Sloth Skin: An Arborial Buffet

Calling someone a sloth (los peresosos, or “the lazies” in Spanish)  is not the way to begin a friendly conversation or a life-long friendship, although  these slow-moving animals are a source of constant wonder to biologists, ecologists — and should be to skin researchers. This post aims to elevate the sloth  to the same level of respect as the zebrafish, knock-in and knock-out mouse, and the fruit fly.


Twenty percent of the body mass of the sloth is comprised of hair and skin, and sloth nails are several inches long, resembling those of an alien from a faraway planet. The skin of the three-toed sloth (Bradypus spp) is a complex biological community, with about 100 pyralid moths (Cryptoses spp) per animal and a large mass of algae (Trichophilus spp) living on its hair. The current hypothesis is that the  moths digest  food  stuffs for the algae which grow hydroponically in grooves and hair crevices and form a food source for the sloth. When the sloth is  lazy (all the time) and bored of eating leaves, there is nothing like a good algal meal from its own hair garden for rounding out the diet. The sloth keeps this biosystem churning, an example of “biological mutualism,” by leaving the trees once a week to defecate and form a rich nest (using its vestigial tail as a spade) for  moth larvae. This is a dangerous proposition, because a predator can catch the sloth when it leaves the trees for its toilette. Life is not all rest and munching for the sloth, as it may become the early morning meal  for the harpy eagle, whose talons can lift it from the forest canopy.


The sloth certainly deserves respect for its complex and creative evolution — and for stimulating lots of biological research (Pauli et al, 2014)



Pauli JN, Mendoze JE, Steffan SA, et al A syndrome of mutualism reinforces the lifestyle of a sloth (2014) Proceedings of the Royal Society B,281:20133006



This work, accessed on wikipedia,  has been released into the public domain by its author, Tauchgurke.

Scleroderma and Cancer: Is Anti-Tumor Immunity the Missing Link?

by Guest Blogger John Varga MD, Northwestern University, Chicago, IL

Scleroderma, or systemic sclerosis, remains a mystery. The cause of this rare autoimmune disease is unknown, and genetics appears to play only a modest role. It has long been known that like dermatomyositis and other autoimmune disease, scleroderma coexists with cancer more often than would be expected. Could scleroderma in some cases arise as fallout from an anti-cancer immune response mounted against a nascent tumor?

This is the provocative hypothesis examined by Rosen and colleagues from Johns Hopkins in the January 10 issue of Science. Rosen et al observed that while cancer can coexist with scleroderma, the temporal relationship between the two seems random, with cancer antedating scleroderma in some cases, or following it in others. The interval between the cancer diagnosis and scleroderma can range from years to decades. There is one exception, however. In scleroderma patients with cancer whose antibodies are directed against RNA polymerase III, scleroderma almost always arises within 4 years of the detection of cancer. This is in striking contrast to the majority of patients with scleroderma and cancer, who have autoantibodies to centromere (CENPB) or topoisomerase-1. What is it about anti-RNA polymerase III autoimmunity that links scleroderma with cancer?

To address this conundrum, Rosen et al. revisited an old hypothesis – that the  antigen triggering autoimmune diseases in some patients is actually the tumor itself! Rosen et al analyzed genetic alterations in tumor tissue from eight patients with scleroderma and cancer who were RNA polymerase III-positive, and eight patients with scleroderma and cancer who were RNA polymerase III-negative. These latter had autoantibodies to CENPB or to Topo-1. Tumors from RNA polymerase III-positive patients were found to have clear-cut genetic alterations (missense mutation or loss of heterozygosity) involving the POLR3A gene encoding RNA polymerase III PRC1 subunit. In contrast, none of the scleroderma patients with cancer who had other autoantibodies had genetic alterations in ROLR3A.

Moreover, the authors go on to demonstrate a unique T cell subset, found only in RNA polymerase III-positive patients with scleroderma, that reacts specifically with the RNA Polymerase III epitope. This cell-mediated self-reactivity might represent an anti-cancer immune response targeting the tumors with the somatic alterations in POLR3A.  These results lead to the speculation that a nascent tumor harboring a genetic alteration might generate an antibody response that, on the one hand, leads to immune attack against the tumor itself (a phenomenon called tumor immune editing), but on the other, leads to an autoimmune disease like scleroderma.

In this scenario, some cases of scleroderma might be viewed as a paraneoplastic condition, and anti-RNA Polymerase III autoimmunity might actually represent an ineffective anti-cancer response whose goal is to eradicate the tumor harboring the genetic alteration. Perhaps RNA polymerase III-positive scleroderma patients who have no detectable cancer have succeeded in deploying the break in immune tolerance to rid themselves of the tumor.

A major unanswered question remains: how does an  antigen-specific immune response specifically directed against RNA polymerase III result in the microvascular injury and tissue fibrosis that are the hallmarks of scleroderma?


Image credit:  Anne Weston, LRI, CRUK. This image is made available from and used under the Creative Commons license CC-BY-NC-ND 2.0