Crystallization and preliminary X-ray crystallographic studies on a Kunitz-type potato serine protease inhibitor.

Interest in protease inhibitors has been renewed because of their potent activity in preventing carcinogenesis in a wide variety of in vivo and in vitro model systems. Potato tubers contain a wide range of such protease inhibitors. In cv. Elkana potato tubers, protease inhibitors represent about 50% of the total amount of soluble protein. Potato serine protease inhibitor (PSPI), one of the isoforms of the most abundant group of protease inhibitors, is a dimeric double-headed Kunitz-type inhibitor. No high-resolution structural information on this type of inhibitor has so far been obtained, as all currently known structures are of the monomeric single-headed or monomeric double-headed types. Crystals were grown in 0.1 M HEPES pH 7.5, 10% PEG 8000 and 8% ethylene glycol complemented with 9 mM 1-s-octyl-beta-D-thioglucoside or 0.1 M glycine. Data were collected from a single crystal under cryoconditions to 1.8 Å resolution. The protein crystallized in space group P21, with unit-cell parameters a = 54.82, b = 93.92, c = 55.44 Angstrom, beta = 100.7 °; the scaling Rsym is 0.044 for 45 456 unique reflections

Crystal structure of the DNA repair enzyme ultraviolet damage endonuclease

Biophysical Structural Chemistr

Crystal structure of chlorite dismutase, a detoxifying enzyme producing molecular oxygen

Biophysical Structural Chemistr

Traffic Grooming in Unidirectional WDM Rings with Bounded Degree Request Graph

Traffic grooming is a major issue in optical networks. It refers to grouping low rate signals into higher speed streams, in order to reduce the equipment cost. In SONET WDM networks, this cost is mostly given by the number of electronic terminations, namely ADMs. We consider the case when the topology is a unidirectional ring. In graph-theoretical terms, the traffic grooming problem in this case consists in partitioning the edges of a request graph into subgraphs with a maximum number of edges, while minimizing the total number of vertices of the decomposition. We consider the case when the request graph has bounded maximum degree $\Delta$, and our aim is to design a network being able to support any request graph satisfying the degree constraints. The existing theoretical models in the literature are much more rigid, and do not allow such adaptability. We formalize the problem, and solve the cases $\Delta=2$ (for all values of $C$) and $\Delta = 3$ (except the case C=4). We also provide lower and upper bounds for the general case

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe