Insight into Schmid metaphyseal chondrodysplasia from the crystal structure of the collagen X NC1 domain trimer

Collagen X is expressed specifically in the growth plate of long bones. Its C1q-like C-terminal NC1 domain forms a stable homotrimer and is crucial for collagen X assembly. Mutations in the NC1 domain cause Schmid metaphyseal chondrodysplasia (SMCD). The crystal structure at 2.0 A resolution of the human collagen X NC1 domain reveals an intimate trimeric assembly strengthened by a buried cluster of calcium ions. Three strips of exposed aromatic residues on the surface of NC1 trimer are likely to be involved in the supramolecular assembly of collagen X. Most internal SMCD mutations probably prevent protein folding, whereas mutations of surface residues may affect the collagen X suprastructure in a dominant-negative manner.     

Facilitation, competition, and vegetation patchiness: from scale free distribution to patterns

A new technique for the modeling of perennial vegetation patchiness in the arid/semiarid climatic zone is suggested. Incorporating the stochasticity that affects life history of seedlings and the deterministic dynamics of soil moisture and biomass, this model is flexible enough to yield qualitatively different forms of spatial organization. In the facilitation-dominated regime, scale free distribution of patch sizes is observed, in correspondence with recent field studies. In the competition controlled case, on the other hand, power-law statistics is valid up to a cutoff, and an intrinsic length scale appears.     

Catalyst-induced growth with limited catalyst lifespan and competition

Spatially extended catalyst-induced growth processes are studied. This type of processes exists in all domains of biology, ranging from ecology (nutrients and growth), through immunology (antigens and lymphocytes) to molecular biology (signaling molecules initiating signaling cascades). The extinction-proliferation transition is considered for a system containing discrete catalysts (A) that induces the proliferation of a discrete reactant (B). The realization of this model on an infinite capacity d-dimensional discrete lattice for immortal catalysts has been previously considered (the AB model). It was shown that the adaptation of the reactants to the diffusive noise induced by stochastic fluctuations of catalyst density yields proliferation even if the average environmental conditions lead to extinction. This model is extended here to include more realistic situations, like finite lifespan of the catalysts and finite carrying capacity of the reactants. By using a combination of Monte Carlo simulation, percolation-theory-based estimations and an analytic perturbative analysis, the asymptotic behavior of these systems is studied. In both cases studied, it turns out that the overall survival of the reactant population at the long run is based on the size and shape of a typical single colony, related to the localized proliferation around spatio-temporal catalyst density fluctuations. If the density of these colonies (based on the lifetime of the spatial fluctuation and the carrying capacity of the medium) is large enough, i.e. above the percolation threshold, the reactant population survives even in (on average) hostile environment. This model provides a new insight on the population dynamics in chemical, biological and ecological systems.     

Stabilization of metapopulation cycles: toward a classification scheme

The stability of population oscillations in ecological systems is considered. Experiments suggest that in many cases the single patch dynamics of predator-prey or host-parasite systems is extinction prone, and stability is achieved only when the spatial structure of the population is expressed via desynchronization between patches. A few mechanisms have been suggested so far to explain the inability of dispersal to synchronize the system. Here we compare a recently discovered mechanism, based on the dependence of the angular velocity on the oscillation amplitude, with other, already known conditions for desynchronization. Using a toy model composed of diffusively coupled oscillators we suggest a classification scheme for stability mechanisms, a scheme that allows for either a priori (based on the system parameters) or a posteriori (based on local measurements) identification of the dominant process that yields desynchronization.     

Abundance Patterns of Landbirds in Restored and Remnant Riparian Forests on the Sacramento River, California, U.S.A.

Riparian vegetation along the Sacramento River—California's largest river—has been almost entirely lost, and several wildlife species have been extirpated or have declined as a result. Large-scale restoration efforts are focusing on revegetating the land with native plants. To evaluate restoration success, we conducted surveys of landbirds on revegetated and remnant riparian plots from 1993 to 2003. Our objectives were to estimate population trends of landbirds, compare abundance patterns over time between revegetated and remnant riparian forests, and evaluate abundance in relation to restoration age. Of the 20 species examined, 11 were increasing, 1 was decreasing (Lazuli Bunting [ Passerina amoena ]), and 8 showed no trend. The negative trend for Lazuli Bunting is consistent with information on poor reproductive success and with Breeding Bird Survey results. There was no apparent guild association common to species with increasing trends. Nine species were increasing on revegetated and remnant plots, four were increasing on revegetated plots only, three were increasing on remnant plots only, the Lazuli Bunting was decreasing on both, and three species were stable on both. Although many species were increasing at a faster rate on revegetated plots, their abundance did not reach that of the remnant plots. For revegetated plots, "year since planting" was a strong predictor of abundance trends for 13 species: positive for 12, negative for 1. Our study shows that restoration activities along the Sacramento River are successfully providing habitat for a diverse community of landbirds and that results from bird monitoring provide a meaningful way to evaluate restoration success.     

Neuron-specific ablation of the Krabbe disease gene galactosylceramidase in mice results in neurodegeneration

Krabbe disease is caused by a deficiency of the lysosomal galactosylceramidase (GALC) enzyme, which results in the accumulation of galactosylceramide (GalCer) and psychosine. In Krabbe disease, the brunt of demyelination and neurodegeneration is believed to result from the dysfunction of myelinating glia. Recent studies have shown that neuronal axons are both structurally and functionally compromised in Krabbe disease, even before demyelination, suggesting a possible neuron-autonomous role of GALC. Using a novel neuron-specific Galc knockout (CKO) model, we show that neuronal Galc deletion is sufficient to cause growth and motor coordination defects and inflammatory gliosis in mice. Furthermore, psychosine accumulates significantly in the nervous system of neuron-specific Galc-CKO. Confocal and electron microscopic analyses show profound neuro-axonal degeneration with a mild effect on myelin structure. Thus, we prove for the first time that neuronal GALC is essential to maintain and protect neuronal function independently of myelin and may directly contribute to the pathogenesis of Krabbe disease.

Krabbe disease is a demyelinating neurodegenerative disorder caused by a deficiency of the enzyme lysosomal galactosylceramidase (GALC), which results in the accumulation of galactosylceramide and psychosine. This study uses a novel neuron-specific knockout model in the first in vivo attempt to investigate the role of neuronal GALC in neuronal function and the etiology of Krabbe disease.     

The Price of a Neglected Zoonosis: Case-Control Study to Estimate Healthcare Utilization Costs of Human Brucellosis

Human brucellosis has reemerged as a serious public health threat to the Bedouin population of southern Israel in recent years. Little is known about its economic implications derived from elevated healthcare utilization (HCU). Our objective was to estimate the HCU costs associated with human brucellosis from the insurer perspective. A case-control retrospective study was conducted among Clalit Health Services (CHS) enrollees. Brucellosis cases were defined as individuals that were diagnosed with brucellosis at the Clinical Microbiology Laboratory of Soroka University Medical Center in the 2010–2012 period (n = 470). Control subjects were randomly selected and matched 1:3 by age, sex, clinic, and primary physician (n = 1,410). HCU data, demographic characteristics and comorbidities were obtained from CHS computerized database. Mean±SD age of the brucellosis cases was 26.6±17.6 years. 63% were male and 85% were Bedouins. No significant difference in Charlson comorbidity index was found between brucellosis cases and controls (0.41 vs. 0.45, respectively, P = 0.391). Before diagnosis (baseline), the average total annual HCU cost of brucellosis cases was slightly yet significantly higher than that of the control group ($439 vs. $382, P<0.05), however, no significant differences were found at baseline in the predominant components of HCU, i.e. hospitalizations, diagnostic procedures, and medications. At the year following diagnosis, the average total annual HCU costs of brucellosis cases was significantly higher than that of controls ($1,327 vs. $380, respectively, P<0.001). Most of the difference stems from 7.9 times higher hospitalization costs (p<0.001). Additional elevated costs were 3.6 times higher laboratory tests (P<0.001), 2.8 times higher emergency room visits (P<0.001), 1.8 times higher medication (P<0.001) and 1.3 times higher diagnostic procedures (P<0.001). We conclude that human brucellosis is associated with elevated HCU costs. Considering these results in cost-effective analyses may be crucial for both reducing health inequities and optimal allocation of health systems’ scarce resources.     

EFA6 regulates endosomal trafficking and affects early endosomes in polarized MDCK cells

The small-GTPase family of ADP ribosylation factors (ARFs) recruit coat proteins to promote vesicle budding. ARFs are activated by an association with sec7-containing exchange factors which load them with GTP. In epithelial cells, the small GTPase ARF6 operates within the endocytic system and has been shown to associate with ARNO to promote apical endocytosis and early to late endosomal trafficking. EFA6 has been shown to stimulate tight-junction formation and maintenance. Here, we show that in polarized epithelial MDCK cells, EFA6 is localized to early endosomes, causes their dramatic enlargement, and promotes basolateral targeting of IgA, which is normally targeted to the apical PM. These results suggest that the physiological function of ARF6 within the endocytic system is regulated by the exchange factor it associates with.