Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage

Many mutations leading to human disease are the result of single DNA base pair changes that cannot be identified by Southern analysis. This has prompted the development of alternative assays for point mutation detection. The recently described ribonuclease A cleavage procedure, with a polyuridylic acid-paper affinity chromatography step, has been used to identify the mutational lesions in the hypoxanthine phosphoribosyltransferase (HPRT) messenger RNAs of patients with Lesch-Nyhan syndrome. Distinctive ribonuclease A cleavage patterns were identified in messenger RNA from 5 of 14 Lesch-Nyhan patients who were chosen because no HPRT Southern or Northern blotting pattern changes had been found. This approach now allows HPRT mutation detection in 50 percent of the cases of Lesch-Nyhan syndrome. The polyuridylic acid-paper affinity procedure provides a general method for analysis of low abundance messenger RNAs.     

Spatial Response of Mammals to Late Quaternary Environmental Fluctuations

Analyses of fossil mammal faunas from 2945 localities in the United States demonstrate that the geographic ranges of individual species shifted at different times, in different directions, and at different rates in response to late Quaternary environmental fluctuations. The geographic pattern of faunal provinces was similar for the late Pleistocene and late Holocene, but differing environmental gradients resulted in dissimilar species composition for these biogeographic regions. Modern community patterns emerged only in the last few thousand years, and many late Pleistocene communities do not have modern analogs. Faunal heterogeneity was greater in the late Pleistocene.     

Extracellular replication of Listeria monocytogenes in the murine gall bladder

The bacterium Listeria monocytogenes can cause a life-threatening systemic illness in humans. Despite decades of progress in animal models of listeriosis, much remains unknown about the processes of infection and colonization. Here, we report that L. monocytogenes can replicate in the murine gall bladder and provide evidence that its replication there is extracellular and intraluminal. In vivo bioluminescence imaging was employed to determine the location of the infection over time in live animals, revealing strong signals from the gall bladder over a period of several days, in diseased as well as asymptomatic animals. The data suggest that L. monocytogenes may be carried in the human gall bladder.     

Seed dispersal by weta

Weta are giant, flightless grasshoppers that are endemic to New Zealand. In the absence of native mammals, weta are thought to perform similar ecological functions. As such, they might be expected to be important seeds dispersers. However, insects are not known to consume fleshy fruits and to disperse seeds after gut passage. We conducted a series of observations and experiments to test whether weta form mutualistic partnerships with fleshy-fruited plants as seed dispersers, similar to small mammals elsewhere in the world. Results showed that weta are indeed effective seeds dispersers, providing an example of ecological convergence between unrelated organisms.     

A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a strong genetic predisposition. A locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) have not been identified. We genotyped 581 AMD cases and 309 normal controls in a Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients revealed that the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein. We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis.     

High and dry in days gone by: Life-history theory predicts Appalachian mountain stream fish assemblage transformation during historical drought

Understanding the ecological dimensions of drought is critical for predicting how humans and nature will be affected by the expected increased prevalence of drought in the future. We tested life-history-based predictions for fish assemblage responses to drought using retrospective analysis of long-term (1986–2003) fish surveys from two streams in the Appalachian Mountains of North America. We hypothesised that (1) fish assemblage composition would correlate with wet and dry hydrologic conditions as assemblages fluctuated within a loose equilibrium and (2) life-history traits of fishes would correlate with dry versus wet periods such that opportunistic life-history strategists would dominate during drought. Results showed fish assemblage changes in Little River and Cataloochee Creek correlated with drought severity measured one year prior to fish surveys. Fish assemblages at all three sampling sites in Little River and two sites in Cataloochee Creek fluctuated within a loose equilibrium, while the remaining two sites in Cataloochee Creek indicated directional change. Life-history traits for fishes in Cataloochee Creek correlated with one-year time lag fluctuations in drought caused by opportunistic species being dominant during drought and periodic/equilibrium species dominant during wet periods. Time series plots of fish abundances aggregated by life-history strategy revealed dominance of opportunistic species emerged at the onset of a multi-year drought spanning 1998–2004, particularly for the two sites undergoing directional change. Our work provides empirical evidence for theoretical linkages between life history and environmental fluctuations and can ultimately be used to predict stream fish community response to future drought regimes.