Category: bio


Wonderous Stories

Science is sometimes criticized as draining the meaning and beauty out of existence, when in reality it has the opposite problem.

Because it allows one to acquire knowledge otherwise inaccessible to common perception, science gives us access to a whole other landscape, with terrifying and beautiful scenery. It is hard to discuss the history of earth through deep time without falling into epic geopoetry: an oxygen catastrophe so intense the oceans rusted; the sudden diversification of life at the beginning of the Cambrian; the collapse of a habitable Antarctica with the opening of the Drake passage and the start of the circumpolar currents.

I’m going to share a few of the stranger creatures that live in this landscape, or the glimpses that we’ve gotten of them through the haze. They are horrifying, but beautiful, and I think that they make us look at everyday things in new, challenging ways.

“He spoke of lands not far
nor lands they were in his mind.
Of fusion captured high
where reason captured his time.”

Life on land is hard. It’s dry, for one thing; a lot of evolutionary engineering goes into maintaining moisture, and it’s irradiated by ultraviolet light. It’s a really interesting story how complex life spread to the land, but one of the creepier chapters is the evolution of land plants. Did early algae just throw themselves on the beach, slowly evolving in intermediate environments? Some scientists have theorized that something more interesting was happening on those primordial shores.

More than 90% of plants are mycorhizal. That is to say, they have fungal symbiotes in their root systems. These associations are ancient; fossils in the Rhynie cherts show that they were around 400 million years ago. And they’re weird. For one thing, the fungi can siphon off nutrients from the host plant, then feed them to other plants which get their nutrition solely through this exchange.  They also probably play a role in gathering mineral nutrition from the soil for their host plant. Some associations are obligate and very specific; this is why orchids can be difficult to grow.

monotropa in da house

Indian pipes (monotropa) are shown here poking out of the forest floor. They feed exclusively off of a mycorrhizal network which exchanges nutrients with surrounding trees.

What if land plants, what we think of as single organisms, are actually so closely associated with fungi as to be considered partly compose of fungus? That’s the basic idea of the fungal fusion hypothesis. Working together, the fungus and the alga would have been better able to move onto land than either individually. For example, the fungus could have extracted mineral nutrition to the benefit of the alga, while the photosynthetic alga provided food, or compounds to screen the two of them from UV light. Mycorhizal interactions create oily substances in modern plants which protect them from drying out; such an interaction could have protected an early land plant from desiccation as well.

It may have been that land plants were merely an association of fungi and algae, essentially overgrown, vascularized lichens. “Mycotrophism made terrestrial plant life possible,” writes (Pirozynski and Malloch 1975). But it may have been more intimate. Living together, the fungi may well have become an endosymbiont, living inside of the algal cells. Over time, this relationship could have been restructured, fusing fungal genes into a single consolidated genome. Land plants could well be a remix of preexisting creatures. Its not the first such endosymbiosis; chloroplasts and mitochondria arrived on the scene the same way.

 
Pirozynski KA, & Malloch DW (1975). The origin of land plants: a matter of mycotrophism. Bio Systems, 6 (3), 153-64 PMID: 1120179
 
Jorgensen R (1993). The origin of land plants: a union of alga and fungus advanced by flavonoids? Bio Systems, 31 (2-3), 193-207 PMID: 8155852
 

“…It is no lie I can see deeply into the future.
Imagine everything
You’re close
And were you there to stand
So cautiously at first and then so high….

What is cancer?

Usually, the answer is that it’s cells which have gone on a solo career. They consume the body’s resource and produce nothing useful to the organism, only more of themselves. They are selfishness personified. But there are anomalies which this simplistic account doesn’t explain. For example, why would selfish cancer cells cooperate with one another in tumor formation?

A cancer cell. Click for source.

A longstanding criticism of cancer biology and oncology research is that it has so far taken little account of evolutionary biology,” write (Davies & Lineweaver 2011). They’ve taken a new look through an evolutionary lens and come to the conclusion that cancer is an atavism.

Atavisms are regressions to a more primitive evolutionary states. For example, birds are evolutionarily derived from reptiles with teeth, but do not have teeth themselves. Usually. In rare cases, those ancestral reptilian genes are reactivated, and a bird with teeth will result. That’s an atavism. The notion which these researchers propose is that cancer is an evolutionarily primitive state which emerges when cells are damaged by chemicals, radiation, or time.

The evolution of multicellular life, they propose, required a robust toolkit of cellular communication pathways in order for individuals to cooperate first as a loosely knit colonies with basic division of labor. These tumor-like growths, the first steps toward multicellular life, are what the authors call “Metazoa 1.0“. On top of this basic genetic framework for the self-organization of cells there evolved a further regulatory network responsible for the complex organization of Metazoa 2.0 like us. It’s this delicate regulatory network which goes awry in cancer. At that point, the ancient toolkit is activated and the atavistic mode kicks in.

If true, this framework is a hopeful one. Conventionally, the impressive arsenal of skills available to cancer has been explained as evolutionary adaptations, fed by the cells’ high rate of growth and mutation. This would mean that its arsenal is open-ended, able to evolve dynamically in response to therapy. But if it’s an atavism, though, its toolkit is a finite set limited by what was available to metazoa 1.0.

 
Davies, P. C. W.,, & Lineweaver, C. H (2011). Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors Physical Biology, 8 (1) DOI: 10.1088/1478-3975/8/1/015001
 

 

“Sound did silence me
leaving no trace.
I beg to leave,
to hear your wonderous stories.”

It’s one thing to find unsettling fossils in the genomes of plants, or in pathologies. It would be something else entirely if there was something strange and beautiful lurking deep inside ourselves.

The human genome is littered with dead viruses. It starts with a retrovirus, something like HIV maybe. It reproduces by inserting its genes into its host’s DNA, where they get expressed by the cell’s transcription/translation machinery. Most of these cells die with the host, but every now and then a germ line cell gets infected, a sperm or egg. This viral hitchhiker then gets passed on to the organism’s progeny. Over time, they’re usually inactivated by mutations, or actively silenced, but they pile up. 8% of the human genome is composed of dead viruses.

syncytin

The structure of syncytin, a retrovirus protein which has been recycled in the human genome. Image source from Renard et a 2005; click for link.

It gets weirder. Meet syncytin; it’s a protein which is involved in placental formation in humans. It’s also part of an ancient, repurposed viral gene. Not only was this virus integrated into our genomes, it was rebuilt into an essential part of the mammalian life cycle. It’s happened several times, too: mouse syncytin is derived from a different viral infection than primate syncytin. Experiments on mice show that without this gene, the placenta misforms. Another retrovirus is involved in placenta formation in sheep.

Apparently, mammals across the evolutionary tree have been independently infected by retroviruses, incorporated those viruses into their genomes, and specifically put them to work building placentas. Did these particular viruses just happen to carry genes preadapted for placental formation? Or did mammals evolve and diversify as a result of viral genes flowing into their genomes? What other key biological pathways used to be free-floating viruses?

 
Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr, & McCoy JM (2000). Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature, 403 (6771), 785-9 PMID: 10693809
 

 Dupressoir, A.,, Vernochet, C.,, Bawa, O.,, Harper, F.,, Pierron, G.,, Opolon, P.,, & Heidmann, T. (2009). Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. Proceedings of the National Academy of Sciences of the United States of America, 106 (9) DOI: 10.1073/pnas.0902925106

There is a companion article exploring the issue from the perspective of environmental monitoring over at ArkFab.

Human influence on the environment has increased dramatically over the last 10,000 years, to the point that some geologists have argued that human reworking of the earth defines a new geologic age, The Anthropocene. (Zalasiewicz et al, 2008) Much of the focus has been on relatively robust, tangible changes in biogeochemistry. Examples include:

  • megafaunal extinction, accelerated erosion (Zalasiewicz et al, 2008) and nitrogen fixation resulting from the spread of intensive subsistence patterns
  • the loss of stratospheric ozone resulting from the release of novel chlorofluorocarbons

However, fleeting and less tangible effects are also important. Two examples are:

  • the light pollution resulting from urbanization and transportation infrastructure
  • changes in the acoustic environment resulting from direct addition of sonic energy and memes, as well as indirect sources.

A year-long composite view of the earth at night, showing human light generation. White lights are cities; blue lights are fishing boats; green lights are natural gas flares, and red lights are ‘ephemeral light sources’, interpreted as fires. Image from  NOAA National Geophysical Data Center – click for source + discussion.

Light pollution, the scourge of urban astronomers, is a well-accepted phenomenon with serious consequences. A 2004 review begins:

In the past century, the extent and intensity of artificial night lighting has increased such that it has substantial effects on the biology and ecology of species in the wild. We distinguish “astronomical light pollution”, which obscures the view of the night sky, from “ecological light pollution”, which alters natural light regimes in terrestrial and aquatic ecosystems. Some of the catastrophic consequences of light for certain taxonomic groups are well known, such as the deaths of migratory birds around tall lighted structures, and those of hatchling sea turtles disoriented by lights on their natal beaches. The more subtle influences of artificial night lighting on the behavior and community ecology of species are less well recognized, and constitute a new focus for research in ecology and a pressing conservation challenge. (Longcore & Rich 2004)

The amount of sonic energy released by human activity is recognized as an urban nuisance as well as an occupational safety concern. It also has recognized ecological effects: urban European robins have begun singing at night, when they have less acoustic competition. (Fuller et al 2007) Frogs have begun changing the pitch of their croaks in order to talk over traffic noise (Paris et al 2009)  In addition to sonic energy, human activity has released sonic memes into the environment. A meme is a self-replicating information pattern; jokes and computer viruses are two examples of memes. A person or computer acquires a meme and then spreads it, through retelling or infected emails. Sonic memes, such as ambulance sirens and cellphone ringtones, have been picked and repeated by songbirds. (Stover 2009) This is very interesting: human memes, the basis of Richard Dawkins’ ‘extended phenotype’ concept, have organically extended into other animals’ extended phenotype. (Recent reports of dolphins mimicking human speech are also very interesting in this context. The reverse flow also occurs, as animal communications are repackaged as ringtones or ambient music.)

Continue reading

Editor’s note: I am very busy and/or have major writer’s block. I am thus recycling my greater hits. Here we see a review of a review (a metareview if you will) of Ben Stein’s dawkumentary “Expelled”. The original review appeared in the Carolina Review. For those unfamiliar with CR (you blessed souls!), it is UNC-CH’s ” journal of conservative thought and opinion”. It is a perennial lulz-bucket, attributing climate change to solar forcings and/or Milankovich cycles, mangling ocean acidification, and wondering out loud, in public, why a 2008 paper was not included in the IPCC AR4 (published in 2007). They consider community reclamation of a long-standing eyesore to be a ‘hostile act‘ worthy of paramilitary response, citing the presence of ‘posters’. Here’s my response to one of their more abysmal publications. The article it responds to can be found here; my critique originally ran in CackalakConspiracy, back in a time when I still cared about typos.

Walker’s review, like Stein’s movie, is full of florid talk about “freedom”: freedom of speech, religion, science (the last ironic, for the creationist/intelligent design movement has done everything it can to prevent science from being taught in public schools). America has “an amazing record for upholding freedoms.” Stein rolls footage of Soviets and Nazis; Walker calls the dismantling of science and science education “a struggle against a great tyranny.”

But this talk of freedom is merely an emotional appeal. The speech of creationist “scientists” and ID advocates is not being squelched; it is just not taken seriously. For whatever successes creationism may have in philosophy or religion, it has failed as a science. This is why the mainstream rejects creationism for funding, publishing and inclusion in school curricula, not because of atheistic preconceptions. Film critic Roger Ebert drew this analogy: The final question on “Who Wants To Be A Millionaire” asks you for a scientific explanation for the patterning of life on Earth. You phone not just a friend, but the scientists of the world, who overwhelmingly advise you to choose (A) evolutionary biology. Yet you choose (B), intelligent design, and claim censorship upon being denied your millions. This is not an expulsion; it is a flunking.

Walker characterizes evolution and ID as rival “theories” in the “scientific community”. However, in science the word ‘theory’ does not mean a guess or an opinion the way it does in popular speech; it refers to an explanatory construct which is used to interpret data and to make predictions. By this standard, evolution wins hands down and ID falls flat on its face. Because any piece of data can be interpreted as evidence for a Designer (for example, by sufficiently muddying the proposed design goals), ID makes no predictions and no explanations (a “theory” that accommodates anything explains nothing). On the other hand, evolution makes several strong predictions about the world (the existence of a nested hierarchy of physical traits, for example.) ID is not a rival scientific theory; it is an attempt to inject religious propaganda into public education.

We don’t accept non-explanations elsewhere in science. Why should the origins and evolution of life on earth be different? Image from the internets….

Nor is evolution “all a question of faith,” a rival religion. It is purely descriptive, not perscriptive. It has no infalliable holy text; it has no ritual structure; it has no ineffable mystery. Though some may use it to bolster their religious beliefs like “renowned evolutionary biology [sic] and atheist Richard Dawkins,” the theory of evolution is no more a religion than the theory of gravity or relativity. Walker claims that “by definition and practice creationists and ID scientists are quite different”. This is incorrect, both because ID is not science and because it is accurately classified as a subset of creationism. Classical creationism and ID are both are antiscientific programs with thinly veiled religious agendas. They both negate accepted evolutionary biology, often along with other aspects of mainstream science such as molecular biology, genetics, and paleontology. Both reject “naturalism” in the scientific study of life, as though science was not based upon methodological naturalism to begin with. Both tend to blame various social ills on the theory of evolution, and erroneously infer from this that it is incorrect. Perhaps most tellingly, Expelled’s own publicity team advertised the movie as “Evolution vs creationism”.  Continue reading

A while back, we started looking at a poorly thought-out article from the website C3Headlines. C3 is starting to make a name for itself as a goldmine of climate comedy- their claims have recently been addressed at Tamino and SkepticalScience.

We’re going to keep digging into C3‘s claim that carbon dioxide concentrations have been increasing linearly over the 20th century. They seemed to draw this claim by eyeballing the graph of CO2 concentrations and qualitatively describing them as linear, apparently using the inset in their first figure to compare linear, quadratic, and exponential trends. This is a faulty method: it’s an elementary fact of calculus that ANY smooth curve, when viewed appropriately, will appear linear. The point has already been made but it’s worthwhile to keep looking because there are some interesting graphical follies at play; examining them further might help us understand how and why graphs are misunderstood.

Figure 1: From C3Headlines’ article on “The Left/Liberal Bizarro Anti-Science Hyperbole”, which claims that CO2 concentrations are increasing linearly. Click to read it, if you dare…

C3‘s second graph in this article measures the change in atmospheric CO2 by calculating a month-to-month percentage change. It’s not entirely clear why they are using a percent change, rather than the standard practice of expressing rate of change as concentration change per year (like the source of their data uses). Whereas ppm/year is an absolute measure, each datum generated by the percentage-change method depends strongly upon the value of the previous month. As a measure of long-term rate of change, it is a bit questionable.

My primary concern, though, is with their use of monthly data in the first place. In my last article, we noted that, without explanation, C3 confined their focus to January CO2 concentrations. Were they consistent, they’d also look at January rates of change – of course, doing so might lead to unacceptable conclusions.

 Figure 2. Rates of CO2 accumulation have been calculated for the month of January, consistent with earlier investigation of January CO2 concentration. Over the period of observation, rates have increased at a significant (P~0.0005) acceleration of 0.11 ppm/year^2. Monthly rates throughout this article have been calculated by considering the change in CO2 between adjacent months, and assuming that a month is 1/12 of a year. Interpolated values of CO2 were used to avoid annoying data holes early in the record.

Instead, they look at the rate of change for every single month on record. Why do I find that problematic? Well, let’s look at the full record, with monthly resolution: Continue reading

It is a lovely spring day and I am absorbing some sunlight, hanging out in the tail end of the Carrboro Really Free Market while I type up my notes on the Duke Mycology Symposium. [CLICK HERE FOR DAYS ONE AND TWO]

There were a couple of posters which really caught my eye. One thing that I think is very interesting about fungi is their symbiotic relationships with plants. So I was excited when I saw two posters, both put together by Ryoko Oono and colleauges: “Populations structure in Lophodermium spp., a common fungal endophyte of loblolly pine” and “Effcts of foliar fungal endophyte diversity on plant protection against pathogens”. The first presents some preliminary information about the distribution of Lophodermium amongst pine trees in North Carolina. They found that there are three distinct subgroups of the of the fungus, despite not being geographically isolated. This suggests that there is limited gene flow between the subgroups. The second poster discusses the ecological role of fungal symbiotes: both single and multiple fungal colonizations can increase pathogen resistance, and since individual fungi types antagonize specific pathogens, you might expect a diverse group of colonizers to repel the most pathogens. However, there may also be a sort of tragedy of the commons effect, in which the individual members of diverse group of symbiotes have no particular dedication to protecting the host plant. Clarifying these issues will require more research, and the poster outlines a plan for further study.

The biochemistry of metals was a recurring theme in this symposium. We’ve already looked at iron, nickel, and cobalt; so let’s wrap up our tour of the transition metals with “Copper homeostasis as a virulence factor in systemic infection by the human fungal pathogen Cryptococcus neoformans,” by Chen Ding and colleauges at Duke. They describe the susceptibility of Cryptococcus to copper toxicity in the host, and the role of a class of biomolecules called metallothionens in protecting Cryptococcus from the metal. Interestingly, they also present data showing that copper levels are elevated in the serum of Cryptococcus patients – evidence, perhaps, for the immune system incorporating copper into its chemical weaponry! This would be the exact opposite reaction that it has when it comes to iron, which it withholds in an attempt to starve pathogens of nutrients (Nesse and Williams 1994; p. 29-30)

Yeast colony macrostructure - photo from the Magwene Lab - click to visit them

Finally, there was “Genetics, genomics, and variation in yeast colony morphology”, presented by Josh Granek and colleagues at Duke. They studied the yeast saccharomyces cerevisiae under a variety of different growing conditions. They found that, under conditions of abundant nitrogen but scarce fermentable carbon, the yeast colonies developed complex, organized structures large enough to see with the naked eye. This sort of emergent behavior is very interesting; it shows the bottom-up organization of biology by which relatively simple units can have complex system-level behavior … and understanding how cells communicate and cooperate in a colony can provide insights to the transition from unicellularity to multicelluarity.

That’s all there is to say about the symposium. One thing that I have been thinking about is the involvement of mycology communities in doing environmental monitoring. Simple citizen science monitoring programs already exist for animals and plants (Cohn 2008). Why not monitor the third domain of eukaryotes? Mycological enthusiasts already have local clubs, and the data gathered could provide insights into fungal biogreography and ecological change.

Further Reading
Cohn, J. (2008). Citizen Science: Can Volunteers Do Real Research? BioScience, 58 (3) DOI: 10.1641/B580303

Randolph Nesse, & George Williams (1994). Why We Get Sick: The New Science of Darwinian Medicine. Vintage Books: New York

Mycology Symposium, Day 2

Day 2 of the Duke Mycology Symposium has wound to a close, [DAY 1 HERE] and I am sitting on my porch contemplating the afternoon’s lectures:

“Pathogen recombination during the amphibian Chytridiomycosis pandemic: Why change what’s working?”

A genetics perspective on Bd, a fungus responsible for widespread amphibian mortality. Apparently one of the factors in its spread is the abundance and transport of bullfrogs (raised for food) and xenopus frogs (used in medical research), which can carry the disease without being killed by it. The recent spread is caused by a single Bd strain which reproduces by cloning itself – it should therefor be genetically uniform. Yet, in practice Bd has a ‘dynamic genome’. This led to discussion led to mechanisms for genetic change without sex, such as mitotic crossover and gene conversion.

“Pathogenicity factors in the chytrid fungus and amphibian pathogen B. dendrobatidis”

Further discussion of Bd, this time from a molecular / genomic perspective. Perhaps the most interesting part was evidence that chytrids contain rhodopsin, a light-sensitive pigment. [] I was also alerted to the existence of the 1000 fungal genomes project.

“Pleiotropic roles of the UPR pathway in Cryptococcus”

UPR is the unfolded protein response – when there are bits of proteins floating around inside a cell, it’s a bad sign. Maybe those proteins were torn apart by heat, or a toxin. This talk looked at the responses of Cryptococcus to the presence of the UPRs. In some cases, they release ‘chaperones’, proteins which help other molecules assemble correctly. Or, they might release dedegredation enzymes to clean up the mess. In extreme cases, they may even trigger apoptosis, a sort of cellular suicide.

“The adaptive value of Flo11‐dependent flocculation and adhesion in yeast”

Epigenetics: Not just for woo-meisters! Click for sauce.

Proteins on the surface of certain yeast cells act  to let the cells stick together and form clusters, which then fall out of their liquid medium. The gene for this surface protein is under considerable epigenetic control – there was a really beautiful picture the speaker presented, in which genetically identical yeast cells nonetheless have different levels of gene expression. Additionally, this phenomenon is an example of the green beard effect.

“Fear the Titans: When bad yeast get worse”

Titan cells are variants of cryptococcus. as much as 20 times as large as typical cells. Continue reading

Mycology Symposium, Day 1

When I’m not too busy raging at skuptaloids online, I enjoy molecular biology and mycology, the study of fungi. Towards those ends, I’m visiting the Duke Symposium in Celebration of Mycology and Mycologists. I was only able to attend a few afternoon lectures on the first day of this conference, but am enjoying it greatly! Some of the lectures I attended:

“Glycoengineered yeast: from platform to product”

A completely qualitative assesment of the information storage in various biochemical media. You can see why I have a huge crush on glycans. Souce is "Emerging Glycomics Technologies" by Turnbull and Feild 2007; click for lynkz

Discussed the engineering considerations is convincing yeasts to produce biochemicals – for example, drugs. A major challenge is in glycosylation, the addition of complex sugars to proteins. Glycochemistry is very interesting to me; it is still very much a biochemical frontier.

“Membrane lipids and fungal virulence”

Glucosylceramides in fungi and humans are different, with fungal compounds featuring an unsaturated site and a methyl side group. Humans and fungi also have slightly different enzyme active sites to deal with these differences, suggesting that drugs can be developed to target the active sites in fungal pathogens without disrupting human biochemistry. The drug candidates discussed actually have analogs in commercial fungicides. Continue reading

i still exist!

Its true! Here I am!

So what is on the TopOc horizon for 2012?

  • More hard-hitting commentary!
  • More sassing of people who don’t understand graphs!
  • Updates on previous projects!
  • Audiovisual delights!
  • More sweet hax!
  • Fractals and fungaloids!
  • Pentagons and pentagrams!
  • More dry ice! (The shark puppet will also return.)

Here is a mushroom to tide you over while you wait…

It's like a fungal satellite dish!

TopOc is occupying Durham, for great win and/or lulz! One highlight on the horizon is a leet haxor skillshare – I want to show off the sweet alcohol stove I built! (via this video)

In the meantime, enjoy this pleasing image 🙂

Praying mantis.... or preying mantis??? Clearly the tyrannosaur of the insect world. Photo via Ildar Sagdejev; clix four phool.

Yay!

Antiscience campaigns often share the characteristic that they

A schematic of a climate model - By NOAA via WikiMedia Commons; click for sauce.

complain about the open questions, anomalies, and experimental limitations inscience. Scientists, on the other hand, work

hard to resolve these issues. Creationists complain about uncertainties on the chemical origins of life; biochemists generate and test hypotheses, developing useful technology and techniques in the process. (Bullard et al. 2006) A paper, championed by climate change skuptix, (eg, here) complains about the use of large flux corrections in climate models. (Soon et al. 2001) It was published a decade ago.

What was the state of computation back in 2001? There were no iPhones; cellphones still had hinges and were just starting to become controversial in schools. I didn’t see an iPod until late 2002, and for a long time it was just one person who had one*. We had just started trading AIM screen names instead of phone numbers. There was no Facebook, there was no Twitter, there was no YouTube. Xanga didn’t even appear on my radar until 2003. The Flash Revolution was in its infancy: StrongBad answered his first email in August 2001. It was, simply put, Peanut Butter Jelly Time.

Since then, while skuptix have done little more than whine, climatologists have been hard at work  improving climate models. It’s 2011 and climate models no longer use flux corrections. They still confirm the obvious: blankets are warm. More blankets are warmer.

* ❤ 😛

~~~—~~~

Bullard, T., Freudenthal, J., Avagyan, S., & Kahr, B. (2007). Test of Cairns-Smith’s ‘crystals-as-genes’ hypothesis Faraday Discussions, 136 DOI: 10.1039/b616612c

Soon, W., Baliunas, S., Idso, S., Kondratyev, K., & Posmentier, E. (2001). Modeling climatic effects of anthropogenic carbon dioxide emissions: unknowns and uncertainties Climate Research, 18, 259-275 DOI: 10.3354/cr018259