, the path length from A to B is not always the path length from B to A. Using Glucose as an example: They were able to reach 386 metabolites from glucose (that feels like less than I’d expect, but that probably reflects KEGG’s limitations). Average path length is 7.68. The average path length for the whole metabolic network is 8.2. The network diameter (longest pathway length) is 23 for coli (based on KEGG).

Average path lengths vary a lot, and not exactly with network scale. Very small networks have a low AL, but that tends to be because they’re parasitic and many of their nodes have dropped out (where they piggyback on the parasitized organism). APL by domain: Eukarya (9.57), Archae (8.5), Bacteria (7.22), Bacteria w/out parasites (7.73). Diameters, same order: 33.1, 23.4, 20.6.

They suggest that it would be interesting to find the shortcuts that contribute to shorter APL in bacteria. I’m inclined to agree.

A very well-written bit about how the "culture of life" has managed to seriously miss the point:

Click here for the post

It does seem that the logical extension of the idea that "keeping a braindead body operating" is a good thing would be to take heroic measures to keep all bodies running at some level. After all, most deaths could be worked around for quite a while if all you needed to do was keep the majority of tissues perfused.

Sick, stupid and ultimately disrespectful of the dead and living alike.

I'm currently moving through the literature on RNase III. I'm in 1997 now (for my current work, it always pays to go older to newer, so I've been following the literature from the early work in the 60s toward the present). Up to 1997, very specific cleavage by RNase III had been demonstrated without identifying any conserved motifs that appeared in the cleavage sites. Zhang and Nicholson had the bright idea of comparing all the confirmed cleavage sites and figuring out what wasn't there, and in so doing turned up unfavorable base pairs that disrupt RNase III binding, preventing cutting at those sites. Thus, specificity defined by a lack of certain features.

I love papers like this.

The Pubmed entry for the paper. You can read the paper for free at PNaS or Pubmed Central, both of which are linked out from the Pubmed entry.

A chip implanted in a (paralyzed) man's motor cortex lets him use a GUI to control household devices.

The BBC story

I'm impressed by the long-term goal -- using a computer interpreter to bridge the severed gap between CNS and muscles, allowing movement for the paralyzed. I'd bet money on nerve regeneration working before this does, however.

I just hit this gem of a line in a paper I'm reading:

"The mutant has a large amount of 30 S-like RNA, but this difference seems to be only quantitative..."

Yes, it's only a quantitative difference, so it can't mean much. After all, whether I'm stung by one bee or a thousand bees, the salient point is that bee stinging has occurred.

Ahem.

(I know that there are situations in which the fact that something happens or not is more important than how much it happens. For example, one bee sting and three bee stings are probably about the same for someone suffering from severe anaphylaxis with no epinephrine handy. However, this specific example describes a situation where a substantial quantitative difference absolutely matters. I suspect the authors downplayed it because it didn't fit their conclusion.)

Well, behavior control and cancer detection.

Susana Lima and Gero Miesenbock at Yale wanted a better way to study the neural basis of behavior in vivo, allowing the study animals a full range of motion not achievable when hooked up to electrodes. To that end, they express an ATP-stimulated rat ion channel in flies, then load the flies up with "jailed" ATP that's stuck within another molecule and thus unavailable. A hit from a UV laser breaks the molecule apart, freeing the ATP and stimulating the ion channel.

...and the flies go wild, zipping around and being generally much more active than nonstimulated flies.

The Pubmed abstract is here.

Jochen Guck and Josef Kas at the Institute for Soft Matter Physics at Leipzig University have developed a test to evaluate cell samples for cancerous cells using a laser. Cancerous cells show varying degrees of cytoskeletal breakdown -- less of the cellular framework -- relative to normal cells. Thus, when struck by an IR laser, the momentum of the light is able to stretch cancerous cells much more dramatically than normal cells. They've reported correctly diagnosing cancers with as few as fifty cells, which is beyond the reach of most molecular biological methods.

Public Library of Science (PLoS) is a fairly recent concept for biology publications of making a freely available, open-access journal. General info about PLoS can be found here.

"The Third Age of Phage" is a primer on new doings in phage biology written by Nicholas H. Mann.

By his reckoning, the first two "ages of phage" were early interest in phage as possible antibacterial therapeutics (before the discovery of antibiotics) and then the subsequent use of phage for many, many years in basic biological research. Now...

"The third age of phage has begun only recently with the growing recognition that phages may be major players in the great planetary biogeochemical cycles [1] and also may represent the greatest potential genetic resource in the biosphere."

Some key points from the primer:

Phages are abundant, especially in our oceans.

"It is now widely accepted that phages with a very distinctive morphology, the so-called tailed phages (Figure 2), which dominate the marine virus population, represent the most abundant biological entities on the planet, and total phage abundance in the biosphere has been estimated at 10^30 or more [3]."

...and we don't know much about them:

"Approximately 65% of the sequences obtained in a 2002 study did not have homologues in the nucleotide databases, suggesting that marine viral diversity is largely unsampled."

Phages described in a paper by Sullivan et al contain a substantial set of genes, including a number of genes that code for cellular components. These can, for example, be activated even when the phage shuts down cellular gene expression, thus allowing key cellular functions that are necessary for phage replication for continue (after all, it's hard to replicate if you kill the cell instantly).

Naturally, this suggests that a whole lot of phage-mediated lateral gene transfer is going on in the ocean.

The ocean's full o' bugs.

Evolutionary biologist Ernst Mayer passed away this year.

Here's a good bio article about Mayer.

An Australian IVF patient is pregnant with her second set of quadruplets, and criticism is falling on the doctor involved. His response:

"I defend it in that what I did was to try and get this couple pregnant in the best way possible. There was always a slight risk of two or even three babies but I didn't expect to get four. It's certainly not something I wanted to achieve.

"The couple came back for more babies so soon because it took them 18 cycles to fall pregnant last time. You just cannot be absolute with this game," he said.

That is certainly true. There was no way of predicting quadruplets, as far as I know. However, they already had five children. They're in a first-world nation -- why do they need more than five?

More:

"Warren is a fantastic doctor and a wonderful man and without him we can't have children," said Darren Chalk. "A lot of people might criticise, but we wanted a big family and we're really happy."

Ick. Someone else ranted about this better than I can (from Spinnwebe): "It's less people, not more, you planet-killing morons."

The BBC story

Another PLoS primer, from Jerome M. Siegel:

Functional Implications of Sleep Development

Babies devote half their sleep time to REM sleep, whereas adults spend a paltry 20% of their sleep in REM. Two possible reasons are suggested:

Developmental buffering -- REM sleep provides generic neurological activity that can buffer against development of abnormal neural connections (as can happen, for example, if one eye is covered during early development). REM sleep deprivation actually hastens reorganization to yield abnormal connections.

Thermoregulation -- Deep sleep cools the brain, REM warms it. Very straightforward.

The meat of the primer is relating the findings of Karlsson et al in this month's issue. The very short of it is that sleep mechanisms in neonatal rats are similar to those in adult mammals, suggesting that change in the control elements is not the driving force in changes in sleep patterns as mammals age. I'll quote the primer here:

The upshot of these findings is a picture of a largely mature REM sleep generator mechanism at birth. The developmental progression of REM sleep signs, particularly the reduction in sleep duration and the development of the characteristic reduction in electroencephalogram voltage to a waking-like pattern in REM sleep, may result from the maturation of the targets of these brainstem systems, the modulation of these generator mechanisms by developing systems, or a relatively subtle maturing of connections within the REM sleep generator systems.

Nifty.

In this report, journalist Brian Deer looks into a new "disorder" that basically boils down to "women not being interested in sex."

I love the opening lines:

One way for drug companies to maximise profits is to encourage prescribing of their products to people who don't need them. Another, more daring, approach is to create new medical conditions...

The diagnosis of "sexual interest disorder" might apply to you if you're a woman who is not, at the moment, interested in sex.

Yes, that definition is exactly as retarded as it sounds. The point of the article is that new conditions are defined to drive pharma sales, and then pharma money in turn feeds back into the type of research that is done. Thus, the many reasons you might not be interested in sex -- perhaps you're busy on a really exciting project at work, perhaps your guy's a jerk, perhaps you need more sleep, perhaps it's just not important to you right now -- are ignored in favor of a pharmaceutical solution.

I am hardly opposed to pharm interventions. I like medications; they recently kept my neck from spasming indefinitely. But this is a good example of commercial interests driving medical research in a distinctly unwholesome direction. The real kicker on this whole story is that the "need" for widespread treatment for this condition is based on a solid misinterpreting of one sociological study.

Here's the work as quoted by Dr. Sandra Leiblum:

"Especially remarkable was the finding that one out of three women said they were uninterested in sex."

We'll leave the issue of whether or not that's remarkable aside. But consider the actual question asked by Dr. Edward Laumann in the study being cited:

"During the past 12 months, has there ever been a period of several months or more when you lacked interest in having sex?"

Somehow, that doesn't instantly translate into the absolute "one out of three" Dr. Leiblum threw out above. What portion of the sample set had kids? What portion had long work hours? What portion was single? (...and so on.)

Any female thoughts on this?

The first successful birth following transplantation of ovarian tissue has occurred. Stephanie Yarber, who experienced very early menopause, received ovarian tissue from her twin sister, Melanie Morgan and has given birth to a child.

You can read the BBC story.

Oddly enough, the oldest research article currently included in Pubmed describes a similar procedure carried out over a century ago:

Ovarian transplantation and reconstruction of fallopian tubes: with report of two cases and review of literature.

The penultimate line from the abstract: Neither of the recipients had begun menstruating postsurgery at the time of this article's publication (about 6 months postoperatively), but signs were hopeful.

I wonder, well after the fact, if the women involved suffered any complications, given that this was well before the discovery of histocompatibility (and soon after Landsteiner's elucidation of blood types) and they were most likely unrelated.

It's also worth pointing out that this abstract promises a "review of literature." Success has been a long time coming.

(For the curious, the actual point of this kind of transplantation is not the extremely rare case of identical twins, but to let you remove ovarian tissue from a woman who is going to be subjected to systematic treatments such as chemotherapy, later returning it so she can be fertile again after a procedure that might otherwise leave her sterile.)

In their recent paper in PLoS Medicine, Ezzati et al compared body mass index (BMI), cholesterol and blood pressure with national income, share of income spent on food and degree of urbanization across more than a hundred countries. The goal is to explore the link between development and the appearance of cardiovascular diseases.

Some observations from the paper:

Average BMI and cholesterol increase, then level off and finally decline with increasing national income except in the United States. BMI declines more rapidly at higher incomes for females than males again, except in the United States. I've cobbled together this figure from a much larger one to illustrate this point:

BMI-and-GDP

The first graph is men, the second women. Notice how at higher GDPs BMI in women drops off more rapidly than in men, but in both genders mean BMI is equal (and high) in the United States. As anyone who's traveled could tell you, only in the States are we both wealthy and enormous.

There's a strong positive correlation between urban living, BMI and cholesterol. Thus, as populations shift to urban living, they gain weight and have increased cholesterol. Indonesia and Nigeria buck this trend, having substantial urbanization without the same degree of increase in BMI and cholesterol.

There was no good correlation between anything and high blood pressure. The authors attribute this to regional differences in diet, which can directly influence blood pressure independent of other cardiovascular concerns.

The final paragraph:

The division between the diseases of poverty and affluence has provided a convenient tool for targeting policies towards risks such as undernutrition that affect the poor [56]. Demographic and technological change, however, are increasingly modifying the income patterns of cardiovascular risk factors and shifting their burden to the developing world. As a result, low-income and middle-income countries increasingly face the double burden of infectious disease and cardiovascular risk factors. Unless the research and intervention needs described earlier are pursued, this will create a world in which all major diseases are the diseases of the poor.

Both the authors of this paper and Thomas E. Novotny, in his review, infer from these results that we need to intervene with developing nations before they climb the slope of increasing BMI and related issues. A salient question, though, is whether we expect the developing world to act like us and just keeping getting larger, or act like the rest of the developed world and come back down to a healthier steady state.

An added thought: I'd really like to see a longitudinal version of this study.

From the official Chinese government news, an article on China's "9 steps to stop AIDS."

The article has no official current tally for HIV cases in China, but does have this statement:

Experts have warned that the number of HIV/AIDS carriers in China will reach ten million, if prevention and control measures aren't carried out and implemented in time.

By comparison, the current HIV tally in the States is just shy of a million, according to the CDC.

Perhaps sobering thought -- this means about every three hundredth person you meet* has HIV, on average (of course, in parts of Africa, it's every third person, which is stunning).

*assuming you're walking around in the U.S.

From the MMWR for July 1, 2005 (volume 54, number 25):

Annual Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses --- United States, 1997--2001

This report assesses the health consequences and productivity losses attributable to smoking in the United States during 1997--2001. CDC calculated national estimates of annual smoking-attributable mortality (SAM), years of potential life lost (YPLL) for adults and infants, and productivity losses for adults. The findings indicated that, during 1997--2001, cigarette smoking and exposure to tobacco smoke resulted in approximately 438,000 premature deaths in the United States, 5.5 million YPLL, and $92 billion in productivity losses annually.

Also:

During 1997--2001, [health care] expenditures plus the productivity losses ($92 billion) exceeded $167 billion per year.

Heat-Related Mortality --- Arizona, 1993--2002, and United States, 1979--2002

Findings indicated that, during 1979--2002, a total of 4,780 heat-related deaths in the United States were attributable to weather conditions and that, during 1993--2002, the incidence of such deaths was three to seven times greater in Arizona than in the United States overall. Public health agencies in communities affected by periods of extreme heat should educate populations at risk (e.g., persons aged >65 years) and consider designing and implementing location-specific heat response plans (HRPs).

Update: Influenza Activity --- United States and Worldwide, 2004--05 Season

During the 2004--05 influenza season, influenza A (H1),* A (H3N2), and B viruses cocirculated worldwide, and influenza A (H3N2) viruses predominated. In addition, several Asian countries continued to report widespread outbreaks of avian influenza A (H5N1) among poultry; in Vietnam, Thailand, and Cambodia, these outbreaks were associated with severe illnesses and deaths among humans. In the United States, the 2004--05 influenza season peaked in February, was moderate, and was associated predominantly with influenza A (H3N2) viruses.

And:

As measured by the 122 Cities Mortality Reporting System, the percentage of deaths in the United States attributed to pneumonia and influenza (P&I) exceeded the epidemic threshold§§ during 8 consecutive weeks ending February 14--April 9, 2005, and peaked at 8.9% during the week ending March 5, 2005 (Figure 2). The percentage of P&I deaths remained below the threshold through the weeks ending April 30--May 21, 2005. During the previous three influenza seasons, the peak percentage of P&I deaths ranged from 8.5% to 10.4% (1; CDC, unpublished data, 2005).

QuickStats: Percentage of Adults* Who Reported Being Deaf or Having a Lot of Trouble Hearing Without a Hearing Aid, by Sex and Age Group --- United States, 2003

The upshot: Men lose their hearing faster than women. This difference is most notable between ages 45 and 74.

From the MMWR for July 8, 2005 (volume 54, number 26):

State Smoking Restrictions for Private-Sector Worksites, Restaurants, and Bars --- United States, 1998 and 2004

Secondhand smoke is a known carcinogen. Exposure to secondhand smoke causes approximately 35,000 heart disease deaths and 3,000 lung cancer deaths among nonsmokers in the United States every year.

One of the national health objectives for 2010 is to establish laws in all 50 states and the District of Columbia (DC) that prohibit or restrict smoking in public places and worksites. A related objective calls for all worksites to voluntarily implement policies that prohibit or restrict smoking.

During December 31, 1998--December 31, 2004, 10 states indicated changes in the level of their smoking restrictions for private-sector worksites, nine states indicated changes in the level of their smoking restrictions for restaurants, and five states indicated changes in the level of their smoking restrictions for bars, on the basis of the STATE System coding scheme. In every case, the restrictions became more stringent.

Much to my surprise, in none of the categories evaluated was California the most restrictive state.

Assessment of Local Health Department Smoking Policies --- North Carolina, July--August 2003

North Carolina's state smoking laws actually limit the restrictiveness of local smoking laws, except in the case of local health departments. Not all LHD directors are aware of this, however:

Among the LHD directors, 57 of 75 (76.0%) said they were very familiar or somewhat familiar with the preemptive provisions of North Carolina's state law on smoking in public places (9). However, 28 of 75 (37.3%) incorrectly believed the law prevented enactment and enforcement of a 100% tobacco-free policy on LHD grounds, and 15 (20.0%) said they did not know whether the law prohibited such a policy.

Progress Toward Poliomyelitis Eradication --- India, January 2004--May 2005

Since 1988, the global incidence of polio has decreased by more than 99%, and three World Health Organization (WHO) regions (Americas, Western Pacific, and European) have been certified as polio-free (1). India, the largest of the six countries where polio remains endemic, experienced a large polio outbreak (1,600 cases) in 2002 (2). Since then, the Government of India (GOI) has accelerated its polio eradication activities by increasing the number and quality of supplementary immunization activities (SIAs),* which reduced the number of reported cases to 225 in 2003, 134 in 2004, and 18 in 2005 (as of June 18) (3). During 2004 and early 2005, taking advantage of the geographic restriction of wild poliovirus (WPV) circulation, GOI and its partners launched several immunization and surveillance strategies to maximize the probability of eliminating poliovirus transmission in India. With continued high-quality interventions, interruption of WPV transmission in India by the end of 2005 appears feasible

Of course, Africa is still a problem, especially with Islamic religious leaders in northern Nigeria spreading rumors about the vaccine (from 2003). The hit they took in missed vaccinations let Polio spread back into neighboring countries that had been previously cleared.

The BBC story

The four major nerves, which used to go down Jesse's arms, were dissected from his shoulder and transferred on to his chest muscles.

He can now raise his elbow, open and close his hand and rotate his hand and lower it.

I didn't realize the technology was that advanced. It's needed:

There are thought to be over 500 service men and women who have returned to the US from Iraq and Afghanistan as amputees and Dr Kuiken said he hoped that the groundbreaking technology could be used to help them.

From the MMWR for July 22, 2005 (volume 54, number 28)

Epidemiologic Assessment of the Impact of Four Hurricanes --- Florida, 2004
Carbon Monoxide Poisoning from Hurricane-Associated Use of Portable Generators --- Florida, 2004
Disparities in Universal Prenatal Screening for Group B Streptococcus --- North Carolina, 2002--2003

Researchers in Italy directly tested the River Po for a unique cocaine metabolite, benzoylecgonine. The amount they found suggests that cocaine use is triple that estimated based on crime stats and population surveys:

They say they found the equivalent of 40,000 doses a day in the Po valley, home to about five million people.

The BBC story

Innovative approach to drug testing. They're planning on testing for marijuana next.

A check done on 147 chickens on sale in the UK showed that over half contained multi-drug resistance E. coli and about a third had bugs resistant to Trimethoprim, which is used to treat bladder infections.

Here's the BBC article.

Naturally, this raises the concern that antibiotics used in livestock production are leading to more antibiotic-resistant bugs in our food, and subsequently to more difficult-to-treat infections in people. On the other hand:

The British Poultry Council disputed the validity of the survey, saying it was not detailed enough and that previous research pointed to lower levels of antibiotic resistance in chicken.

Spokesman Darren Pearson said: "There's overwhelming evidence that the main reason for antibiotic resistance in humans is because of the antibiotics prescribed for us rather than animals.

There are problems with Pearson's statement. Yes, most antibiotic resistance in humans does appear to be due to use in humans, but there aren't many good studies about the effects of the widespread use of low-level antibiotics in animals. Search Pubmed, and you'll find papers that amount to:

"Resistant bugs come from outside hospitals. They're probably from livestock."

"Here are all these reasons why we think it's not the fault of antibiotic use in livestock, so stop worrying."

"Antibiotic resistance is bad! We need to worry about overuse in livestock."

"What about pets? They use drugs in pets, too."

Notably, the field is rife with opinions, yet sparse with research studies. Part of the problem is funding, of course. The big money here is on the side of livestock producers, who aren't about to fund research into their role in increasing antibiotic resistance. That's why even naysayers don't have evidence to back up their intuition (and they may be right, they just don't know).

It would be good to figure it out, though.

As has been noted, Americans are fat and the trend is that we're becoming fatter.

If you'd like to read the source for that BBC story, here's the 2005 issue report on obesity from the Trust for America's Health. I've just skimmed it so far, but some worthwhile bits:

Physical inactivity is a major health threat independent of obesity

The U.S. government lowered the BMI cutoff for "overweight" in 1998 to better match actual healthy body weights, from 28 in men and 27 in women to 25 overall. "Obesity" currently begins at a BMI of 30.

Some have recommended setting the overweight and obese BMI cutoffs to 23 and 25, respectively, in Asians.

California is the thirty-first most obese state of fourty-nine counted. Hawaii was not included in the study.

On a related note, a 32-ounce Big Gulp of Coca Cola contains 43.2 grams of sugar, or 14.4% of your carbohydrate RDA. You could also get a 64-ounce Double Gulp, of course, for over a quarter of your carbohydrate RDA. According to their trivia page, 7-11 sold 33 million gallons of fountain drinks last year. That's over 5,700 metric tons of sugar, or the carbohydrate requirement for 52,000 people for a year. Sweet.

A research team managed to film an adult Architeuthis in its natural environment, 900 meters below sea level. They used a shrimp lure to draw it in. Unfortunately, it was snagged and lost a tentacle before escaping. Based on its escape attempts, the squid appears to be rather more energetic than had been previously assumed.

The BBC story, which has links to video.

The article also discusses how the fishing practice of bottom trawling may be destroying squid egg beds on the sea floor. Their evidence for this is indirect -- sperm whales swimming through areas that were traditionally rich in giant squid are no longer able to find squid to eat.

Robin Warren and Barry Marshall have received this year's Nobel prize for medicine for discovery that Helicobacter pylori causes the majority of ulcers.

The BBC story

The high point in this story is that Marshall infected himself with pylori to convincingly demonstrate that it did, indeed, cause ulcers.

This discovery represented a major paradigm shift in approaching a condition that was thought of as a purely physiological response to stress and anxiety, best treated by watching what you eat. I recall back when I was at Berkeley reading a textbook on physiological disorders that preceded the widespread acceptance of this idea and discussed lifestyle changes oriented toward reducing stress and anxiety as the only treatments. It certainly made me wonder about all the other conditions in the book that were also attributed to anxiety. More paradigms waiting to shift, perhaps.

Tool use was observed for the first time in wild gorillas, as reported by Thomas Breuer, Mireille Ndoundou-Hockemba and Vicki Fishlock in their paper in PLoS Biology. One gorilla broke a branch off and used it to test depth in murky water; another used a broken-off branch to steady itself and then as a bridge over swampy ground.

You can also read about it in the handy synopsis written for the general reader.

This is a big deal, inasmuch as gorillas have been taught tool use in captivity but it hadn't ever been observed in nature. The thought is that they live in such food-rich areas that they don't typically need to resort to tool use to survive.

A much-delayed paper on which I am an author has finally hit publication, bringing my grad school tally to four, roughly a year after I finished. It's a pretty cool paper, too.

It would take the energy from the sugar in about two and a half cans of your favorite soft drink to unwind all the DNA in your entire body with the Rep helicase.*

Not that that's just going to happen if you have too much soda, or anything like that.

*An enzyme that unwinds DNA so it can be replicated.

Well, I'm excited. :)

Researchers in central Borneo have photographic evidence of what appears to be a previously unknown mammal, possibly in the viverrid family, which includes mongooses and civets.

You can see one of their pictures at the BBC story.

They captured the pictures using IR-activated cameras left on forest trails.

On the upside, it's amazing to find a new, fairly large mammal these days. The downside, however, is that it may have been findable due to increasing destruction of forest habitats, thus making its territory more accessible to the researchers.

The BBC is reporting that the Seoul National University investigative team has determined that Hwang Woo-suk's group did, indeed, fake their cloning results.

The BBC story

A slightly more dated story in Science magazine gives us some background:

Hwang said, "I want to make it really clear that our research team produced patient-specific (stem cells)." He acknowledged, however, that the team had problems with their cell lines. He said that last January, contamination with yeast had destroyed at least six of the lines the team had created. Based on Hwang's statement, it's not clear whether any of these original six lines were alive at the time the Science paper was submitted in March. The group was "lax in our management and committed many mistakes," said Hwang. He said they would thaw the five remaining cell lines to try to demonstrate that they match their donors, a process that Hwang said could take about 10 days.

Hwang also said that MizMedi [the hospital that collected ova for the work] might be responsible for mixing up cell lines from its own research with those used in the experiments that produced the Science paper, and he called for an investigation. Roh held an emotional press conference shortly thereafter in which he reportedly reiterated his claims and accused Hwang of lying.

Several of their paper figures were direct duplications of other images - I'm amazed that people ever do this. Though Science magazine is planning on testing all figures in the future for photomanipulation, the Science article accurately points out that the peer review process is not designed to detect outright falsification. This is true -- as a reviewer, you basically assume that the actual data being presented is not being faked. And the truth is, if it is fraudulent, it will come out. This is the most incomprehensible part about faking scientific work. If you're working on anything that's at all worthwhile, someone will try to build on your work and find out that you lied.

From the Science article:

George Daley, a member of the Harvard group, says it is too early to tell how flawed the 2005 report is. "Hwang's group was skilled enough to be capable of doing what they claimed," he says. "We'll see how much of the Hwang methodology proves useful when we and others attempt to incorporate it into our own work."

It looks like Hwang's work itself is bunk, but hopefully others can make it work. The scrutiny will definitely be there when the next results are announced.

As discussed in this Al Jazeera article, a University of California study has shown increased risk for kidney failure with obesity; this is even after controlling for the high blood pressure and diabetes that often accompany obesity and which are also independent risk factors for kidney failure.

Dr Chi-yuan Hsu, an assistant professor of medicine and lead author of the study, said: "There are more and more people with kidney failure, but it hasn't been appreciated much that kidney failure can be a consequence of obesity."

Even moderately overweight people had a higher risk of kidney failure than people whose weight was in a normal, healthy range, he said. And for the morbidly obese, the risk was more than 700% greater, Hsu said.

The Summer, 2005 issue of Biomedical Computation Review lists the following as the top ten challenges of the next decade in computational biomedicine:

1. In silico screening of drug compounds
2. Predicting function from structure of complex molecules
3. Prediction of protein structure (from sequence)
4. Accurate, efficient and comprehensive dynamic models of the spread of infectious disease
5. Intelligent systems for mining biomedical literature
6. Complete annotation of the genomes of selected model organisms
7. Improved computerization of the health-care system
8. Making systems biology a reality
9. Tuning biomedical computing software to computer hardware
10. Promoting the use of computational biology tools in education

1, 2 and 3 may be more distant than the next decade, while 9 seems like more of a continuous process than a specific, finite challenge.

Full resolution of 5 requires really solid natural language processing, but in the meantime, tools will be developed that really accelerate literature mining by humans. Effectively, "semiautomated" mining is already becoming a reality.

8 has been more of a standards issue than anything else, and there are attempts to have everyone use the same formats for their systems biology models and information as a consequence.

10 would be a good gain -- I was barely exposed to the available computational biology tools when I was an undergrad, not really touching on their use in any detail until grad school. Given the open set of data which biology comprises, it would be helpful to orient students to the tools available to them to find the information they need.

This BBC article reports that Dr. Jon Sudbo of Oslo's Norwegian Radium Hospital completely fabricated his patient data for an article in the medical journal The Lancet titled Non-steroidal anti-inflammatory drugs and the risk of oral cancer.

From the article:

Stein Vaaler, director of external relations at the hospital, added: "He published an article in The Lancet in October last year whose data is totally false, actually totally fabricated.

Norwegian daily newsaper Dagbladet reported that of the 908 people in Sudbo's study, 250 shared the same birthday.

The editor of The Lancet reiterated the point that peer review only targets bad science, not fraud. Notably, in many cases of scientific fraud, there's a certain amount of sloppiness; Sudbo repeating birthdates, Hwang's group reusing different parts of the exact same image, Jan Hendrik Schoen reusing the same graph to represent completely different experiments. Does this mean that people who commit fraud are foolish or pathological enough to not worry about such oversights, or that we're just not catching the clever ones? I'm inclined to believe the former, because there's the fundamental problem in science that if your work is of any significance at all, someone will attempt to build on it -- so the discovery of fraud is guaranteed.

I've personally experienced this in a slightly different scenario, where it was not fraud but an experimental artifact (that is, an effect that appeared under a certain set of experimental conditions, but which did not indicate what the researcher thought it did). Several labs, including ours, tried to build on a result reported by another lab; all the labs found that the reported effect did not have the consequences it should have. Taking a step back, they tried to directly replicate the result and found they couldn't. They had a talk with the reporting lab, who went back, did more experiments, and discovered their error. If your work means anything, it's just a matter of time before someone else tests it.

Just so m will never go out into nature ever again:

Prions bind to soil and remain infectious

The Public Library of Science is an ongoing effort toward open-access science -- that is, not forcing you to have a subscription to read new articles and, ideally, letting a reasonably interested layperson understand why the work in question is important. To this end, PLoS has a number of peer-reviewed journals that feature significant, cutting-edge research with the bonus of an added explanation for the general reader, written by a science writer. In other words, the kind of thing you'd read in Popular Science magazine.

As part personal exercise and part encouragement to others to at least read the summaries, I'm going to start putting up some brief comments on the articles that excited me from the PLoS Journals. That I'll do in the extended.

Back again with some highlights from the August, 2006 issue of PLoS: Biology. This time, it's understanding the structure of the cell's protein recycler, seeing how photosynthesis makes its way around the ocean, understanding why we have genders and determining whether dinosaurs were hot- or cold-blooded.

Full notes and links in the extended entry.

Chimpanzees in West Africa adopt a specific strategy to cross roads, using a version of a strategy originally applied to approaching watering holes when predators are about.

The BBC story

As I walked out of the apartment to do some laundry last night, I ran into a troupe of four raccoons foraging in the grass nearby. They paid me very little heed, coming to within a meter or so as they looked around. They dug, sometimes shoulder deep, into the soft dirt and groundcover nearby. I don't know if they had any luck, but after about the fourth photo, they moved on. More pictures in the extended.

Edit: I just noticed the pictures in the extended may be displaying a touch clipped. I recommend clicking through to the Flickr photos themselves to see the full pictures.

A research team at Newcastle University in the UK has developed "micro livers" by successfully inducing cord blood stem cells to differentiate into liver tissue under simulated weightlessness.

Professor Colin McGuckin, part of the research team from Newcastle University that created the livers, said they could be used to end drug trials using animals or humans.

But by using the mini-livers we have developed there is no need to test on animals or humans."

Professor McGuckin overstates the case, although this is still an amazing development that will allow a lot of testing outside of animals and people. Unfortunately, all toxicity isn't liver toxicity -- witness the muscle-wasting effects of certain cholesterol-lowering drugs (statins) and the occasional psychotic break induced by psychiatric medications. Any one component of the system just can't stand in for the system as a whole.

That said, the liver is probably the most frequent toxicity target, so the ability to rule out drugs that have a toxic effect in micro livers is a solid gain.

The al Jazeera story

As I mentioned earlier, lab and computational biology are very different.

Witness my fourteen-hour day today, spent largely in a refrigerator.

Tomorrow, back to the computer.

That's the cover of the 6 April 2007 issue of Science magazine. Inside that issue, Sutter et al describe how they identified a single gene that appears to be the major controller of body size in dogs -- which, as the cover blerb points out, have the widest range of body sizes of any terrestrial vertebrate species.

You can read the article abstract here, and read the entire article if you have access to Science content (by, for example, being an AAAS member).

The cover is just great. The dogs, with their matched kerchiefs, look like total buddies, completely unaware of their size difference.

So this evening, I was wondering if you could power a hamster off a USB port. Let's do a rough calculation...

A USB port is rated up to 500 mAmp and 9 V. This comes to 4.5 W, or 4.5 joules/second.

Per Nutrient Requirements of Laboratory Animals, Fourth Revised Edition (National Academy Press), a small hamster (45 grams bodyweight) consumes 109 kilojoules/day.

So, you'd need 6.73 hours to recharge a hamster for a day of hamstering via USB port.

So now you know.

The BBC reports in this article about a new strain of cow isolated in New Zealand that makes milk that is low in saturated fats. The suggestion is that this could open up a whole new area of milk production, with cows making "skim milk" directly. One upshot there is that you no longer have to separate out so much fat yourself, and you're not stuck holding a bunch of fat you can't use.

The odd bit that clicked for me, but which wasn't mentioned in the article, is that surely dairy cattle with "low fat" milk can't properly feed their own young. After all, whole milk is pretty much exactly what a growing calf needs. Functionally, I'd expect these cattle to be like seedless fruit, requiring special outside assistance to get each new generation to grow.

Of course, I know so little about dairy production, I may be missing the fact that it's already done this way...

One of my favorite biology papers, perhaps ever, is a 2002 article by Autumn et al titled Evidence for van der Waals adhesion in gecko setae. You see, geckos run on walls, and they do it using setae, little hairs on their feet. For years, people have pondered just how that works, and in this 2002 paper, Autumn tested various hypotheses and found that van der Waals forces were to blame.

Even if you only ever had the one college (or even high school) chemistry class, that name may ring a bell. van der Waals forces, also called dispersion forces, are attractions that form between adjacent molecules based on temporary dipoles. In other words, the electrons in Molecule A happen to shift to the left, creating a net positive on the side facing Molecule B, so the electrons in Molecule B shift to match -- instant (temporary) dipole, instant (temporary) attraction.

So this seemingly obscure fact you learned in high school chemistry keeps geckos stuck to walls. I love that.

In a recent paper titled Carbon nanotube-based synthetic gecko tapes, Liehui et al have (in their words) "developed a synthetic gecko tape by transferring micropatterned carbon nanotube arrays onto flexible polymer tape based on the hierarchical structure found on the foot of a gecko lizard." In fact, it has "peeling and adhesive properties better than the natural gecko foot."

That's one less roadblock on the road to synthetic geckos. More practically, it's a demonstration that something as seemingly random as a biologist figuring out why geckos stick to walls may generate something as useful as "tape that reversibly sticks to anything."

In their paper titled Amyloidogenic potential of foie gras, Solomon et al examine whether foie gras might have the potential to pass on amyloid conditions (diseases that involve protein plaques, similar to but not the same as "mad cow"). If you're wondering why they even thought of looking for this kind of thing, here's the key driver from their introduction:

AA amyloid deposits are commonly found in waterfowl, particularly Pekin ducks, in which the liver is predominately involved (8-10). This pathological alteration is noticeably increased in birds subjected to stressful environmental conditions as well as to the forced feeding that is used to produce foie gras (8).

The punchline is that yes, the amyloid in foie gras can induce amyloid conditions in internal organs of mice that are either injected with or fed the protein in question. This suggests, in turn, that foods with high amyloid content may contribute to amyloid conditions, much as prions in beef can lead to encephalopathies in humans.

It's not at all uncommon for effects that occur in vitro (in test tubes, basically) to fail to match effects that occur in vivo (inside the living organism). It's always pleasing when we can figure out one of these discrepancies.

In a recent article in PLoS One titled Lectin-Based Food Poisoning: A New Mechanism of Protein Toxicity, Miyake, Tanaka, and McNeil resolve a curious discrepancy between what happens inside your intestines and what's been seen in the lab. It's been known for a long time that ingesting lectins -- proteins that bind carbohydrates -- from certain improperly cooked vegetables can cause toxicity, including nausea and diarrhea. This lectin exposure causes cell death in those cells lining the intestine, but, confusingly, cause no toxicity when directly applied to cells in culture, even at very high doses.

In this study, the researchers tested a novel hypothesis -- perhaps lectins don't affect intact membranes, but instead mess with membrane repair? Indeed, your intestinal cells are subject to a host of stresses, and are constantly repairing their membranes via exocytosis, a process lectins are known to inhibit. The researchers damaged the membranes of individual cells with a laser or with physical abrasion and then tested their ability to fix themselves in the presence or absence of lectins. They found that, fitting their proposed model, lectins stuck on the cells' surfaces dramatically inhibited membrane repair.

This is a clean, classic science piece, putting together a number of observations to make a new hypothesis, and then testing that hypothesis. It's also a good reminder that your intestines are a very dynamic place, constantly undergoing damage and reconstruction.

For a long time, the apparent similarity between pterosaur skulls and those of skimming birds, such as the black skimmer has led many people to belief that pterosaurs were likely to have fed by skimming. Skimmers fly very low over the water, dragging the bottom part of their beak in the water and snapping up prey on contact.

In their paper titled Did Pterosaurs Feed by Skimming? Physical Modelling and Anatomical Evaluation of an Unusual Feeding Method, Humphries, Bonser, Witton, and Martill use physical models to actually test the feasibility of skimming as a feeding method for pterosaurs.

In short, it couldn't have worked.

The researchers made physical models, both of the beaks of modern skimmers and of the mouths of pterosaurs, and tested them in a water-based drag testing facility. In so doing, they learned that modern skimmers actually burn more energy than we've suspected during their skimming activity, and that no pterosaur larger than about one kilogram could have managed the energetic costs of skimming.

In their closing discussion, the authors point to the dangers involved in using superficial morphology to guess at functional similarity. In addition to the need to physically test things as they did, they also mention that many people who made the superficial comparison between skimmers and pterosaurs ignored just how specially adapted skimmers are to their feeding style, with many skull traits that simply aren't present in pterosaur skeletons.

I'm a big fan of actually going and testing long-standing suppositions, so I really appreciated this paper.

Fun quote of the conference I'm attending goes to Jan Mrazek of the University of Georgia, discussing the putative role of Simple Sequence Repeats (SSRs). One prevailing thought has been that they're involved in phase variation (a defensive mechanism by which bacteria switch certain genes off and on as needed). Here's Jan's answer to his own question about whether SSRs are always indicative of phase variation in nearby genes:

"I think not, as most of these genes are essential, so it would not be useful to have phase variation unless you want to randomly kill yourself from time to time."

Mitochondria, the little energy factories populating our cells, have been implicated as key players in a number of cancers and in aging. Specifically, examination of mitochondrial DNA (mtDNA -- the mitochondria carry their own little bit of DNA, separate from the rest of your genome) from cancerous and aged cells seems to show a high rate of mutations. This may, in turn, play into the outcomes seen in aging, cancer, and related conditions.

The latest trick involves looking at mtDNA from single cells. This lets researchers examine cell-by-cell variability, and draw conclusions about the prevalence and significance of mutations in mtDNA. One of the problems of working with such exquisitely small samples, however, is contamination.

In their own single-cell mtDNA work, Yao, Bandelt, and Young noticed that some of their results seemed a little off. In a recent paper titled External Contamination in Single Cell mtDNA Analysis, they turn their efforts directly into evaluating just how often contamination occurs.

They lead by stating that roughly a third of all mtDNA results in the lab are caused by known contamination sources -- the kind you should already be controlling for. These include sample cross-contamination, and mtDNA from lab workers. One curious consequence of the latter source is that all the researchers must have their mtDNA sequenced so that researcher-originated contamination can be easily identified, and those results tossed.

They very cleverly address the problem of other, harder-to-find, contamination by comparing results to the available phylogeny of sequenced mtDNAs. In other words, they compared their samples to what we know about mtDNA from around the world to ask, "Am I seeing a lot of mutations, or is this random contamination from an unrelated individual?" Using these methods, they determined that once cross-contamination and researcher-sourced contamination are accounted for, a 0.6% contamination rate remains. This is significant, since researchers doing single-cell mtDNA analyses are hoping to find rare mutational events that lead to better understanding of cancers, aging, and other issues.

The authors conclude by recommending that in addition to the more obvious checks, all results should be evaluated against the global mtDNA phylogeny to help stamp out this last 0.6% of contamination errors.

I have to applaud the authors for their thoroughness, as well as their willingness to point to some of their own, earlier work, as an example of research that suffered due to this contamination issue.

I'm on a fact-checking and quality-assurance appreciation kick recently.

In their paper titled Sequence Polymorphisms Cause Many False cis eQTLs, Alberts et al take a look at the reliability of using gene expression data to find quantitative trait loci, areas of the genome that are closely tied to a given trait. QTLs are the kind of thing you hunt for when you're trying to figure out where a predisposition to schizophrenia comes from, for example.

In the eQTL method, gene expression data (rather than sequencing of actual genomes) is used to try and identify QTLs. However, as the authors tell us, small differences in the sequence of the same gene within your pool of sample sources can be a big problem for this method. A single nucleotide change in a gene may mean that its RNA no longer hybridizes nearly as well to the cognate probe sequence on the expression chip, thus giving an artificially low expression reading. As a consequence, you may inadvertently end up detecting minor genetic variations between your research subjects, rather than significant differences in gene expression that will help explain whatever it is you're researchers.

The authors present us with a statistical method that aims to clear out these erroneous results, thus settling the data set down to genuine expression differences that can be used to find QTLs.

This is another case of a group having an eye for detail and catching a potentially very problematic hiccup in an otherwise handy analytical system.

Titles from the morning session of the conference I'm attending, in lolcat:

EVIDENCE AN INFERENCE: PATHS OV CURASHUNS

QUIRKY SEARCHEZ: ANNOTASHUN IRREGULARITIEZ BIAS DATA 4 CURASHUN

GENE SUMMARIZR: SOFTWARE 4 AUTOMATICALLY GENERATIN STRUCTURD SUMMARIEZ FRUM BIOMEDICAL LITERACHUR

Indeed.

As the resident biologist, I've been asked by friends and family about the significance of the recent research paper describing the generation of apparent stem cells from, well, non-stem cells. Here goes.

The paper in question is "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Stem Cells," headlined by lead author Junying Yu, and coming out of the stem-cell powerhouse state of Wisconsin (not being facetious here, incidentally -- they really have led the way on stem cell work).

You can click here to go the article's PubMed citation. You'll need a Science subscription or institutional access to be able to read the actual article.

They started from the known fact that fusing an embryonic stem cell with a myeloid precursor (a "pre white blood cell", basically) effectively "reprograms" the myeloid cell into a stem cell. With that in mind, they made a list of genes that are highly expressed (lots of message output) in embryonic cells but not in myeloid cells. These are good candidates for the embryonic "on switch(es)" that lead to having stem-cell-like behavior. They organized this list in terms of which genes were already known to be involved in pluripotency -- that is, the ability to become any cell type. This is what we're looking for in stem cells, after all.

A set of these genes were then placed in a lentiviral vector. Lentiviruses are slow-growing viruses that can incorporate themselves -- and any passenger DNA loaded into them -- into the genome of a target organism. HIV is the best-known lentivirus. Based on their useful DNA-incorporating traits, lentiviruses are often used for work of this type.

The loaded lentivirus was then used to incorporate these genes into a line of hematopoetic (blood-forming) cells that were themselves originally derived from embryonic stem cells. They saw an increased expression of a gene that's normally seen only in stem cells, as well as stem-cell-like morphology, and the ability to make tumor-like growths in immune-compromised mice. So far, so good.

The group then winnowed down the genes until they were left with a set of four -- or possibly three. Three genes they found to be absolutely required for this transformation from somatic (normal body) cell to stem cell. The fourth gene significantly increases the efficiency of the process, and so they decided to keep using it as well.

With the selection narrowed to four genes, they tried again with a less stem-cell-like starting material -- fetal fibroblasts (basically, skin-forming cells). Once again, the loaded lentivirus was used to successfully convert these non-stem-cells into stem-cell-like cells. These product cells once again looked like embryonic stem cells, seem to have the right disposition of genetic material, and have been humming along for weeks and weeks now without problems (normally, the fibroblast cultures peter out as the cells can only divide twenty or so times before running out of steam).

Finally, they moved on to post-natal cells, and tried again with fibroblasts derived from foreskin (a ready supply of skin-forming cells, as it happens). Once again, the four genes were able to convert these to apparent stem cells. Notably, unlike the first two types of cells, these post-natal-derived cells did not all have the same behavior -- some of them kept differentiating into neural cells, whereas others kept differentiating into epithelial cells. This little quirk of behavior will be discussed in the punchline.

The overall upshot of this work is that Junying Ju and collaborators have found a remarkably small set of genes that appear to be able to "revert" certain kinds of body cells back into stem cells. There are some important caveats:

• The lentivirus approach can't be used as-is in the clinic. The weird variations they saw in the last experimental group probably come down to the lentivirus picking different areas to stick itself in the target genome. This can cause problems because it can disrupt normal expression of genes that are already there. This has actually caused cancer in at least one earlier gene therapy trial.
• It's not clear how to intentionally make the cells be not stem cells. Having these four genes cranked all the way on means that once you've converted a cell into a stem cell, it's still receiving a strong and continuous "be a stem cell" message. Part of the natural cell development process involves turning these signals off so that you can be an actual body cell. This is doable, but it's one more way that this is not an immediate replacement for natural stem cells (that will just do this themselves, with appropriate prompting).
• Finally, these cells just haven't been around that long. As the researchers themselves note, "...further work is needed to determine if human iPS [induced pluripotent stem] cells differ in clinically significant ways from ES cells."

One of the exciting upshots of this work that has not received much attention is what a great opportunity this is to learn about the natural process of cells being pluripotent or focusing on a specific function. It is fascinating, if perhaps not strictly surprising, that the process mostly comes down to a handful of genes. Knowing this kind of thing can help in our understanding of normal development and in helping to understand and perhaps prevent developmental (birth) defects.

I just ran into this in the annotated genome of Mycobacterium tuberculosis H37Rv:

3187030..3187611
/gene="mpt70"
/locus_tag="Rv2875"
/function="NOT REALLY KNOWN."

Someone at the Sanger Institute has a sense of humor, I think.

(For a little more information, the product of this gene is a protein known as Mpt70. Although the function of Mpt70 is unknown, it is an immunogenic protein, meaning that your immune system kicks up a fuss when exposed to it. This usually means it does something important, so we can be assured that people are studying it.)

One of the neat consequences of modern biological tools is the ability to dissect human ancestry via genetics. In particular, by tracing markers on mitochondrial DNA and Y chromosomes, we can gain a general understanding of how human populations have spread and intermixed, as well as getting a window into how that process has operated in a gender-specific manner.

In their recent paper The Peopling of Korea Revealed by Analyses of Mitochondrial DNA and Y-Chromosomal Markers, Jin, Tyler-Smith, and Kim look at mitochondrial DNA and a specific region on Y chromosomes in members of a number of Asian populations (Korean, Korean-Chinese, Mongolian, Manchurian, Han, Vietnamese, and Thai).

You can head over to the paper for details, but the upshot is that the the mitochondrial DNA evidence supports the idea of the Korean peninsula being populated largely by northeast Asians. This makes geographical sense:

View Larger Map

Note that the portion of modern-day China between Mongolia and Korea was previously Korean territory, and still contains a high percentage of ethnic Koreans living in China (see Korean-Chinese in the population groups above).

Notably, the Y-chromosome region examined shows a considerable bias toward Southeast Asian populations. The authors suggest that this is coincident with the spread of rice agriculture into the area, as that proceeded from the southeast.

Overall, this doesn't shatter any ideas about Korean ancestry -- basically, they came from that swath of land that is now Mongolia and the Russian far east. However, it's interesting to see the influence of rice agriculture on the genetic composition of the population. One imagines young men of southeast Asia making their way up the modern Chinese coast, passing on their farming practices and their genes through generations until both arrived in the peninsula.

Although these days the nice gentleman at Hankook market do it for me, I've had the occasion in prior years to clean squid for cooking. Beyond clearing out the intestines and the beak, you want to remove the ink -- ideally without getting it all over you -- and pull out the pen, that remnant internal shell that the squid uses as a sort of faux spine.

Over in their article Preparing the Perfect Cuttlefish Meal: Complex Prey Handling by Dolphins, Finn, Tregenza, and Norman tell us how an Indo-Pacific bottlenose dolphin does nearly the same job.

The researchers captured underwater footage of a female dolphin carrying out food prep on a cuttlefish. Briefly, the dolphin smacks the cuttlefish against the seabed, then knocks the dead cuttlefish around for a while to clear all the ink out, then scrapes it against the seabed again to remove the cuttlebone -- the equivalent of a squid's pen.

Why do all of this? Well, we can assume that the dolphin doesn't like inky, bony food, but in pure nutritional terms, the dolphin avoids unwanted pigments in the ink that can disrupt digestion, as well as avoiding having to crunch its way through the cuttlebone. I'll let the authors supply the punchline to the whole paper, as I think they've captured what's really exciting about this:

This behaviour is a dramatic example of how dolphins, with their relatively unspecialised morphology, can utilise behavioural flexibility to tackle prey items that require substantial handling before consumption.

Sounds like us, yeah?

In science, generally, your work is meant to be subject to peer review. This initially happens in the formal sense, as work is submitted to a journal. The journal's editor will send your manuscript out to others in the field, who will offer critiques and advice on the value of the work and the validity of the science. Research is then subject to - often passively, as others try to build on your work - additional peer review in the form of other studies carried out by other labs. After all, if your work has value, it's only natural for others to want to begin their studies where your research ended.

In their journal article Putative Nanobacteria Represent Physiological Remnants and Culture By-Products of Normal Calcium Homeostasis, Young et al address the issue of "nanobacteria," putative microorganisms that are smaller than any well-defined bacteria, can be cultured from human samples, and which have been suggested as causative agents behind a number of pathologies.

Notably, they had not been well-characterized in terms of what we might usually look for in a bacterium these days - DNA, RNA, proteins, and so forth. To date, they'd been identified as having a few characteristic protein bands, and some calcium and such.

This paper very thoroughly approaches the topic of nanobacteria, and comes up with some important observations. Summarized very briefly (this is a 35-page research paper), these are:

• Things that look like nanobacteria can be generated using ion and protein mixtures
• Serum actually slows this process down (which would explain why serum-identified "nanobacteria" take much longer to grow then the nanobacteria-like particles (NLPs) described above
• NLPs and putative nanobacteria look the same
• Proteins associated with nanobacteria appear to come from the serum it is "passaged" through
• These proteins are, in fact, from the serum
• Antibodies that are supposed to be against nanobacteria react with these serum proteins

I'll reiterate that this is the super-condensed, high-speed summary of a very detailed and thorough paper.

That last point about the antibodies is particularly important, as other groups had been applying those antibodies to diseased human tissues and saying, in effect, "Look, there are nanobacteria here! Maybe they caused this condition." By pointing out the massive cross-reactivity between these antibodies and known serum proteins, Young et al give a warning that what was probably happening was simply the detection of human proteins in humans.

Overall, this paper paints the picture of the putative nanobacteria as not being living organisms at all, but, rather, collections of calcium compounds stuck together with proteins. Although these could possibly be involved in some pathologies, they may also represent weird artifacts or possibly normal calcium-clearing mechanisms in the body. Regardless, it's important to know that they aren't bacteria, as that changes the way we'll think about them, whether they're a natural mechanism or a source of pathology.

My "wow" numbers for the week come from a talk about the Washington University Genome Sequencing Center.

Expansion rate of their data center: 646 GB/day

Note that this is the rate at which they are adding storage, not the rate at which they're adding data. They actually maintain their primary sequencing files, which are 2-3 terabytes a pop, for only a week. So this is just the storage they need to add to keep up with their increasing data collection rate.

Time to do a single sequencing pass on a human genome...

...using their Sanger machines: 14 days
...using their 454 machines: 11 hours
...using their Illumina machines: 1.3 hours

Time to do a single sequencing pass on an E. coli genome...

...using their Sanger machines: 30 minutes
...using their 454 machines: 1 minute
...using their Illumina machines: 7 seconds

This is a crow eating a squirrel.

Seen on the walk to work today.

Back when I was in grad school, a group at UCSD was exploring the genetics of Argentine ants in California, comparing their genetic markers with their behavior when paired. They discovered that California is basically ruled by one Argentine ant supercolony, where all the ants are relatives and thus there is no internal competition between Argentine ants.

The image of a statewide supercolony was always very striking to me.

Now, Sunamura et al have extended this kind of analysis in this paper, which you can find neatly summarized in this BBC article. Their discovery?

But whenever ants from the main European and Californian super-colonies and those from the largest colony in Japan came into contact, they acted as if they were old friends.

In short, they acted as if they all belonged to the same colony, despite living on different continents separated by vast oceans.

So, it's not the Californian supercolony; it's the Californian/Mediterranean/Japanese supercolony.

Impressive.

Want to make a low-cost laminar flow chamber, perhaps for some light microscopy work? Check out the snappily named Fast Benchtop Fabrication of Laminar Flow Chambers for Advanced Microscopy Techniques by David S. Courson and Ronald S. Rock of the University of Chicago.

They describe a straightforward method for handbuilding a chemically inert, reusable laminar flow chamber in about an hour. I'm not currently in a position to need a laminar flow chamber, but this is a nice set of directions for anyone who might want to do some microfluidics work without having to go to a machine shop for expensive, custom-made flow assemblies.

In a paper published this month in PLoS One, Elise Nowbahari, Alexandra Scohier, Jean-Luc Durand, and Karen L. Hollis reveal some exciting work in an oddly under-studied area - rescue behavior in animals. Humans clearly engage in rescue behavior, often to our own detriment, and we make complex decisions about whom we choose to try and rescue. You'd rescue your own kid. Would you try to rescue a cousin? A neighbor? A total stranger?

In this work, ants of the species Cataglyphis cursor were faced with a series of potential rescue situations, including:

• A trapped Cataglyphis cursor from their own colony
• A trapped Cataglyphis cursor from another colony
• A trapped ant from another species
• A trapped prey animal
• A trapped Cataglyphis cursor from their colony, chilled into inactivity
• No trapped animals

The results were quite specific: The ants only attempt to rescue active members of their own colony. They do this by digging away at surrounding sand, tugging on limbs (but not antennae!), and biting at the nylon snare trapping the ants.

This is fascinating work that brings up even more exciting future directions for research. As the authors conclude:

In sum, our findings establish that, in Cataglyphis cursor, rescue behavior not only is directed exclusively toward nestmates but also the nestmate must be active. Thus, rescue behavior necessarily depends on some form of actively produced eliciting stimulus, already known to be a pheromone in several ant species but one that contains a component unique to each colony.

What is the "help me" signal? Is that snare biting highly specific, or part of a general clearing of foreign matter from the problem area? How complex (versus, say, programmed) is this behavior?

I've also reposted their supporting videos to YouTube under PLoS One's Creative Commons license. They're worth a look:

You can read the original article by clicking here.

You're looking at a mobile phone fitted with an adapter that turns it into a microscope capable of light and fluorescent microscopy, able to resolve cells and microbes, that can be used to carry out field evaluations of malaria, TB, and other conditions that would normally require expensive lab equipment that third-world regions may not have access to.

In their article Mobile Phone Based Clinical Microscopy for Global Health Applications, Breslaur et al have leveraged the ubiquity of mobile phones across the world, including the third world, to provide an invaluable health care tool for areas that desperately need it. In this work, they use their mobile-adapting microscope to identify malaria, tuberculosis, and sickle-cell anemia, including the use of automated image processing:

In addition to the capture and transmission of data, the fact that mobile phones are essentially embedded computer systems offers the opportunity for significant post-processing of images. To demonstrate the diagnostic potential of image processing in this application, we carried out automated bacillus counting of the fluorescent TB images.

This is an impressive development that hopefully will be put into production quite rapidly. As comments already present on the article note, this is important as a public health development for much of the world and it promises to be a pretty cool device for biology hobbyists, too.

The article:

Breslauer DN, Maamari RN, Switz NA, Lam WA, Fletcher DA (2009) Mobile Phone Based Clinical Microscopy for Global Health Applications. PLoS ONE 4(7): e6320. doi:10.1371/journal.pone.0006320