Biology
Taking lab mice out of the lab to address a very serious question
When we think about research animals being returned to a life outside their lab cages, it’s often primates, dogs, or other large animals. But what happens when you free animals that have not only lived their whole lives inside a lab, but so did their parents, and their parents, and their parents stretching back for generations? Carolyn Beans at the Proceedings of the National Academy of Sciences takes a look at an experiment testing exactly that:
It was hardly a trek into the wilderness. The 90 mice were fenced into pens, with feeding stations providing all the mouse chow they could eat and aluminum pie plates dangling over their heads to deter passing hawks. Still, it was a world away from their former home in the laboratory of Andrea Graham, an ecological and evolutionary immunologist at Princeton University. These mice could now roam around an area of roughly 180 square meters, feeling the dirt under their feet and rain on their backs.
This may seem like something of a fun little bit of frivolity, but there’s a very important question behind this experiment. Researchers are highly dependent on laboratory mice as models for everything from aging and disease to treatments and even exercise and stress reactions in humans. But how much does the laboratory part of that combination shape the results? The idea of having extremely similar mice held in extremely similar conditions has been to eliminate as many of the variables as possible between experiments. But having mice live in what amounts to a clean-room environment isn’t exactly natural for them, and it’s not as if the humans treated with drugs or other therapies first modeled on these mice are going to spend their lives with no outside contact, running on sanitized metal wheels.
Is keeping mice in such controlled conditions making them significantly less effective as a model for how disease and treatments will work for people?
If the natural environment of a mouse—or a human—is itself a major factor affecting a disease or its treatment, studying it under strict lab conditions could skew the results. As pressure mounts for scientists to make mouse findings translatable to humans, a small but growing number of researchers are designing studies that use more natural experimental conditions. Their aim is not to replace traditional lab studies but rather to complement them with real-world context.
Andrea Graham, the researcher who set free her mice, was looking particularly at treatments for parasitic infections of nematodes. The mice she used were supposed to be “nematode resistant” and that certainly appeared to be true in the lab. But after a few weeks in the wild, where there were a variety of actual nematodes, her mice were harboring “massive infections.” The lab-based immunity did not hold in real world conditions.
Mice are still the human stand-in of choice in biomedicine. The vast majority of their genes have a counterpart with the same function in humans, and they suffer from many of the same diseases. …
Yet most successful therapeutic treatments in mice do not translate successfully into humans.
Researchers have argued for years over the standard conditions used for mice. Too cool? Too stressful? Not stressful enough? But maybe what’s needed is standard conditions that are less standard, more varied, and more natural. That may make it harder to eliminate all the variables in an experiment — but it could also yield results that have meaning beyond just “works on white mice in extremely controlled conditions.”
Okay, come on in. Let’s read more science!
Medicine and Health
The effects of LSD on someone born blind
When we think about an LSD “trip,” or the effects of any psychedelic drug, it’s hard not to think of them as … psychedelic. Full of glowing images, startling textures, and animated escapees from a Yellow Submarine. But what effect does LSD have on someone with no visual references? There are still hallucinations, they’re just hallucinations of other senses.
This case report offers rare insights into crossmodal responses to psychedelic drug use in a congenitally blind (CB) individual as a form of synthetic synesthesia. BP's personal experience provides us with a unique report on the psychological and sensory alterations induced by hallucinogenic drugs, including an account of the absence of visual hallucinations, and a compelling look at the relationship between LSD induced synesthesia and crossmodal correspondences.
Synesthesia is also one of those words that tends to be associated with vision. People experiencing synesthesia “hear colors” or “taste shapes.” But the person in this study, whose code name is Blue Polygon (taken from his favorite “brand” of LSD) reported synesthesia of a different sort. Under the influence of LSD, he felt as if certain music had plunged him under a waterfall. And where a sighted person might perceive the world in a cartoonish manner, Mr. Polygon had a similar touch experience in which everything felt slick, soft, and velvety.
The one thing that BP did not experience was anything he perceived as a visual phenomena.
A new class of drugs that seems to stop MRSA
Antibiotic resistant staph infections are one of the horror stories of our age — not only do tales of MRSA infection often come with gruesome results, but they remind us of how the flow of new antibiotics has slowed even as resistance to existing antibiotics becomes ever more widespread. And the fact that these infections often strike people who have been hospitalized for some other condition only makes them more frightening and difficult to fight off.
But a group of scientists who set out to study the lipid layer of gram-positive bacteria seem to have come across new members of an existing class of compounds that hit MRSA and similar infections from a brand new direction.
Here we used a Caenorhabditis elegans–MRSA infection screen6 to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection.
The indication here is that not only are these drugs effective against gram-positive bacteria, it’s going to be darn tough for the bacteria to develop resistance, because the drug disrupts a basic part of the bacteria’s structure.
With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.
But this is an early announcement — laboratory work. Don’t expect to see these drugs available in your hospital for years, and that’s assuming they don’t turn out to have effects that are disruptive to some part of our own biology when they reach trials.
Gut bacteria and drugs that are not antibiotics
It’s only in the last decade that we’ve really started to appreciate just what an effect gut bacteria can have on human health. While it’s long been recognized recognized that antibiotics can wipe out many different kinds of “good” bacteria in the gut, generating effects that linger long after patients stop taking the drugs, this study from the European Molecular Biology Laboratory, shows that other classes of drugs can also have a big impact on our friendly neighborhood biota.
One factor that showed up was that some drugs, though not intended as antibiotics, trigger some of the same mechanisms as antibiotics.
Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. … The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration.
So drugs we’re taking for other reasons might be reducing the effectiveness of antibiotics when they’re needed — as well as causing more fits for our resident helpers.
Recessions are bad for America’s health
A UCLA team looked at the effect of the Great Recession on Americans, and found that it was present in a lot of places other than their pocketbooks.
Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. …. significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).
This is a big deal. Not just a big deal for today’s science column — but a big deal for the core mission of this site: Putting more progressive politicians in office.
This paper is showing that the economic effect of the Great Recession had a directly measurable impact on American health. It had an impact because some people felt the direct effects of stress, such as elevated blood pressure. It also had an impact because some people felt a secondary effect, such as not taking their prescribed medications due to reduced ability to pay. It also shows that the people most affected by these changes were younger workers who suffered a job loss and homeowners whose equity (or homes) were stripped away by the drop in housing prices.
And, of huge importance, it shows that those Americans who were on Medicare or Social Security were to a much greater degree sheltered from both the direct and secondary health effects of the recession. Those on Medicare kept their medications. Those on Social Security did not lose their incomes. They, like most Americans, likely lost a significant amount of home equity, but they were buffered from the wild swingin the economy by exactly those programs designed to buffer them from wild swings in the economy.
For workers who did not have such protections, and were dependent on employer-sponsored healthcare or personally purchased healthcare at a time when incomes were stressed, there were lingering health effects. Which also has a cost.
Anthropology
Did Stone-Age farmers cause deforestation in Africa?
Deforestation is one of those problems we generally think about as a modern issue. Sure, ancient peoples in Australia were possibly tending some right-large fires more than 10,000 years ago, but for the most part, we don’t think about stone-age peoples as having all that great an impact on their environment. Except … think again. In Africa, large swatches of what had been rainforest became more open grasslands, and quite possibly not because there was a change in climate.
There is evidence for a period of major forest loss between 3,000 and 2,000 y ago [termed the Late Holocene rainforest crisis (LHRC)]. Attributing the cause of this decline is complicated by the fact that this period coincided with major expansion of Neolithic and early Iron Age farmers southward from the Nigeria/Cameroon border regions into western Central Africa. Did the farmers take advantage of a forest retreat driven by climate drying, or were they the primary cause of the forest loss? In recent years, there has been a vigorous debate on the cause of the LHRC. Now, Garcin et al. provide new data and an unexpected new insight, presenting strong evidence that there was no strong drying event, and therefore suggesting that it was direct deforestation that caused this retreat of the Central African rainforests.
The evidence for that rainforest decline had been visible to scientist for decades, but they had attributed it to some shift in weather patterns that caused a drying of the continent’s interior. Now it seems the evidence uncovered by a French and German team points to many hands, holding many stone axes.
A 10,500-y sedimentary record from Lake Barombi, Southwest Cameroon, demonstrates that the rainforest crisis was not associated with any significant hydrological change. Based on a detailed investigation of a regional archaeological database, we present evidence that humans altered the rainforest ecosystem and left detectable traces in the sediments deposited in Lake Barombi.
Humans took over the task of spreading plants, after we killed off the megafauna
Many plants, particularly those that produce fruit, depend on animals to spread their seeds to new areas. In both the Americas and Europe, there were historically a number of types of animals — from horses to rhinos to elephants — available to carry out this role. But then … we killed them. Or at least, humans made a contribution to the decline and extinction of many species which may have already been under stress from other factors. They may have been standing on the edge, then we pushed.
Then we took over part of their job.
We quantified the human role in modifying distribution ranges of Neotropical fruit species by comparing the distribution of fruit species that have been part of both human and megafauna diets with fruit species that were exclusively part of megafauna diets. Our results show that human food usage has expanded the distribution of species that would otherwise have suffered range contraction after extinction of megafauna. Our analyses help in identifying range segments of fruit species that may hold key genetic diversity to sustain food systems and to maintain critical ecosystem functions.
Paleolithic hunter gathers taketh away large hairy animals, paleolithic hunter gatherers giveth fruit.
Metascience
Scoring the impact of important papers
Some scientific papers make a big splash in the media. For example, anything related to the human diet is likely to get wildly out-sized attention relative to it’s long-term importance. Other papers that turn out to be seminal works draw few, if any, headlines outside of rarefied journals. In chemistry, genetics, geology — in every field — many of the critical, game-changing works weren’t recognized for years or decades after their publications. But still, scientists are often measured simply on how often they publish and how often they get cited by others.
Instead of trying to determine the underlying importance of works, too many institutions and universities work on a “publish or perish” model that values quantity over … everything. So how about a system that measures the importance of works by looking at their downstream impact on subsequent publications?
Citation counts exhibit preferential attachment and follow a rigid “news cycle” that can miss sustained and indirect forms of influence. Building on dynamic topic models that track distributional shifts in discourse over time, we introduce a variant that incorporates features, such as authorship, affiliation, and publication venue, to assess how these contexts interact with content to shape future scholarship. We perform in-depth analyses on collections of physics research (500,000 abstracts; 102 years) and scholarship generally (JSTOR repository: 2 million full-text articles; 130 years). Our measure of document influence helps predict citations and shows how outcomes, such as winning a Nobel Prize or affiliation with a highly ranked institution, boost influence.
The research shows that scientists who simply hang around a field for a long time end up with, not surprisingly, a lot of citations, even if their work is less than ground-breaking. This gives them a perceived authority. Researchers who introduce genuinely critical ideas are often given little credit for the change in discourse caused by their work.
Changing the way schools and researchers “credit” their colleagues is something that should be done, if only to spare those engaged in substantial long-term research from having to step onto the paper treadmill at regular intervals to “prove” their worth. But setting free the mice is going to be a lot easier for researchers than changing the way they keep score of their careers.
Sustainability Science
Where we live is making both our homes and the wilderness more likely to burn
There’s no doubt that changes in climate have played into recent disasters. Whether it’s wildfires or mud slides, the impact of more severe, or severely altered, weather patterns are having an effect that can be measured in acres devastated and lives lost. But problems are often compounded by choices we’re making that are even more direct than human impact on the climate.
When houses are built close to forests or other types of natural vegetation, they pose two problems related to wildfires. First, there will be more wildfires due to human ignitions. Second, wildfires that occur will pose a greater risk to lives and homes, they will be hard to fight, and letting natural fires burn becomes impossible. We examined the number of houses that have been built since 1990 in the United States in or near natural vegetation, in an area known as the wildland-urban interface (WUI), and found that a large number of houses have been built there. Approximately one in three houses and one in ten hectares are now in the WUI. These WUI growth trends will exacerbate wildfire problems in the future.
A third of all American homes border on areas of natural vegetation. That sprawl creates a huge interface between people and wilderness that is bad for both.
AstRonomy
Missing dark matter helps confirm the existence of … dark matter
You’re going to miss me when I’m gone. This certainly appears to be true where “you” equals astrophysicists and “I” equals dark matter.
Warning, math and obscure terminology ahead.
Studies of galaxy surveys in the context of the cold dark matter paradigm have shown that the mass of the dark matter halo and the total stellar mass are coupled through a function that varies smoothly with mass. Their average ratio Mhalo/Mstars has a minimum of about 30 for galaxies with stellar masses near that of the Milky Way (approximately 5 × 1010 solar masses) and increases both towards lower masses and towards higher masses. The scatter in this relation is not well known; it is generally thought to be less than a factor of two for massive galaxies but much larger for dwarf galaxies. Here we report the radial velocities of ten luminous globular-cluster-like objects in the ultra-diffuse galaxy NGC1052–DF2, which has a stellar mass of approximately 2 × 108 solar masses. We infer that its velocity dispersion is less than 10.5 kilometres per second with 90 per cent confidence, and we determine from this that its total mass within a radius of 7.6 kiloparsecs is less than 3.4 × 108 solar masses. This implies that the ratio Mhalo/Mstars is of order unity (and consistent with zero), a factor of at least 400 lower than expected. NGC1052–DF2 demonstrates that dark matter is not always coupled with baryonic matter on galactic scales.
If you didn’t get that on first reading (where “you” equals … you) then join the club. But basically it says that astronomers have long been able to determine that there’s a lot of missing mass out there — or at least some unseen source of gravity. For most galaxies, this missing mass is hundreds of times greater than the visible mass. That’s the dark matter.
But the way stars are moving around in galaxy NGC1052–DF2, suggests that there’s not even twice as much stuff there as what we can clearly see. Very little dark matter compared to other galaxies. For now, there seems to be no good idea on why there should be so little dark matter in this particular galaxy, but the mere fact that there are galaxies out there with less than expected dark matter goes a long way to proving that dark matter is not just some previously unknown quality of how space behaves in the presence of a large amount of visible matter and is in fact … something that can be missed.
Another warning: Some Saturday I’m going to subject all of you to a full-bore presentation of my pet theory that dark matter does not exist in this universe, but is in fact the result of gravitational leakage across universe boundaries in the form of membrane distortions resulting from statistical accumulations of visible matter in an infinite multiverse. My pet theory still works for this dark matter-free galaxy and for some other tricksy phenomena, as well. And I will explain it using nothing but a stack of paper and Newtonian math … because I got a C in Calculus and am not capable of doing math in higher dimensions. Come to that, I got a C in plain old algebra. It’ll be a very simple explanation.
Infographic
As usual, this week’s image comes from Andy Brunning at Compound Interest. You can find a larger, easier to read version of the image at Andy’s site.