Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Spring 2014

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Summer 2014

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Fall 2014

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Winter 2014

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Spring 2015, vol. 27, no.1

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Reply to the letter to the editor "Freedom of choice".

Réponse au commentaire de: Gnädinger M. Freedom of choice. Swiss Med Wkly. 2012 Mar 22;142:0. doi:10.4414/smw.2012.13527. PMID: 22441992.

Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase.

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.

Boosting Future Prospects or Softening Promises of Success? The Use of Emphatics and Hedging in the Letter to Shareholders Sections of Annual Reports

Tämä pro gradu -tutkielma käsittelee yritysten vuosikertomusten Toimitusjohtajan katsaus -osioissa esiintyvää metatekstiä. Erityisenä tutkimuskohteena ovat yrityksen tulevaisuutta käsittelevät lauseet ja niissä käytetty interpersonaalinen metateksti, jonka avulla kirjoittaja pyrkii joko vahvistamaan (emphatics-keinoin) tai heikentämään (hedging-keinoin) ilmaisujensa vahvuutta ja lukijalle niiden kautta välittyvää kuvaa viestin varmuudesta ja vakuuttavuudesta. Sijoittajille suunnattu Toimitusjohtajan katsaus käsittelee yleensä yrityksen edellisen vuoden tulosta, taloudellista asemaa sekä tulevaisuudennäkymiä. Tutkimuksen tarkoituksena oli selvittää, vaikuttaako yrityksen taloudellinen menestys vuosikertomuksen tässä osiossa käytetyn metatekstin määrään ja laatuun. Tutkimuksen teoriaosuudessa käsitellään ensiksi lyhyesti vuosikertomuksia ja niiden parissa tehtyä aiempaa kielitieteellistä tutkimusta, minkä jälkeen perehdytään tarkemmin metatekstin sekä hedging- ja emphatics-keinojen määrittelyyn. Näissä osioissa apuna toimivat muunmuassa Hylandin (1998) ja Cromptonin (1997) tutkimukset. Tutkimusaineistossa esiintyvien metatekstilajien määrittelyssä ja tunnistamisessa käytettiin apuna pääosin Crismore & Farnsworthin (1990) ja Grabe & Kaplanin (1997) tutkimuksia. Tutkimuksen aineistona oli yhteensä 23 yhdentoista amerikkalaisen yrityksen vuosikertomusta. Ne käsittivät esimerkkejä kunkin yhtiön talouden kannalta sekä erityisen hyviltä että huonoilta vuosilta. Aineistosta löydetty interpersonaalinen metateksti luokiteltiin viiteen eri ryhmään: modaaliverbit, hedging-verbit, muut hedging-keinot, emphatics-keinot ja evaluatives-keinot (eli kirjoittajan tekstistään tekemät subjektiiviset huomiot ja arviot). Tulokset osoittivat, että metatekstin käytössä ilmeni melkoista vaihtelua yksittäisten yritysten ja niiden hyvien ja huonojen vuosien välillä. Nämä eroavuudet eivät kuitenkaan vaikuttaneet merkittävästi koko aineiston kattaviin keskivertolukuihin, joiden avulla pyrittiin selvittämään hyvien ja huonojen vuosien välisiä yleisiä eroja. Tutkimuksen perusteella voidaan todeta, että Toimitusjohtajan katsaus –osioiden viittaukset yhtiön tulevaisuuteen heijastavat tavallisesti kirjoittajan varmuutta yrityksen menestyksekkäästä tulevaisuudesta riippumatta siitä, minkälainen vuosikertomuksessa käsitelty vuosi on ollut yhtiölle taloudellisesti. Yleisesti ottaen yhtiön taloudellisen tilan ei siis havaittu vaikuttavan Toimitusjohtajan katsauksessa käytetyn metadiskurssin määrään tai laatuun.

Identification of the divergent calmodulin binding motif in yeast Ssb1/Hsp75 protein and in other HSP70 family members

Yeast soluble proteins were fractionated by calmodulin-agarose affinity chromatography and the Ca2+/calmodulin-binding proteins were analyzed by SDS-PAGE. One prominent protein of 66 kDa was excised from the gel, digested with trypsin and the masses of the resultant fragments were determined by MALDI/MS. Twenty-one of 38 monoisotopic peptide masses obtained after tryptic digestion were matched to the heat shock protein Ssb1/Hsp75, covering 37% of its sequence. Computational analysis of the primary structure of Ssb1/Hsp75 identified a unique potential amphipathic alpha-helix in its N-terminal ATPase domain with features of target regions for Ca2+/calmodulin binding. This region, which shares 89% similarity to the experimentally determined calmodulin-binding domain from mouse, Hsc70, is conserved in near half of the 113 members of the HSP70 family investigated, from yeast to plant and animals. Based on the sequence of this region, phylogenetic analysis grouped the HSP70s in three distinct branches. Two of them comprise the non-calmodulin binding Hsp70s BIP/GR78, a subfamily of eukaryotic HSP70 localized in the endoplasmic reticulum, and DnaK, a subfamily of prokaryotic HSP70. A third heterogeneous group is formed by eukaryotic cytosolic HSP70s containing the new calmodulin-binding motif and other cytosolic HSP70s whose sequences do not conform to those conserved motif, indicating that not all eukaryotic cytosolic Hsp70s are target for calmodulin regulation. Furthermore, the calmodulin-binding domain found in eukaryotic HSP70s is also the target for binding of Bag-1 - an enhancer of ADP/ATP exchange activity of Hsp70s. A model in which calmodulin displaces Bag-1 and modulates Ssb1/Hsp75 chaperone activity is discussed.

Transduction motif analysis of gastric cancer based on a human signaling network

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR,MAPK14, BCL2L1, KRT18,PTPN6, CASP3, TGFBR2,AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Letter from the acting Secretary of War, transmitting information relative to the claims of the State of Massachusetts for payment of the expenses of the militia ordered out by the executive authority of the state, during the late war. --

15th Congress, 1st session, 1817-1818, House. Doc. 81.