The A326S mutant of Gialpha1 as an approximation of the receptor-bound state

Agonist-bound heptahelical receptors activate heterotrimeric G proteins by catalyzing exchange of GDP for GTP on their alpha subunits. In search of an approximation of the receptor-alpha subunit complex, we have considered the properties of A326S Gialpha1, a mutation discovered originally in Gsalpha (Iiri, T., Herzmark, P., Nakamoto, J. M., Van Dop, C., and Bourne, H. R. (1994) Nature 371, 164-168) that mimics the effect of receptor on nucleotide exchange. The mutation accelerates dissociation of GDP from the alphai1beta1gamma2 heterotrimer by 250-fold. Nevertheless, affinity of mutant Gialpha1 for GTPgammaS is high in the presence of Mg2+, and the mutation has no effect on the intrinsic GTPase activity of the alpha subunit. The mutation also uncouples two activities of betagamma: stabilization of the GDP-bound alpha subunit (which is retained) and retardation of GDP dissociation from the heterotrimer (which is lost). For wild-type and mutant Gialpha1, beta gamma prevents irreversible inactivation of the alpha subunit at 30 degreesC. However, the mutation accelerates irreversible inactivation of alpha at 37 degreesC despite the presence of beta gamma. Structurally, the mutation weakens affinity for GTPgammaS by steric crowding: a 2-fold increase in the number of close contacts between the protein and the purine ring of the nucleotide. By contrast, we observe no differences in structure at the GDP binding site between wild-type heterotrimers and those containing A326S Gialpha1. However, the GDP binding site is only partially occupied in crystals of G protein heterotrimers containing A326S Gialpha1. In contrast to original speculations about the structural correlates of receptor-catalyzed nucleotide exchange, rapid dissociation of GDP can be observed in the absence of substantial structural alteration of a Galpha subunit in the GDP-bound state.     

Fame in the sciences: a culturomics approach

Scientometrics - Although scientists, like many other professionals, aspire to fame and recognition, research in the emergent field of fame and celebrity has as yet neglected to explore their fame...     

Sulfated glycolipids in ciliary body epithelium

The sulfated material which locates in the basal membrane of ciliary body epithelium when immature rat eyes are incubated with Na235SO4 was studied. On the basis of its chromatographic behavior compared with standard preparations, we conclude that the material consists of sulfatides.     

On the difference between active and nonactive role-playing methods.

J. Cooper (see record 1977-07138-001) is incorrect in assuming that involved participation is not possible in role-playing experiments. The distinction between role playing and role taking is illustrated through a reenactment of S. Milgram's (1963) mock learning experiment, using both the role-playing and the role-taking models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells

Esophageal adenocarcinoma (SKGT-2, SKGT-4, and SKGT-5) and epidermoid carcinoma (HCE-4) cells containing variable retinoblastoma (Rb), cyclin D1, p16, and p53 expression patterns were exposed to the synthetic flavone, flavopiridol. The IC50 was approximately 100-150 nM for each of these cell lines. Exposure of esophageal carcinoma cells to 300 nM flavopiridol induced cell cycle arrest and apoptosis, resulting in a 90% inhibition of proliferation relative to that of nontreated cells after a 5-day exposure to the drug. Western blot analysis revealed diminution of cyclin D1, Rb, and p107 protein levels after flavopiridol exposure. Whereas cell cycle arrest and overall growth inhibition did not correlate in any obvious manner with the genotype of these cell lines, apoptosis seemed to be more pronounced in SKGT-2 and SKGT-4 cells that lack Rb expression. Pretreatment of esophageal cancer cells with 9-cis-retinoic acid did not substantially potentiate flavopiridol activity in these cell lines. Although the precise mechanism of flavopiridol-mediated cytotoxicity has not been fully defined, this drug is an attractive agent for molecular intervention in esophageal cancers and their precursor lesions; further evaluation of flavopiridol in this clinical context is warranted.     

Reducing aflatoxin contamination in peanut genotypes by selection and breeding

The potential for developing agronomically suitable cultivais using peanut genotypes that exhibit resistance to seed colonization by aflatoxin-producing strains ofAspergillus species is explored. Some factors found to be associated with the nature of resistance to seed colonization by the toxin-producing fungi are cell structure, cell arrangement, permeability, waxy surface, tannin content and amino acid components of the seed testae. The practical implications of developing resistant cultivars are presented in data for yield, value and seed quality for 6 advanced peanut lines that were developed by breeding and selection from crosses.     

Structural mechanics of filamentous cyanobacteria

Filamentous cyanobacteria, forming long strands of connected cells, are one of the earliest and most successful forms of life on Earth. They exhibit self-organized behaviour, forming large-scale patterns in structures like biomats and stromatolites. The mechanical properties of these rigid structures have contributed to their biological success and are important to applications like algae-based biofuel production. For active polymers like these cyanobacteria, one of the most important mechanical properties is the bending modulus, or flexural rigidity. Here, we quantify the bending stiffness of three species of filamentous cyanobacteria, of order Oscillatoriales, using a microfluidic flow device where single filaments are deflected by fluid flow. This is complemented by measurements of Young’s modulus of the cell wall, via nanoindentation, and the cell wall thickness. We find that the stiffness of the cyanobacteria is well-captured by a simple model of a flexible rod, with most stress carried by a rigid outer wall. Finally, we connect these results to the curved shapes that these cyanobacteria naturally take while gliding, and quantify the forces generated internally to maintain this shape. The measurements can be used to model interactions between cyanobacteria, or with their environment, and how their collective behaviour emerges from such interactions.     

Economic welfare with exhaustible natural resources : A two-sector model with an ‘environmental’ commodity

A two-sector model of per capita utility is developed. The sectors are industrial (characterized by a Cobb—Douglas production function with technological change), and environmental (output proportionate to the amount of resources set aside from industry). The growing population contains identical individuals with Cobb— Douglas utility functions; each shares both outputs equally. It is shown that without technological change per capita utility must eventually fall due to resource exhaustion, even without population growth. Technological change can maintain constant or growing per capita utility through time, with the required rate depending on parameters of both production and utility functions.