Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB.

CREB is a cAMP-responsive nuclear DNA-binding protein that binds to cAMP response elements and stimulates gene transcription upon activation of the cAMP signalling pathway. The protein consists of an amino-terminal transcriptional transactivation domain and a carboxyl-terminal DNA-binding domain (bZIP domain) comprised of a basic region and a leucine zipper involved in DNA recognition and dimerization, respectively. Recently, we discovered a testis-specific transcript of CREB that contains an alternatively spliced exon encoding multiple stop codons. CREB encoded by this transcript is a truncated protein lacking the bZIP domain. We postulated that the antigen detected by CREB antiserum in the cytoplasm of germinal cells is the truncated CREB that must also lack its nuclear translocation signal (NTS). To test this hypothesis we prepared multiple expression plasmids encoding carboxyl-terminal deletions of CREB and transiently expressed them in COS-1 cells. By Western immunoblot analysis as well as immunocytochemistry of transfected cells, we show that CREB proteins truncated to amino acid 286 or shorter are sequestered in the cytoplasm, whereas a CREB of 295 amino acids is translocated into the nucleus. Chimeric CREBs containing a heterologous NTS fused to the first 248 or 261 amino acids of CREB are able to drive the translocation of the protein into the nucleus. Thus, the nine amino acids in the basic region involved in DNA recognition between positions 287 and 295 (RRKKKEYVK) of CREB contain the NTS. Further, mutation of the lysine at position 290 in CREB to an asparagine diminishes nuclear translocation of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Translocation of cyanogenic glycosides in rubber tree crown clones resistant to South American leaf blight

The objective of this work was to assess the possible transport of cyanogenic glycosides from leaves of rubber tree crown clones (Hevea spp.) resistant to South American leaf blight to the trunk of the panel clones in which they are grafted. The cyanogenic potential (HCNp) of the crown clones was determined in the trunk bark, at different distances from the cambium, and its gradient was evaluated along the trunk. The correlation between the HCNp of the crown leaves and that of the trunk bark was also evaluated. HCNp determined in leaves showed a wide range variation in the species studied as crown clones, with the lowest values registered in H. nitida clones, and the highest ones in H. rigidifolia. In the trunk bark, the tissue layer nearer the cambium showed higher HCNp values. A positive basipetal gradient was observed along the trunk, i.e., there was an increase in HCNp from the apex toward the base. Although the grafted crowns influence the cyanogenic potential of the trunk bark of panel clones, the absence of correlation between the HCNp of the leaves and trunk bark indicates that the crown is not the main source of the cyanogenic glycosides found in the trunk.

Generating a raster map presentation of a forest resource by solving a transportation problem

Abstract

Prepupal Building Behavior in Drosophila melanogaster and Its Evolution under Resource and Time Constraints.

Structures built by animals are a widespread and ecologically important 'extended phenotype'. While its taxonomic diversity has been well described, factors affecting short-term evolution of building behavior within a species have received little experimental attention. Here we describe how, given the opportunity, wandering Drosophila melanogaster larvae often build long tunnels in agar substrates and embed their pupae within them. These embedded larvae are characterized by a longer egg-to-pupariation developmental time than larvae that pupate on the surface. Assuming that such building behaviors are likely to be energetically costly and/or time consuming, we hypothesized that they should evolve to be less pronounced under resource or time limitation. In accord with this prediction, larvae from populations evolved for 160 generations under a regime that combines larval malnutrition with limited developmental time dug shorter tunnels than larvae from control unselected populations. However, the proportion of larvae that embedded before pupation did not differ between the malnutrition-adapted and control populations, suggesting that tunnel length and likelihood of embedding before pupation are controlled by different genetic loci. The behaviors exhibited by wandering larvae of Drosophila melanogaster prior to pupation offer a model system to study evolution of animal building behaviors because the tunneling and embedding phenotypes are simple, facultative and highly variable.

Cervical nerve root synovial sarcoma in a child with chromosomal (X;18) translocation. Case report and review of the literature.

We report on an 11-year-old female with a history of cervicobrachialgia and progressive weakness of the right arm. Cervical spine MRI showed an enhancing heterogeneous intradural mass occupying the right C6-C7 foramen. She underwent a right C6-C7 foraminotomy with a complete macroscopic removal of the lesion. Pathological examination revealed a synovial sarcoma. Treatment was completed by chemotherapy and proton radiotherapy, and the girl remained free of symptoms for 3 years. After appearance of new symptoms, a local recurrence was confirmed, and despite aggressive treatment with salvage chemotherapy and radiotherapy, the disease progressed beyond medical control, and the child died, 6 years after diagnosis. Early recognition of this rare entity compared to its more benign differential diagnosis is crucial, as an aggressive management is needed.

Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics

Purpose: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was 1,407 ( 897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.

Resource-based approach to new product development at the intersection of industries. Two case studies in telecommunications

Työn tavoitteena on selvittää mitkä ovat tärkeimmät aineettomat resurssit, joita tarvitaan teollisuuksien risteyskohdassa tapahtuvassa tuotekehityksessä. Teollisuuksien risteyskohdissa syntyvät tuotteet ovat usein radikaaleja, mikä tekee tuotteista mielenkiintoisia, paljon liiketoimintapotentiaalia tarjoavia. Tämä tutkimus lähestyy tuotekehitystä resurssipohjaisesta näkökulmasta. Myös tietämyspohjaista ja suhdepohjaista näkemystä hyödynnetään korostamaan keskittymistä aineettomiin resursseihin. Tutkimuksessa rakennetaan viitekehys, jossa tutkitaan eri resurssikategorioita. Valitut kategoriat ovat teknologiset, markkinointi-, johtamiseen ja hallinnointiin liittyvät ja suhdepohjaiset resurssit. Empiirisessä osassa tutkitaan kahta uutta tuotekonseptia, jotka ovat syntyneet teollisuuksien risteyskohdissa. Empiirisen osan tavoitteena on määritellä tutkimuksen kohteena olevia alustavia tuotekonsepteja tarkemmin ja selvittää millaisia resursseja näiden toteuttamiseen tarvitaan. Myös tarvittavien resurssien nykytila selvitetään ja pohditaan tulisiko puuttuvia resursseja kehittää yrityksen sisällä vai hankkia ne ulkopuolelta. Tutkimus toteutettiin asiantuntijahaastatteluin. Kahden tapaustutkimuksen perusteella näyttäisi siltä, että suhdepohjaiset resurssit ovat erittäin tärkeitä teollisuuksien risteyskohdissa tapahtuvassa tuotekehityksessä. Myös teknologiset resurssit ovat tärkeitä. Markkinointiresurssien tärkeys riippuu lopullisesta tuotekonseptista, kun taas johtamiseen ja kehittämiseen liittyvät resurssit ovat tärkeitänäiden konseptien luomisessa.

Trophic resource partitioning and competition between the two sibling bat species Myotis myotis and Myotis blythii

1. Niche theory predicts that the stable coexistence of species within a guild should be associated, if resources are limited, with a mechanism of resource partitioning. Using extensive data on diets, the present study attempts: (i) to test the hypothesis that, in sympatry, the interspecific overlap between the trophic niches of the sibling bat species Myotis myotis and M. blythii-which coexist intimately in their roosts-is effectively lower than the two intraspecific overlaps; (ii) to assess the role played by interspecific competition in resource partitioning through the study of trophic niche displacement between several sympatric and allopatric populations. 2. Diets were determined by the analysis of faecal samples collected in the field from individual bats captured in various geographical areas. Trophic niche overlaps were calculated monthly for all possible intraspecific and interspecific pairs of individuals from sympatric populations. Niche breadth was estimated from: (i) every faecal sample; (ii) all the faecal samples collected per month in a given population (geographical area). 3. In every population, the bulk of the diets of M. myotis and M. blythii consisted of, respectively, terrestrial (e.g. carabid beetles) and grass-dwelling (mostly bush crickets) prey. All intraspecific trophic niche overlaps were significantly greater than the interspecific one, except in Switzerland in May when both species exploited mass concentrations of cockchafers, a non-limiting food source. This clearcut partitioning of resources may allow the stable, intimate coexistence observed under sympatric conditions. 4. Relative proportions of ground-and grass-dwelling prey, as well as niche breadths (either individual or population), did not differ significantly between sympatry and allopatry, showing that, under allopatric conditions, niche expansion does not take place. This suggests that active interspecific competition is not the underlying mechanism responsible for the niche partitioning which is currently observed between M. myotis and M. blythii.

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule.

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.

UniPathway: a resource for the exploration and annotation of metabolic pathways.

UniPathway (http://www.unipathway.org) is a fully manually curated resource for the representation and annotation of metabolic pathways. UniPathway provides explicit representations of enzyme-catalyzed and spontaneous chemical reactions, as well as a hierarchical representation of metabolic pathways. This hierarchy uses linear subpathways as the basic building block for the assembly of larger and more complex pathways, including species-specific pathway variants. All of the pathway data in UniPathway has been extensively cross-linked to existing pathway resources such as KEGG and MetaCyc, as well as sequence resources such as the UniProt KnowledgeBase (UniProtKB), for which UniPathway provides a controlled vocabulary for pathway annotation. We introduce here the basic concepts underlying the UniPathway resource, with the aim of allowing users to fully exploit the information provided by UniPathway.

The Boundaries of a Firm in the Pulp and Paper Industry: Complementarities of the Resource-Based View and Transaction Cost Economics

Tämän tutkimuksen tarkoituksena on tutkia sellu- ja paperiteollisuuden toimintojen luonnetta sekä miten yrityksen rajapinnat ovat muodostuneet ko. teollisuudenalalla. Tutkimus on eksploratiivinen ja luonteeltaan kvalitatiivinen. Tutkimuksen aineisto kerättiin yrityksissä tehdyillä teemahaastatteluilla. Sellu- ja paperitehtaan toimintojen analysoinnissa käytetään resurssiperusteista näkemystä ja transaktiokustannusteoriaa. Tutkimuksen yritysten rakennetta voidaan pitää varsin konservatiivisena. Teoreettinen kehys pystyi selittämään varsinaisen tuotannon järjestämistä varsin hyvin. Tukitoiminnoissa löytyi ristiriitoja teorian ja todellisuuden välillä. Tuotantotoiminnot kannattaa pitää yrityksen sisällä, koska ne täyttävät VRIN-attribuutit ja niihin liittyy korkeita transaktiokustannuksia. Suurin osa tukitoiminnoista voidaan luokitella triviaaleiksi. Joitain tukitoimintoja voidaan kuitenkin luokitella strategisesti tärkeiksi, ja voidaan päätellä, että ne pitäisi pitää yrityksen sisällä. Tässä suhteessa tulokset olivat kuitenkin ristiriitaisia, ja lisätutkimuksia tarvittaisiin lopullisten johtopäätösten tekemiseen.

The Reflections of Strategic Orientation on profitability - A resource-based study in pulp and paper industry

Tutkielman tavoitteena oli analysoida erilaisia strategisia orientaatioita sellu- ja paperiteollisuudessa. Sellu- ja paperiteollisuus on kohtaamassa strategisia haasteita, jotka ulottuvat syvälle sen rakenteisiin. Yritykset ovat valinneet erilaisia lähestymistapoja organisoidessaan tuotantoa ja kansainvälistä arvoketjuaan tässä muuttuvassa ympäristössä. Tutkimukseen valittiin 30 suurinta sellu- ja paperiteollisuudessa toimivaa yritystä ja mahdollisia syitä kannattavuuseroihin yritysten välillä analysoitiin. Yritysten strategista orientaatiota tarkasteltiin vertailemalla muun muassa seuraavia tekijöitä: vertikaalinen integraatioaste, tuotevalikoiman laajuus, tuotantokapasiteetin levinneisyys ja tuotantokapasiteetin ikä. Kannattavuutta mitattiin erilaisilla talouden tunnusluvuilla (liikevoitto, oman pääoman tuotto-%, koko pääoman tuotto-%). Tulosten mukaan yrityksiä voidaan ryhmitellä strategisen orientaation perusteella ja ryhmien välillä on kannattavuuseroja.

From the Resource-Base to Firm Boundaries in the Electricity Network Business - Case Lappeenrannan Energia Oy

Tutkielman tavoitteena oli selvittääcase -yrityksen resurssi- ja kyvykkyyspohjaa resurssiperustaisen näkemyksen mukaan, sekä yrityksen rajoja transaktiokustannusteorian mukaan. Tutkimusongelmia lähestyttiin kirjallisuuskatsauksella, puoli-strukturoiduilla teemahaastatteluilla, sekä kyselylomakkeilla. Tutkielman päätuloksiksi voidaan Tukea löydetty resurssikuilu, resurssien ja kyvykkyyksien tutkinta, sekä kyselylomakkeiden rakentaminen ja käyttö. Tutkielman paljastamasta kuilusta voidaan erottaa kolme päähaastetta; ikääntyvät sähköverkot, ikääntyvä henkilökunta ja liiketoimintaosaamisen puute. Lisäksi resurssien ja kyvykkyyksien tutkinta nosti esille organisaation rutiineja ja prosesseja, ja kyselylomakkeet osoittautuivat varsin toimiviksi tutkimuksen kontekstissa. Yhteenvetona voidaan todeta, että sähköverkkoliiketoiminta ja case yritys ovat suuren rakennemuutoksen alla, joka tuo mukanaan suuria haasteita myös lähitulevaisuudessa.

Sexual dimorphism in a dioecious population of the wind-pollinated herb Mercurialis annua: the interactive effects of resource availability and competition.

Background and Aims Male-biased sex allocation commonly occurs in wind-pollinated hermaphroditic plants, and is often positively associated with size, notably in terms of height. Currently, it is not well established whether a corresponding pattern holds for dioecious plants: do males of wind-pollinated species exhibit greater reproductive allocation than females? Here, sexual dimorphism is investigated in terms of life history trade-offs in a dioecious population of the wind-pollinated ruderal herb Mercurialis annua.Methods The allocation strategies of males and females grown under different soil nutrient availability and competitive (i.e. no, male or female competitor) regimes were compared.Key Results Male reproductive allocation increased disproportionately with biomass, and was greater than that of females when grown in rich soils. Sexual morphs differentially adjusted their reproductive allocation in response to local environmental conditions. In particular, males reduced their reproductive allocation in poor soils, whereas females increased theirs, especially when competing with another female rather than growing alone. Finally, males displayed smaller above-ground vegetative sizes than females, but neither nutrient availability nor competition had a strong independent effect on relative size disparities between the sexes.Conclusions Selection appears to favour plasticity in reproductive allocation in dioecious M. annua, thereby maintaining a relatively constant size hierarchy between sexual morphs. In common with other dioecious species, there seems to be little divergence in the niches occupied by males and females of M. annua.