Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism

The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we asked whether LMO4 is required for metabolic homeostasis. LMO4 mutant mice exhibited early onset adiposity. These mice had reduced energy expenditure and impaired thermogenesis together with reduced sympathetic outflow to adipose tissues. The peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling at the hypothalamus to control food intake, energy expenditure, and fat metabolism. Intracerebroventricular infusion of leptin suppressed feeding similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was impaired and activation of Stat3 in the VMH was blunted in these mice. Thus, our study identifies LMO4 as a novel modulator of leptin function in selective hypothalamic nuclei to regulate fat metabolism.     

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.     

Stem growth and longevity dynamics for Salix arizonica dorn

Diameter-age relationships of Salix arizonica (Arizona willow) stems were investigated for 5 populations on the Markagunt, Paunsaugunt, and Sevier plateaus in southern and central Utah. Of the 430 stems studied, none exceeded 26 mm in diameter at ground level (estimated age of 19 yr). Equations developed for predicting age from stem diameters consistently accounted for over 90% of the observed variation. Slopes of predictive equations were homogenous across the 3 sites considered in detail. At 2 sties 46% and 38% of the stems exceed 10 mm (～ 7 yr old) diameter at ground level. At a 3rd site, no stems survived to exceed that size. Stem-age profiles at specific sites may thus be useful for assessing the relative favorability of local environments for the species.     

Alkaloidal relationships in the genus Arctomecon (Papaveraceae) and herbivory in A. humilis

The previously reported alkaloids (including protopines, benzophenanthridines, tetrahydrobenzylisoquinolines, and protoberberines) of the genus Arctomecon (Papaveraceae) are discussed in relation to their distribution in the plant kingdom, in the Papaveraceae, and among the three species of Arctomecon . The biological activity of these alkaloids is discussed, and possible implications for herbivore and plant-insect interactions in A. humilis are presented.     

Selecting wilderness areas to conserve Utah's biological diversity

Congress is currently evaluating the wilderness status of Bureau of Land Management (BLM) public lands in Utah. Wilderness areas play many important roles, and one critical role is the conservation of biological diversity. We propose that objectives for conserving biodiversity on BLM lands in Utah be to (1) ensure the long-term population viability of native animal and plant species, (2) maintain the critical ecological and evolutionary processes upon which these species depend, and (3) preserve the full range of communities, successional stages, and environmental gradients. To achieve these objectives, wilderness areas should be selected so as to protect large, contiguous areas, augment existing protected areas, buffer wilderness areas with multiple-use public lands, interconnect existing protected areas with dispersal and movement corridors, conserve entire watersheds and elevational gradients, protect native communities from invasions of exotic species, protect sites of maximum species diversity, protect sites with rare endemic species, and protect habitats of threatened and endangered species. We use a few comparatively well-studied taxa as examples to highlight the importance of particular BLM lands.     

Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci

We have carried out a genome screen for atopic dermatitis (AD) and have identified linkage to AD on chromosomes 1q21, 17q25 and 20p. These regions correspond closely with known psoriasis loci, as does a previously identified AD locus on chromosome 3q21. The results indicate that AD is influenced by genes with general effects on dermal inflammation and immunity.     

Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome

We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.