Deletion mutants in COP9/Signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes

The COP9/signalosome complex is highly conserved in evolution and possesses significant structural similarity to the 19S regulatory lid complex of the proteasome. It also shares limited similarity to the translation initiation factor eIF3. The signalosome interacts with multiple cullins in mammalian cells. In the fission yeast Schizosaccharomyces pombe, the Csn1 subunit is required for the removal of covalently attached Nedd8 from Pcu1, one of three S. pombe cullins. It remains unclear whether this activity is required for all the functions ascribed to the signalosome. We previously identified Csn1 and Csn2 as signalosome subunits in S. pombe. csn1 and csn2 null mutants are DNA damage sensitive and exhibit slow DNA replication. Two further putative subunits, Csn4 and Csn5, were identified from the S. pombe genome database. Herein, we characterize null mutations of csn4 and csn5 and demonstrate that both genes are required for removal of Nedd8 from the S. pombe cullin Pcu1 and that their protein products associate with Csn1 and Csn2. However, neither csn4 nor csn5 null mutants share the csn1 and csn2 mutant phenotypes. Our data suggest that the subunits of the signalosome cannot be considered as a distinct functional unit and imply that different subunits of the signalosome mediate distinct functions

PyFR: An Open Source Framework for Solving Advection-Diffusion Type Problems on Streaming Architectures using the Flux Reconstruction Approach

High-order numerical methods for unstructured grids combine the superior accuracy of high-order spectral or finite difference methods with the geometric flexibility of low-order finite volume or finite element schemes. The Flux Reconstruction (FR) approach unifies various high-order schemes for unstructured grids within a single framework. Additionally, the FR approach exhibits a significant degree of element locality, and is thus able to run efficiently on modern streaming architectures, such as Graphical Processing Units (GPUs). The aforementioned properties of FR mean it offers a promising route to performing affordable, and hence industrially relevant, scale-resolving simulations of hitherto intractable unsteady flows within the vicinity of real-world engineering geometries. In this paper we present PyFR, an open-source Python based framework for solving advection-diffusion type problems on streaming architectures using the FR approach. The framework is designed to solve a range of governing systems on mixed unstructured grids containing various element types. It is also designed to target a range of hardware platforms via use of an in-built domain specific language based on the Mako templating engine. The current release of PyFR is able to solve the compressible Euler and Navier-Stokes equations on grids of quadrilateral and triangular elements in two dimensions, and hexahedral elements in three dimensions, targeting clusters of CPUs, and NVIDIA GPUs. Results are presented for various benchmark flow problems, single-node performance is discussed, and scalability of the code is demonstrated on up to 104 NVIDIA M2090 GPUs. The software is freely available under a 3-Clause New Style BSD license (see www.pyfr.org)

Stochastic Index Numbers: A Review

The stochastic approach is a new way of viewing index numbers in which uncertainty and statistical ideas play a central role. Rather than just providing a single number for the rate of inflation, the stochastic approach provides the whole probability distribution of inflation. This paper reviews the key elements of the approach and then discusses some previously overlooked links with Fisher’s early work contained in his book The Making of Index Numbers. We then consider some more recent developments, including Diewert’s well-known critique of the stochastic approach, and provide responses to his criticisms. We also provide a review of Theil’s work on the stochastic approach, and present and extend Diewert’s work on this topic within the context of the Country Product Dummy method which measures price levels internationally.

Performance of grade and crossbred ewes

Tennessee is predominantly a milk-fat spring lamb production area with some purebred production. These lambs are produced primarily by mating either native, western crossbred or fine-wool grade ewes to pure bred rams of mutton type, from the Hampshire, Suffolk and Southdown breeds. In the past, milk-fat spring lamb producers have preferred to sell their ewe lambs and to buy their replacement ewes from western sources rather than produce home-raised replacements. In general. western yearling ewes ready for breeding are less infected with parasites and can be obtained in large groups of uniform type, age, breed and size as compared to native ewes or home-raised replacements. In recent years, however, it has become increasingly more difficult to obtain western ewes of the desired breeding and quality. This has led many producers to consider the possibility of saving replacements from within the flock and has raised questions regarding the performance of ewes of grade and crossbred breeding, and various systems which might be used in producing replacement ewes. Breeding or inherent genetic producing ability has economic significance to the producer for greater and more efficient production of lamb and wool. Both the breed of sire and breeding of the dam are important factors in producing lambs with superior growth and meat qualities. The qualities required in ewes for superior productivity are thriftiness, high prolificacy, good mothering ability, high milk production and satisfactory wool production. Ewes must produce a high percentage of twins with sufficient vigor to assure a high percentage of survival. Grading up flocks from native or crossbred foundations or the use of a rotational crossbreeding program would offer two possibilities to the producer for producing replacement ewes. Crossbreeding to improve market lamb production has been a major practice in the sheep industry of this country for many years. The pattern of crossbreeding differs considerably from section to section depending upon the environment and type of pasture and other conditions in the area. Planned crossbreeding is used mainly to evolve a type of sheep which is adapted to the particular environmental and economic conditions of the area. Studies have shown that crossbreeding increases fertility and prolificacy in ewes and livability in lambs. Three- and fo-ur-breed crosses have generally been superior in performance to purebreds, grades and two-breed crosses in terms of overall productivity. Previous research at the Tennessee Experiment Station has shown that the Northwestern crossbred Hampshire x Rambouillet ewe has performed well under Tennessee conditions, and superior in most respects to native ewes of mutton breeding. The grade Rambouillet ewe, although not as prolific as the Hampshire x Rambouillet ewe has also demonstrated certain advantages under Tennessee conditions. The purposes of this study were: (l) to evaluate the performance and adaptability of high-grade and 2-breed and 3-breed crosses for spring lamb production; (2) to investigate the feasibility of producing stock replacement ewes within a flock, as compared to purchasing the ewes available from other sources; (3) to study the effectiveness of performance selection methods in improving productivity; and (4) to study the reproductive behavior and performance of commercial types of sheep

Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.

Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the polymerase and ligase reactions respectively. PNK binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain. We show here, contrary to previous studies, that the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes