Conservation of the centromere/kinetochore protein ZW10

Mutations in the essential Drosophila melanogaster gene zw10 disrupt chromosome segregation, producing chromosomes that lag at the metaphase plate during anaphase of mitosis and both meiotic divisions. Recent evidence suggests that the product of this gene, DmZW10, acts at the kinetochore as part of a tension-sensing checkpoint at anaphase onset. DmZW10 displays an intriguing cell cycle-dependent intracellular distribution, apparently moving from the centromere/kinetochore at prometaphase to kinetochore microtubules at metaphase, and back to the centromere/kinetochore at anaphase (Williams, B.C., M. Gatti, and M.L. Goldberg. 1996. J. Cell Biol. 134:1127-1140). We have identified ZW10-related proteins from widely diverse species with divergent centromere structures, including several Drosophilids, Caenorhabditis elegans, Arabidopsis thaliana, Mus musculus, and humans. Antibodies against the human ZW10 protein display a cell cycle-dependent staining pattern in HeLa cells strikingly similar to that previously observed for DmZW10 in dividing Drosophila cells. Injections of C. elegans ZW10 antisense RNA phenocopies important aspects of the mutant phenotype in Drosophila: these include a strong decrease in brood size, suggesting defects in meiosis or germline mitosis, a high percentage of lethality among the embryos that are produced, and the appearance of chromatin bridges at anaphase. These results indicate that at least some aspects of the functional role of the ZW10 protein in ensuring proper chromosome segregation are conserved across large evolutionary distances.     

Nitric oxide in renal health and disease

Nitric oxide (NO) is a labile radical gas that is widely acclaimed as one of the most important molecules in biology. Through covalent modifications of target proteins and redox reactions with oxygen and superoxide radical and transition metal prosthetic groups, NO plays a critical role in many vital biological processes, including the control of vascular tone, neurotransmission, ventilation, hormone secretion, inflammation, and immunity. Moreover, NO has been shown to influence a host of fundamental cellular functions, such as RNA synthesis, mitochondrial respiration, glycolysis, and iron metabolism. NO is formed from L-arginine by NO synthases (NOSs), a family of related enzymes encoded by separate unlinked genes. The different NOS isozymes exhibit disparate tissue and intrarenal distributions and are governed by unique regulatory mechanisms. In the kidney, NO participates in several vital processes, including the regulation of glomerular and medullary hemodynamics, the tubuloglomerular feedback response, renin release, and the extracellular fluid volume. While NO serves beneficial roles as a messenger and host defense molecule, excessive NO production can be cytotoxic, the result of NO's reaction with reactive oxygen and nitrogen species, leading to peroxynitrite anion formation, protein tyrosine nitration, and hydroxyl radical production. Indeed, NO may contribute to the evolution of several commonly encountered renal diseases, including immune-mediated glomerulonephritis, postischemic renal failure, radiocontrast nephropathy, obstructive nephropathy, and acute and chronic renal allograft rejection. Moreover, impaired NO production has been implicated in the pathogenesis of volume-dependent hypertension. This duality of NO's beneficial and detrimental effects has created extraordinary interest in this molecule and the need for a detailed understanding of NO biosynthesis.     

Understanding the implications of view update policies

Database views are traditionally described as unmaterialized queries, which may be coincidentally updatable according to some fixed criteria. One of the problems in updating through views lies in determining whether a given view modification can be correctly translated by the system. To define an updatable view, a view designer must be aware of how an update request in the view will be mapped into updates of the underlying relations. Furthermore, because of side effects, the view designer must also be made aware of the effects of isolated updates back into the view. To address this problem, we present a general algorithm that predicts the effects of arbitrary mapping policies. Given an update policy, this algorithm indicates whether a desired update will, in fact, occur in the view and describes all possible side effects it may have, documenting the conditions under which they occur. The algorithm subsumes the results obtained by other view design tools, and generalizes their use to encompass a larger class of views.     

Hawaiian and Azorean volcanic aggregates: a preliminary study of the potential alkali-silica reaction

Bulletin of Engineering Geology and the Environment - The alkali-silica reaction (ASR) is a chemical deterioration of concrete that involves reactive forms of silica. Volcanic glass is one of the...     

Structural,Electrical, Mechanical,and Thermal Properties of Electrospun Poly(lactic acid)/Polyaniline Blend Fibers

Conducting electrospun fiber mats based on PLA and PAni blends were obtained with average diameter values between 87 and 1 006 nm with PAni quantities from 0 to 5.6 wt.‐%. Structural characteristics of fiber mats were compared to cast films with the same amount of PAni and studied by SEM, SAXS, and AFM. Thermal properties of fiber mats and cast films were compared by DSC analyses. Mechanical properties of fiber mats were also evaluated. It was found that electrospinning process governs the crystal structure of the fibers and strongly affects fiber properties. New properties of PLA/PAni blends are reported due to the size fiber reduction.

     

Structural modeling of the pro-ocytocin-neurophysin precursor

The hormonal precursor pro-ocytocin-neurophysin is activated by selective cleavage at Arg2-Ala13, producing mature ocytocin and neurophysin. To understand the cleavage mechanism better, and in particular the recognition of the cleavage site, it is necessary to characterize the three-dimensional structure of the precursor molecule. Here we combine a variety of experimental data with molecular modeling and dynamics calculations to derive possible precursor conformations. In the models obtained, the N-terminus of the precursor, corresponding to the ocytocin segment, is hydrogen bonded in a pocket of the neurophysin moiety in a similar manner to a crystallographically obtained non-covalent complex between the two molecules. The calculations suggest that although the ocytocin segment is relatively flexible, it adopts a stable, broad loop structure in the vicinity of the cleavage region, which may constitute the structural element recognized by the cleaving enzyme. The calculations also suggest a possible widening of the distance between the two neurophysin domains in the precursor relative to that in the non-covalent neurophysin- ocytocin complex.