Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.     

Energetic constraints on the diet of terrestrial carnivores

Species in the mammalian order Carnivora exhibit a huge diversity of life histories with body sizes spanning more than three orders of magnitude. Despite this diversity, most terrestrial carnivores can be classified as either feeding on invertebrates and small vertebrates or on large vertebrates. Small carnivores feed predominantly on invertebrates probably because they are a superabundant resource (sometimes 90% of animal biomass); however, intake rates of invertebrate feeders are low, about one tenth of those of vertebrate feeders. Although small carnivores can subsist on this diet because of low absolute energy requirements, invertebrate feeding appears to be unsustainable for larger carnivores. Here we show, by reviewing the most common live prey in carnivore diets, that there is a striking transition from feeding on small prey (less than half of predator mass) to large prey (near predator mass), occurring at predator masses of 21.5-25 kg. We test the hypothesis that this dichotomy is the consequence of mass-related energetic requirements and we determine the predicted maximum mass that an invertebrate diet can sustain. Using a simple energetic model and known invertebrate intake rates, we predict a maximum sustainable mass of 21.5 kg, which matches the point where predators shift from small to large prey.     

Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP.

Proteolytic processing of amyloid precursor protein (APP) generates amyloid-beta peptide and has been implicated in the pathogenesis of Alzheimer's disease. However, the normal function of APP, whether this function is related to the proteolytic processing of APP, and where this processing takes place in neurons in vivo remain unknown. We have previously shown that the axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin-I, a microtubule motor protein. Here we identify an axonal membrane compartment that contains APP, beta-secretase and presenilin-1. The fast anterograde axonal transport of this compartment is mediated by APP and kinesin-I. Proteolytic processing of APP can occur in the compartment in vitro and in vivo in axons. This proteolysis generates amyloid-beta and a carboxy-terminal fragment of APP, and liberates kinesin-I from the membrane. These results suggest that APP functions as a kinesin-I membrane receptor, mediating the axonal transport of beta-secretase and presenilin-1, and that processing of APP to amyloid-beta by secretases can occur in an axonal membrane compartment transported by kinesin-I.     

A two-solar-mass neutron star measured using Shapiro delay

Neutron stars are composed of the densest form of matter known to exist in our Universe, the composition and properties of which are still theoretically uncertain. Measurements of the masses or radii of these objects can strongly constrain the neutron star matter equation of state and rule out theoretical models of their composition. The observed range of neutron star masses, however, has hitherto been too narrow to rule out many predictions of 'exotic' non-nucleonic components. The Shapiro delay is a general-relativistic increase in light travel time through the curved space-time near a massive body. For highly inclined (nearly edge-on) binary millisecond radio pulsar systems, this effect allows us to infer the masses of both the neutron star and its binary companion to high precision. Here we present radio timing observations of the binary millisecond pulsar J1614-2230 that show a strong Shapiro delay signature. We calculate the pulsar mass to be (1.97?±?0.04)M(⊙), which rules out almost all currently proposed hyperon or boson condensate equations of state (M(⊙), solar mass). Quark matter can support a star this massive only if the quarks are strongly interacting and are therefore not 'free' quarks.     

Sporting contests: seeing red? Putting sportswear in context

The shirt colour worn by sportsmen can affect the behaviour of the competitors, but Hill and Barton show that it may also influence the outcome of contests. By analysing the results of men's combat sports from the Athens 2004 Olympics, they found that more matches were won by fighters wearing red outfits than by those wearing blue; they suggest that red might confer success because it is a sign of dominance in many animal species and could signal aggression in human contests. Here we use another data set from the 2004 Olympics to show that similar winning biases occur in contests in which neither contestant wears red, indicating that a different mechanism may be responsible for these effects.     

New ages for human occupation and climatic change at Lake Mungo,Australia

Australia's oldest human remains, found at Lake Mungo, include the world's oldest ritual ochre burial (Mungo III) and the first recorded cremation (Mungo I). Until now, the importance of these finds has been constrained by limited chronologies and palaeoenvironmental information. Mungo III, the source of the world's oldest human mitochondrial DNA, has been variously estimated at 30 thousand years (kyr) old, 42-45 kyr old and 62 +/- 6 kyr old, while radiocarbon estimates placed the Mungo I cremation near 20-26 kyr ago. Here we report a new series of 25 optical ages showing that both burials occurred at 40 +/- 2 kyr ago and that humans were present at Lake Mungo by 50-46 kyr ago, synchronously with, or soon after, initial occupation of northern and western Australia. Stratigraphic evidence indicates fluctuations between lake-full and drier conditions from 50 to 40 kyr ago, simultaneously with increased dust deposition, human arrival and continent-wide extinction of the megafauna. This was followed by sustained aridity between 40 and 30 kyr ago. This new chronology corrects previous estimates for human burials at this important site and provides a new picture of Homo sapiens adapting to deteriorating climate in the world's driest inhabited continent.     

Flightless birds: when did the dodo become extinct?

The extinction of the dodo (Raphus cucullatus L.; Fig. 1) is commonly dated to the last confirmed sighting in 1662, reported by Volkert Evertsz on an islet off Mauritius. By this time, the dodo had become extremely rare - the previous sighting having been 24 years earlier - but the species probably persisted unseen beyond this date. Here we use a statistical method to establish the actual extinction time of the dodo as 1690, almost 30 years after its most recent sighting.