BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character

This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.     

Natural and land-use history of the Northwest mountain ecoregions (USA) in relation to patterns of plant invasions

Although the Northwest currently has the least proportion of non-native invasive plant species relative to other regions of North America, invasions continue to increase into the mountainous areas of the region. Landscape structure, such as the variation found along the complex gradients of the Northwest mountain ecoregions, affects the expansion of invasive plant species and the invasibility of plant communities. Also, the history of land use and current use patterns affect the expansion of invasive plants, and many of the deteriorated environments in the region's mountains may invite and stabilize plant invasions. We examined the patterns of invasive plant diversity in Northwest mountain ecoregions, as derived from literature sources, to analyze which factors influence plant invasions. Our analysis found altered riparian systems and disturbed forests to be especially vulnerable to plant invasion. Conversely, alpine and wilderness areas are still relatively unaffected by invasive plants. Both riparian and alpine communities, while making up a relatively small area across Northwest mountain ecoregions, have significant ecological importance and deserve special protection from invasive plant introductions. Human settlement at low elevations and intense land use of upland forests will likely continue to enhance invasive plant introductions into Northwest mountain ecosystems. Knowledge of the relationships between biological and environmental factors, disturbance, and human land use will be critical for future management strategies that proactively locate, prevent, or contain plant invasions in the mountains of the Northwest.     

Dual function of protein confinement in chaperonin-assisted protein folding.

The GroEL/GroES chaperonin system mediates the folding of a range of newly synthesized polypeptides in the bacterial cytosol. Using a rapid biotin-streptavidin-based inhibition of chaperonin function, we show that the cage formed by GroEL and its cofactor GroES can have a dual role in promoting folding. First, enclosure of nonnative protein in the GroEL:GroES complex is essential for folding to proceed unimpaired by aggregation. Second, folding inside the cage can be significantly faster than folding in free solution, independently of ATP-driven cycles of GroES binding and release. This suggests that confinement of unfolded protein in the narrow hydrophilic space of the chaperonin cage smoothes the energy landscape for the folding of some proteins, increasing the flux of folding intermediates toward the native state.     

Homologies between higher plant and algal 25S cytoplasmic ribosomal RNA

Using heat and urea treatment, the degradation products of denatured 25S cytoplasmic ribosomal RNA from jack bean (a higher plant) and $\text{Chlamydomonas reinhardi}$ (an alga) were compared. Several specific modes of 25S RNA breakdown are postulated. The results suggest that (1) both higher plant algal 25S RNA may contain homologous endonuclease susceptible regions as judged by the stoichiometry of degradation and (2) that similar secondary structural properties of 25S cytoplasmic RNA have been conserved by evolution in the plant kingdom.     

Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme

Recessive mutations, revealed by loss of the wild-type allele, have been associated with the development of a variety of cancers in children and adults. Polymorphic chromosome 10 markers were used to screen paired tumor and lymphocyte DNA samples in 13 patients with glioblastoma multiforme. Ten patients showed loss of constitutional heterozygosity in the tumor samples. This finding suggests that a recessive gene involved in the development of glioblastoma multiforme is present on chromosome 10.