Transthyretin familial amyloid polyneuropathy impact on health-related quality of life

info:eu-repo/semantics/publishedVersio

An unmixing algorithm for remotely sensed soil moisture

We present an unmixing method, based on genetic algorithm-soil-vegetation-atmosphere-transfer modeling to extract subgrid information of soil and vegetation from remotely sensed soil moisture (downscaled; e.g., soil hydraulic properties, area fractions of soil-vegetation combinations, and unmixed soil moisture time series) that most land surface models use. The unmixing method was evaluated using numerical experiments comprising mixed pixels with simple and complex soil-vegetation combinations, in idealized case studies (with or without uncertainty) and under actual field conditions (Walnut Creek (WC11) field, Soil Moisture Experiment 2005, Iowa). Additional validation experiments were conducted at an airborne-remote sensing footprint (Little Washita (LW21) site, Southern Great Plains 1997 hydrology campaign, Oklahoma) using Electronically Scanning Thin Array Radiometer (ESTAR). Results of the idealized experiments suggest that the unmixing method can extract optimal or near-optimal solutions to the inverse problem under different hydrologic and climatic conditions. Errors in soil moisture data and initial and boundary conditions can compound uncertainty in the solution. The solutions generated under actual field conditions (WC11 field) were able to match soil moisture observations. Analysis showed that typical soil moisture retention curves of cataloged dominant soils in WC11 field did not match well with the measurements, but those derived from actual field-scale soil moisture inversion matched better. The unmixing method performed well in replicating soil hydraulic behavior at the ESTAR footprint. Unlike in WC11 field, the typical soil moisture retention curves of cataloged soils in LW21 field matched better with the measurements. We envisaged that the unmixing method can provide quick and easy way of extracting subgrid soil moisture variability and soil-vegetation information in a pixel

The Tyrosine Kinase BceF and the Phosphotyrosine Phosphatase BceD of Burkholderia contaminans Are Required for Efficient Invasion and Epithelial Disruption of a Cystic Fibrosis Lung Epithelial Cell Line

Bacterial tyrosine kinases and their cognate protein tyrosine phosphatases are best known for regulating the biosynthesis of polysaccharides. Moreover, their roles in the stress response, DNA metabolism, cell division, and virulence have also been documented. The aim of this study was to investigate the pathogenicity and potential mechanisms of virulence dependent on the tyrosine kinase BceF and phosphotyrosine phosphatase BceD of the cystic fibrosis opportunistic pathogen Burkholderia contaminans IST408. The insertion mutants bceD::Tp and bceF::Tp showed similar attenuation of adhesion and invasion of the cystic fibrosis lung epithelial cell line CFBE41o- compared to the parental strain B. contaminans IST408. In the absence of bceD or bceF genes, B. contaminans also showed a reduction in the ability to translocate across polarized epithelial cell monolayers, demonstrated by a higher transepithelial electrical resistance, reduced flux of fluorescein isothiocyanate-labeled bovine serum albumin, and higher levels of tight junction proteins ZO-1, occludin, and claudin-1 present in monolayers exposed to these bacterial mutants. Furthermore, bceD::Tp and bceF::Tp mutants induced lower levels of interleukin-6 (IL-6) and IL-8 release than the parental strain. In conclusion, although the mechanisms of pathogenicity dependent on BceD and BceF are not understood, these proteins contribute to the virulence of Burkholderia by enhancement of cell attachment and invasion, disruption of epithelial integrity, and modulation of the proinflammatory response

Generation of a library of carbohydrate-active enzymes for plant biomass deconstruction

Áreas de pesquisa: Biochemistry & Molecular Biology ; ChemistryIn nature, the deconstruction of plant carbohydrates is carried out by carbohydrate-active enzymes (CAZymes). A high-throughput (HTP) strategy was used to isolate and clone 1476 genes obtained from a diverse library of recombinant CAZymes covering a variety of sequence-based families, enzyme classes, and source organisms. All genes were successfully isolated by either PCR (61%) or gene synthesis (GS) (39%) and were subsequently cloned into Escherichia coli expression vectors. Most proteins (79%) were obtained at a good yield during recombinant expression. A significantly lower number (p < 0.01) of proteins from eukaryotic (57.7%) and archaeal (53.3%) origin were soluble compared to bacteria (79.7%). Genes obtained by GS gave a significantly lower number (p = 0.04) of soluble proteins while the green fluorescent protein tag improved protein solubility (p = 0.05). Finally, a relationship between the amino acid composition and protein solubility was observed. Thus, a lower percentage of non-polar and higher percentage of negatively charged amino acids in a protein may be a good predictor for higher protein solubility in E. coli. The HTP approach presented here is a powerful tool for producing recombinant CAZymes that can be used for future studies of plant cell wall degradation. Successful production and expression of soluble recombinant proteins at a high rate opens new possibilities for the high-throughput production of targets from limitless sourcesinfo:eu-repo/semantics/publishedVersio

FAD-Linked Autofluorescence and Chemically-Evoked Zinc Changes at Hippocampal Mossy Fiber-CA3 Synapses

Glutamatergic vesicles in hippocampal mossy fiber presynaptic boutons release zinc, which plays a modulatory role in synaptic activity and LTP. In this work, a fluorescence microscopy technique and the fluorescent probe for cytosolic zinc, Newport Green (NG), were applied, in a combined study of autofluorescence and zinc changes at the hippocampal mossy fiber-CA3 synaptic system. In particular, the dynamics of flavoprotein (FAD) autofluorescence signals, was compared to that of postsynaptic zinc signals, elicited both by high K+ (20 mM) and by tetraethylammonium (TEA, 25 mM). The real zinc signals were obtained subtracting autofluorescence values, from corresponding total NG-fluorescence data. Both autofluorescence and zinc-related fluorescence were raised by high K+. In contrast, the same signals were reduced during TEA exposure. It is suggested that the initial outburst of TEA-evoked zinc release might activate ATP-sensitive K+ (KATP) channels, as part of a safeguard mechanism against excessive glutamatergic action. This would cause sustained inhibition of zinc signals and a more reduced mitochondrial state. In favor of the “KATP channel hypothesis”, the KATP channel blocker tolbutamide (250 μM) nearly suppressed the TEA-evoked fluorescence changes. It is concluded that recording autofluorescence from brain slices is essential for the accurate assessment of zinc signals and actions

TOIMINNANOHJAUSJÄRJESTELMÄN KÄYTTÖÖNOTON VAIKUTUS

Tässä tutkielmassa tutkitaan kuinka toiminnanohjausjärjestelmän käyttöönotto on vaikuttanut yrityksen tulokseen ja suorituskykyyn suomalaisissa yrityksissä 1999-2015. Tavoitteena on testata empiirisesti aiheuttaako toiminnanohjausjärjestelmän käyttöönotto merkittäviä säästöjä, yrityk-sen toiminnan tehokkuuden parannuksia ja muutoksia yrityksen kannattavuudessa. Toiminnanohjaus- eli ERP-järjestelmät integroivat yrityksen eri toimintoja esimerkiksi logistiikkaa, tuotantoa, kirjanpitoa, varastointia ja laskutusta yhteen järjestelmään ja näin ollen tehostavat yrityksen toimintaa useiden eri järjestelmien käytön sijaan. Onkin tärkeää selvittää kuinka toiminnanohjausjärjestelmien käyttöönotto on vaikuttanut yritysten kannattavuuteen ja voidaanko investointi nähdä tuottavana. Aikaisempien tutkimusten perusteella tulokset ovat ristiriitaisia; tutkimukset osoittavat, että vaikka ERP- järjestelmien käyttöönotto tutkitusti vaikuttaa ei-rahamääräisiin mittareihin, vaikutusta rahamääräisiin mittareihin ei aina pystytä todistamaan. Yritysten kannalta mielenkiintoista onkin ovatko kalliit ERP-järjestelmät, sekä niiden implementointiprosessit todella kannattavia investointeja. Tutkimuksen empiirisessä osiossa selvitettiin toiminnanohjausjärjestelmien käyttöönoton vaiku-tuksia suorituskykyyn suomalaisissa yhtiöissä, jotka ovat implementoineet toiminnanohjausjärjestelmän vuosina 1999-2015. Aineistona on käytetty julkisuudessa ilmoitettuja järjestelmähank-keita sekä tilinpäätöstietoja implementointiprosessin jälkeisiltä sekä edeltäviltä vuosilta. Suorituskyvyn muutosta on seurattu vertailemalla suorituskyvyn ja kannattavuuden muutosta implementoinnin jälkeen. Tutkimus on suoritettu määrällisenä tutkimuksena ja tilastollisina menetelminä on käytetty toistomittausten varianssianalyysiä sekä t-testiä parivertailulle. Tutkimuksessa havaittiin, että näyttäisi siltä, ettei toiminnanohjausjärjestelmien käyttöönotolla ei ole ollut vaikutusta kohdeyhtiöiden rahamääräiseen suorituskykyyn.fi=Opinnäytetyö kokotekstinä PDF-muodossa.|en=Thesis fulltext in PDF format.|sv=Lärdomsprov tillgängligt som fulltext i PDF-format

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry