Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases

The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15, in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis in gastrointestinal disease.     

Some aspects of succession in the spruce-fir forest zone of northern Utah

A site in the Rocky Mountain subalpine forest zone with which a series of hypotheses concerning ecosystem succession was tested is characterized. Succession from herb-dominated meadows to climax forests of Engelmann spruce and subalpine fir can follow at least four identified pathways. After fire, spruce and fir may reinvade a site directly, follow invasion by aspen, or follow invasion by lodgepole pine, the pathway depending on a combination of physical and biotic factors. In other cases, succession begins with long-established meadows which do not owe their existence to fire. In this latter pathway, aspen invades meadows by suckering and changes the environment near the soil surface so as to facilitate establishment of the climax tree species. The biota and soils of four characteristic seral stages (meadow, aspen, fir, spruce-fir) in this latter pathway are described.     

Breeding behavior of the Plumbeous Vireo in New Mexico

The Plumbeous Vireo ( Vireo plumbeus ) is a poorly studied songbird species that breeds within the interior western United States and Mexico. We studied the breeding behavior of Plumbeous Vireos within pinyon-juniper habitats in northeastern New Mexico in 1996 and 1997. Over both years we located and monitored 40 nests and conducted behavioral observations throughout the nesting cycle. From these observations we described and compared basic behavioral traits of male and female vireos during their nest-building, egg-laying, incubation, and nestling stages, and their response to potential predators near the nest. Male vireos displayed potential nest sites to females, but the females selected the site to be used and built most of the nest. Vireos often did not initiate egg-laying until 2-3 d after nest completion. The female tended to incubate eggs and brood nestlings more than the male, but both parents contributed equally in provisioning the young. Brown-headed Cowbirds ( Molothrus ater ) parasitized 77% of nests in 1996, 63% in 1997, and parasitism was the primary cause of nest failure in this population. The conspicuousness of vireos around the nest, particularly during the nest-building stage, may contribute to high parasitism levels. Vireo aggression near the nest may also act as a cue to help cowbirds locate nests.     

Condition models for wintering Northern Pintails in the Southern High Plains

Three condition models for wintering Northern Pintails ( Anas acuta ) were tested for their ability to predict fat mass, logarithm of fat mass, or a condition index (CI) incorporating fat mass. Equations generated to predict fat mass and the logarithm of fat mass accounted for more than 69% of the variation in these dependent variables. Log transformations of body mass, wing length, and total length explained at least 60% of the variation in CI. All models performed better on an independent data set. Mean prediction error was minimal (≤8% of measured variables) and negative for all models. Regression models apply to live and dead pintails and thus represent tools that have utility in a wide variety of studies on pintail condition.