Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background.

Two new species of Loricariidae (Teleostei: Siluriformes) from main channels of the upper and middle Amazon Basin, with discussion of deep water specialization in loricariids

Hemiancistrus pankimpuju, new species, and Panaque bathyphilus, new species, are described from the main channel of the upper (Maranon) and middle (Solimoes)Amazon River, respectively. Both species are diagnosed by having a nearly white body, long filamentous extensions of both simple caudal-fin rays, small eyes, absence of an iris operculum and unique combinations of morphometrics. The coloration and morphology of these species, unique within Loricariidae, are hypothesized to be apomorphies associated with life in the dark, turbid depths of the Amazon mainstem. Extreme elongation of the caudal filaments in these and a variety of other main channel catfishes is hypothesized to have a mechanosensory function associated with predator detection.

A new species of Cycloramphus Tschudi (Anura: Cycloramphidae) from the Parque Nacional da Serra dos Orgaos, Southeastern Brazil

We report here the discovery of a new species of frog associated to the open areas of the highlands of the Parque Nacional da Serra dos Orgaos. The new species, Cycloramphus organensis is characterized by a unique skin texture, medium size ( maximum male and female SVL 26.4 mm and 33.3 mm respectively), dorsal surfaces uniformly brick red colored, uniformly areolate skin on dorsum, pupil horizontal, iris with a menisc on upper margin; no fleshy tubercles on eyelid, tympanic annulus concealed beneath skin, macroglands not visible externally, fingers and toes without fringes and webs; supernumerary palmar and plantar tubercles absent, nuptial spines absent. Despite the presence of an iris menisc, a character shared by frogs of both genera Cycloramphus and Zachaenus Cope, the combination of morphological characters is so unique that the allocation of the species to any of these genera remains ambiguous. Consequently, we used additional molecular-based phylogenetic analyses to ascertain the position of the new taxon. The new species proved to be embedded within the genus Cycloramphus.

Investigation by Combined Solid-State NMR and SAXS Methods of the Morphology and Domain Size in Polystyrene-b-Polyethylene Oxide-b-Polystyrene Triblock Copolymers

The microphase structure of a series of polystyrene-b-polyethylene oxide-b-polystyrene (SEOS) triblock copolymers with different compositions and molecular weights has been studied by solid-state NMR, DSC, wide and small angle X-ray scattering (WAXS and SAXS). WAXS and DSC measurements were used to detect the presence of crystalline domains of polyethyleneoxide (PEO) blocks at room temperature as a function of the copolymer chemical composition. Furthermore, DSC experiments allowed the determination of the melting temperatures of the crystalline part of the PEO blocks. SAXS measurements, performed above and below the melting temperature of the PEO blocks, revealed the formation of periodic structures, but the absence or the weakness of high order reflections peaks did not allow a clear assessment of the morphological structure of the copolymers. This information was inferred by combining the results obtained by SAXS and (1)H NMR spin diffusion experiments, which also provided an estimation of the size of the dispersed phases of the nanostructured copolymers. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48:55-64,2010

Hydrolytic Activity of Free and Immobilized Cellulase

Cellulase is an enzymatic complex which synergically promotes the degradation of cellulose to glucose. The adsorption behavior of cellulase from Trichoderma reesei onto Si wafers or amino-terminated surfaces was investigated by means of ellipsometry and atomic force microscopy (AFM) as a function of temperature. Upon increasing temperature from (24 +/- 1) to (60 +/- 1) degrees C, adsorption of cellulase became faster and more pronounced and the mean roughness of cellulase adsorbed layers increased. In the case of cellulase adsorbed onto Si wafers, Arrhenius`s plot allowed us to estimate the adsorption energy as 24.2 kJ mol(-1). The hydrolytic activity of free cellulase and cellulase immobilized onto Si wafers was tested using cellulose dispersions as substrates. The incubation temperature ranged from (37 +/- 1) to (60 +/- 1) degrees C. The highest efficiency was observed at (60 +/- 1) degrees C. The amount of glucose produced by free cellulase was similar to 20% higher than that obtained from immobilized cellulase. However, immobilizing cellulase onto Si wafers proved to be advantageous because they could be reused six times while retaining their original activity level. Such an effect was attributed to surface hydration, which prevents enzyme denaturation. The hydrolytic activity of cellulase immobilized onto amino-terminated surfaces was slightly lower than that observed for cellulase adsorbed onto Si wafers, and reuse was not possible.

Total syntheses of trikentrins and of herbindoles

CNPq

Human regulatory protein Ki-1/57 has characteristics of an intrinsically unstructured protein

The human protein Ki-1/57 was first identified through the cross reactivity of the anti-CD30 monoclonal antibody Ki-1; in Hodgkin lymphoma cells. The expression of Ki-1/57 in diverse cancer cells and its phosphorylation in peripheral blood leukocytes after mitogenic activation suggested its possible role in cell signaling. Ki-1/57 interacts with several other regulatory proteins involved in cellular signaling, transcriptional regulation and RNA metabolism, suggesting it may have pleiotropic functions. In a previous spectroscopic analysis, we observed a low content of secondary structure for Ki-1/57 constructs. Here, Circular dichroism experiments, in vitro RNA binding analysis, and limited proteolysis assays of recombinant Ki-1/57(122-413) and proteolysis assays of endogenous full length protein from human HEK293 cells suggested that Ki-1/57 has characteristics of an intrinsically unstructured protein. Small-angle X-ray scattering (SAXS) experiments were performed with the C-terminal fragment Ki-1/57(122-413). These results indicated an elongated shape and a partially unstructured conformation of the molecule in solution, confirming the characteristics of an intrinsically unstructured protein. Experimental curves together with ab initio modeling approaches revealed an extended and flexible molecule in solution. An elongated shape was also observed by analytical gel filtration. Furthermore, sedimentation velocity analysis suggested that Ki-1/57 is a highly asymmetric protein. These findings may explain the functional plasticity of Ki-1/57, as suggested by the wide array of proteins with which it is capable of interacting in yeast two-hybrid interaction assays.

Skolmisslyckande - en fråga om vårt samhälles syn på människors värde? : Normer och värderingar i svensk skolmiljö

Denna didaktiskt inriktade C-uppsats i etik tar upp elevers skolmisslyckande satt i förhållande till skolans styrdokument, lärares yrkesetik samt vårt samhälles syn på människors värde. Syftet med uppsatsen är att utifrån Iris Marion Youngs teori kring förtryck samt Harald Ofstads teori kring styrka och svaghet, ur ett etiskt/moraliskt perspektiv, söka efter svar på följande frågeställningar: Kan elever i svensk skola anses vara förtryckta enligt Youngs teori om förtryck? Kan man inom svensk skola finna tendenser till ett sådant förakt för svaghet som Ofstad diskuterar? Vilka bakomliggande strukturella förklaringar kan man utifrån dessa teorier finna till varför vissa lärare i svensk skola medvetet eller omedvetet orsakar vissa elevers känsla av att vara kränkta, misslyckade och osynliggjorda såsom uppsatsens källmaterial påvisar? Metoden består av en etisk analys av kvalitativt empiriskt källmaterial. Källmaterialet, som bygger på delar av en doktorsavhandling i filosofi författad av Carina Henriksson, analyseras med hjälp av analysverktyg skapade utifrån Youngs teori kring förtryck samt Ofstads teori kring styrka och svaghet. Slutsatsen man kan dra utifrån analyserna visar att vissa elever i svensk skola kan anses vara förtryckta samt att man inom svensk skola kan finna tendenser till förakt för svaghet. Analyserna visar även att de bakomliggande strukturella förklaringar man kan finna till detta förtryck samt förakt för svaghet handlar om traditioner som genom historiens gång blivit allmänt vedertagna och därmed normativa, trots att de motsäger de etiska principer vårt samhälle sägs bygga på, principer man kan finna i bland annat skolans värdegrund samt lärares yrkesetiska principer.

Utmaningen från andra berättelser : En studie om moraliskt omdöme, utvidgat tänkande och kritiskt reflekterande berättelser i dialogbaserad feministisk etik

The present study has a threefold aim: First, the theoretical aim is to give a contribution to refinement of the theory of dialogue based feminist ethics, concerning the understanding of judgment and narration within such an ethics.  The study also has an empirical aim, defined as to clarify what kind of knowledge, relevant to the moral judgment of an engaged outsider actor, can be received from dialogical interpretation and analysis of a limited selection of critically reflecting life stories. Third, a methodological aim is defined as to develop an approach to interpretation and analysis of reflecting life stories, which renders the storyteller visible as a reflecting moral subject, and makes the story accessible as a source of knowledge for the moral judgment of an engaged outsider actor. The thesis combines philosophical reflection and argumentation, with a narrative-hermeneutic method for interpretation of life stories, relating the two to each other in a hermeneutic process.  The theoretical reflection draws on Seyla Benhabibs theory of communicative ethics. A dialogue based model for moral justification and a likewise dialogue based model for political legitimacy are at the heart of this universalistic theory, although in combination with a conception of a narratively and hermeneutically constituted context sensitive moral judgment, based on Hannah Arendt’s concept “enlarged thought”. In the reflection, this model is related to other feminist theorizing within the tradition of dialogue based feminist ethics, as found in the works of Iris M. Young, Georgia Warnke and Shari Stone-Mediatore. The empirical study draws on three critically reflecting life stories from Israeli-Palestinian women activists for a just peace. The methodology for interpretation and analysis that is worked out combines dialogical interpretation as presented in Arthur W. Frank’s socio-narratology with a method for structural analysis derived from Shari Stone-Mediatores theory of storytelling as an expression of political resistance struggle. The results show that some stories drawing on marginalized experiences have a potential­ to stimulate further public debate through their capacity to enable a stereoscopic seeing, elucidating a tension between ideologically structured discourse and non-linguistic experience; implying that narrative-hermeneutic competence should be considered crucial for public debate.