Identification of an HD patient with a (CAG)180 repeat expansion and the propagation of highly expanded CAG repeats in lambda phage

The Huntington’s disease mutation has been identified as a CAG/polyglutamine repeat expansion in a large gene of unknown function. In order to develop the transgenic systems necessary to uncover the molecular pathology of this disorder, it is necessary to be able to manipulate highly expanded CAG repeats in a cloned form. We have identified a patient with an expanded allele of greater than 170 repeat units and have cloned the mutant allele in the lambda zap vector. The recovery of highly expanded repeats after clone propagation was more efficient when repeats were maintained as lambda phage clones rather than as the plasmid counterparts. Manipulation of the repeats as phage clones has enabled us to generate Huntington’s disease transgenic mice that contain highly expanded (CAG)₁₁₅–(CAG)₁₅₀ repeats and that develop a progressive neurological phenotype. Received: 7 October 1996 / Revised: 5 December 1996     

Partitioning of respiratory mechanics in mechanically ventilated patients.

In ten mechanically ventilated patients, six with chronic obstructive pulmonary disease (COPD) and four with pulmonary edema, we have partitioned the total respiratory system mechanics into the lung (l) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant-flow inflation (J. Appl. Physiol. 58: 1840-1848, 1985). Intrinsic positive end-expiratory pressure (PEEPi) was present in eight patients (range 1.1-9.8 cmH2O) and was due mainly to PEEPi,L (80%), with a minor contribution from PEEPi,w (20%), on the average. The increase in respiratory elastance and resistance was determined mainly by abnormalities in lung elastance and resistance. Chest wall elastance was slightly abnormal (7.3 +/- 2.2 cmH2O/l), and chest wall resistance contributed only 10%, on the average, to the total. The work performed by the ventilator to inflate the lung (WL) averaged 2.04 +/- 0.59 and 1.25 +/- 0.21 J/l in COPD and pulmonary edema patients, respectively, whereas Ww was approximately 0.4 J/l in both groups, i.e., close to normal values. We conclude that, in mechanically ventilated patients, abnormalities in total respiratory system mechanics essentially reflect alterations in lung mechanics. However, abnormalities in chest wall mechanics can be relevant in some COPD patients with a high degree of pulmonary hyperinflation.     

Legacy microsite effect on the survival of bitterbrush outplantings after prescribed fire: capitalizing on spatial variability to improve restoration

Restoration of shrubs in arid and semi‐arid rangelands is hampered by low success rates. Planting shrub seedlings is a method used to improve success in these rangelands; however, it is expensive and labor intensive. The efficiency of shrub restoration could be improved by identifying microsites where shrub survival is greater. Bitterbrush (Purshia tridentata Pursh DC) is an important shrub to wildlife that has declined because of conifer encroachment, excessive defoliation, wildfires, and low recruitment. We investigated planting bitterbrush seedlings in western juniper (Juniperus occidentalis ssp. occidentalis Hook) encroached shrublands after prescribed fire was used to control trees. Bitterbrush seedlings were planted in under (canopy) and between (interspace) former juniper canopies at five blocks and evaluated for three growing seasons. Bitterbrush survival was greater than 50% in the former canopy, but only 5% in the interspace microsite by the third growing season. Growth of bitterbrush was also greater in the former canopy compared with the interspace, potentially due to markedly less perennial vegetation in this microsite. Exotic annual grasses and annual forbs became prevalent in the former canopy in the second and third growing season, suggesting that soil resource availability was greater in this microsite. These results suggest that restoration success will vary by specific locations within a burned landscape and that this variability can be used to improve restoration efficiency. In this situation, bitterbrush restoration can be improved by planting seedlings in former canopy compared with interspace microsites.     

Probability-based model of protein-protein interactions on biological timescales

Background  

Simulation methods can assist in describing and understanding complex networks of interacting proteins, providing fresh insights into the function and regulation of biological systems. Recent studies have investigated such processes by explicitly modelling the diffusion and interactions of individual molecules. In these approaches, two entities are considered to have interacted if they come within a set cutoff distance of each other.     

Spatial variation in parasite-induced mortality in an amphipod: shore height versus exposure history

Characterizing the causes of spatial and temporal variation in parasite-induced mortality under natural conditions is crucial to better understanding the factors driving host population dynamics. Our goal was to quantify this variation in the amphipod Paracalliope novizealandiae, a second intermediate host of the trematode, Maritrema novaezealandensis. If infection and development of trematode metacercariae are benign, we expected mature metacercariae to accumulate within amphipods inhabiting high infestation areas. In field samples, intensity levels of mature metacercariae decreased linearly when amphipods harbored >5 immature metacercariae. This finding is consistent with the hypothesis that the parasite can be detrimental at high intensities of infection. Short-term field experiments showed that host survival also declines with the intensity of new infections and drops below 80% when early stage metacercariae reach 10 amphipod^?1. However, parasite effects varied over space and time. High-shore amphipods suffered an increased risk of infection in the summer and a lower likelihood of survival: there was a 10–30% decrease in survivorship for any given infection intensity at high- versus low-shore locations. We also tested for differences in the susceptibility of naive and exposed populations using transplant experiments, and found that naive amphipods acquired greater parasite loads (on average, 4.7 vs. 2.8 metacercariae amphipod^?1). Because survival decreases rapidly with infection intensity of both early- and late-stage metacercariae, naive populations would suffer considerably if the parasite were to increase its range. Our results indicate that trematode infections cause high mortality in amphipods during summer months under natural conditions, and emphasize that the effects of parasitism vary at local spatial scales and with exposure history.