Michael K. Hoffmann

The Novel Lipopolysaccharide-Binding Protein CRISPLD2 Is a Critical Serum Protein to Regulate Endotoxin Function

LPS is an immunostimulatory component of Gram-negative bacteria. Acting on the immune system in a systemic fashion, LPS exposes the body to the hazard of septic shock. In this study we report that cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2/Crispld2; human and mouse/rat versions, respectively), expressed by multitissues and leukocytes, is a novel LPS-binding protein. As a serum protein, median CRISPLD2 concentrations in health volunteers and umbilical cord blood samples are 607 μg/ml and 290 μg/ml, respectively. Human peripheral blood granulocytes and mononuclear cells including monocytes, NK cells, and T cells spontaneously release CRISPLD2 (range, 0.2–0.9 μg/ml) and enhance CRISPLD2 secretion (range, 1.5–4.2 μg/ml) in response to stimulation of both LPS and humanized anti-human TLR4-IgA Ab in vitro. CRISPLD2 exhibits significant LPS binding affinity similar to that of soluble CD14, prevents LPS binding to target cells, reduces LPS-induced TNF-α and IL-6 production, and protects mice against endotoxin shock. In in vivo experiments, serum Crispld2 concentrations increased in response to a nontoxic dose of LPS and correlated negatively with LPS lethality, suggesting that CRISPLD2 serum concentrations not only are indicators of the degree of a body’s exposure to LPS but also reflect an individual’s LPS sensitivity.

Extinction risk is most acute for the world’s largest and smallest vertebrates

Significance Determining the drivers of extinction risk has been a key pursuit of conservation biology. Considering that body mass could be a strong predictor of extinction risk, we constructed a global database of body masses for 27,647 vertebrate species. Results show that the smallest- and largest-bodied vertebrates have elevated extinction risk. The largest vertebrates are mostly threatened by direct killing by humans, whereas the smallest species are more likely to have restricted geographic ranges—an important predictor of extinction risk—and be threatened by habitat degradation. Declines of large and small vertebrate species will truncate the size distributions characterizing these taxa, jeopardizing ecosystem services to humans, and generating cascading ecological and evolutionary effects on other species and processes. Extinction risk in vertebrates has been linked to large body size, but this putative relationship has only been explored for select taxa, with variable results. Using a newly assembled and taxonomically expansive database, we analyzed the relationships between extinction risk and body mass (27,647 species) and between extinction risk and range size (21,294 species) for vertebrates across six main classes. We found that the probability of being threatened was positively and significantly related to body mass for birds, cartilaginous fishes, and mammals. Bimodal relationships were evident for amphibians, reptiles, and bony fishes. Most importantly, a bimodal relationship was found across all vertebrates such that extinction risk changes around a body mass breakpoint of 0.035 kg, indicating that the lightest and heaviest vertebrates have elevated extinction risk. We also found range size to be an important predictor of the probability of being threatened, with strong negative relationships across nearly all taxa. A review of the drivers of extinction risk revealed that the heaviest vertebrates are most threatened by direct killing by humans. By contrast, the lightest vertebrates are most threatened by habitat loss and modification stemming especially from pollution, agricultural cropping, and logging. Our results offer insight into halting the ongoing wave of vertebrate extinctions by revealing the vulnerability of large and small taxa, and identifying size-specific threats. Moreover, they indicate that, without intervention, anthropogenic activities will soon precipitate a double truncation of the size distribution of the world’s vertebrates, fundamentally reordering the structure of life on our planet.

IUCN's encounter with 007: safeguarding consensus for conservation

A controversy at the 2016 IUCN World Conservation Congress on the topic of closing domestic ivory markets (the 007, or so-called James Bond, motion) has given rise to a debate on IUCNs value proposition. A cross-section of authors who are engaged in IUCN but not employed by the organization, and with diverse perspectives and opinions, here argue for the importance of safeguarding and strengthening the unique technical and convening roles of IUCN, providing examples of what has and has not worked. Recommendations for protecting and enhancing IUCNs contribution to global conservation debates and policy formulation are given.

Reply to Kalinkat et al.: Smallest terrestrial vertebrates are highly imperiled

Kalinkat et al. (1) discuss the biodiversity crisis in their reply to our article “Extinction risk is most acute for the world’s largest and smallest vertebrates” (2). We agree with Kalinkat et al. (1) that small freshwater species tend to have elevated extinction risk, an issue that we highlight in our paper (2). Specifically, 41% (36 of 87) of freshwater vertebrate species with body masses ≤ 0.001 kg are listed as threatened compared with 29% (1,578 of 5,428) threatened for … nn[↵][1]1To whom correspondence should be addressed. Email: bill.ripple{at}oregonstate.edu.nn [1]: #xref-corresp-1-1