High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

Investigation of Founder Effects for the Thr377Met Myocilin Mutation in Glaucoma Families from Differing Ethnic Backgrounds

Purpose: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. Methods: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. Results: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. Conclusions: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies

Bovine Somatotropin Alters Myosin Heavy Chains and Beta Receptors in Skeletal Muscle of Feedlot Heifers with Little Impact on Live or Carcass Performance

The objective was to determine whether recombinant bovine somatotropin (rbST) enhanced live performance,skeletal muscle biological activity, and beta-adrenergic receptor expression of feedlot heifers during the finishing phase. Heifers (n = 16; initial body weight = 457 ± 3 kg) were randomly assigned to pens (4 pens/treatment; 2 heads/pen) and treatment: (1) no rbST (Control); (2) 500 mg/hd of sometribove zinc at day 0 and 14 (rbST; Posilac®; Elanco AnimalHealth, Greenfield, IN). Longissimus muscle biopsies for muscle chemistry were collected on day 0, 14, 28, 42, and 56. The rbST heifers had increased expression of AMP-activated protein kinase alpha and beta 3 adrenergic receptor (P < 0.05). Day of the study affected the expression of myosin heavy chain-IIA (MHC-IIA), MHC-IIX, beta 2 adrenergic receptor, peroxisome proliferator-activated receptor gamma, and stearoyl-CoA desaturase (P < 0.05). Day had a significant effect on muscle fiber cross-sectional area and proportion (P < 0.05). As days on feed increased, the area of MHC-I fibers decreased whereas MHC-IIA and IIX area increased (P < 0.05). The rbST heifers had decreased proportions of MHC-I fibers and increased proportions of MHC-IIX fibers (P < 0.05). The greatest density of Paired Box 7-positive cells was on day 0, 28, and 42 (P < 0.05), and the greatest density of Myogenic factor 5-positive cells was on day 42 and 56 (P < 0.05). Also, the greatest density of cells positive for Paired Box 7:Myogenic factor 5 was measured on day 28 (P < 0.05). These data indicate that, as days on feed increase, the effects of skeletal muscle biological activity are not dependent on rbST administration but may be more due to physiological changes occurring as the animal reaches physio-logical maturity

Exile Vol. XXXI No. 1

Drawing by Chris Bradley 1 How Goes the Wombat, Prithee by Jennie Benford 3 Holy Shit (for Mary) by Stephanie Athey 4-5 ..... blues by Britton R. Creelman 6 Photograph (anonymous) 7 Prose by Leigh Walton 9-12 San Jacinto by Petersen S. Thomas 13 Rebuttal by Betsy Oster 15 Running Alone by Ann Townsend McMullen 16 Windows in Florence by Michael Parr 17 Rangers by Caroline Palmer 19 Salamapo by Mary Deborah Clark 20-21 Funeral by J. K. Rand 22 Deeds Give No Title by Douglas Jones 23 Be Careful, There\u27s a Straight Bar Next Door by Karen J. Hall 25 The Rivers of Saigon by Alex Dickson 26 2 Sketches by Alfred Sturla Bodvarsson 27 Upon the Occasion of Reading 236 sonnets at One Sitting by Jeff Masten 28 I just believe in Me by Rob Jackson 29 Close by Stephanie Athey 31 Teller by Katherine Fox Reynolds 32 Woman in Greece by Michael Parr 33 Part of the Job by Joan DeWitt 35-44 Contributor Notes 46 Editorial decision is shared equally among the seven member editorial board. -title page Polymorphous: Cover Lithograph by Aimee Creelman - title pag

Detailed Pilots Specification

The Electronic Archiving Service consists of a series of activities covered by software tools and manual workflow steps. These tools are currently partly in existence, some are being developed by E-ARK project, many more are to be added by developments of the digital preservation community in the future. The role of this report is to identify the most relevant scenarios for the E-ARK Service, define which scenario which level of activity is needed in order to bridge the gap of the currently existing solutions (e.g. integration, software development, interface definition

Documentation, Common Information and Short Overview of the E-ARK pilots

This report contains the common information and short overview of the pilots, along with references to the final version of the Pilot Definition Excel files and Pilot Documentation Packages

Chemical structure-guided design of dynapyrazoles, potent cell-permeable dynein inhibitors with a unique mode of action

Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition