Different concentrations of Mg++ ions affect nuclear matrix protein distribution during thermal stabilization of isolated nuclei.

The nuclear matrix, a proteinaceous network believed to be a scaffolding structure determining higher-order organization of chromatin, is usually prepared from intact nuclei by a series of extraction steps. In most cell types investigated the nuclear matrix does not spontaneously resist these treatments but must be stabilized before the application of extracting agents. Incubation of isolated nuclei at 37C or 42C in buffers containing Mg++ has been widely employed as stabilizing agent. We have previously demonstrated that heat treatment induces changes in the distribution of three nuclear scaffold proteins in nuclei prepared in the absence of Mg++ ions. We studied whether different concentrations of Mg++ (2.0-5 mM) affect the spatial distribution of nuclear matrix proteins in nuclei isolated from K562 erythroleukemia cells and stabilized by heat at either 37C or 42C. Five proteins were studied, two of which were RNA metabolism-related proteins (a 105-kD component of splicing complexes and an RNP component), one a 126-kD constituent of a class of nuclear bodies, and two were components of the inner matrix network. The localization of proteins was determined by immunofluorescent staining and confocal scanning laser microscope. Mg++ induced significant changes of antigen distribution even at the lowest concentration employed, and these modifications were enhanced in parallel with increase in the concentration of the divalent cation. The different sensitivity to heat stabilization and Mg++ of these nuclear proteins might reflect a different degree of association with the nuclear scaffold and can be closely related to their functional or structural role.

Physiopathology of the embryonic heart (with special emphasis on hypoxia and reoxygenation).

The adaptative response of the developing heart to adverse intrauterine environment such as reduced O2 delivery can result in alteration of gene expression with short- and long-term consequences including adult cardiovascular diseases. The tolerance of the developing heart of acute or chronic oxygen deprivation, its capacity to recover during reperfusion and the mechanisms involved in reoxygenation injury are still under debate. Indeed, the pattern of response of the immature myocardium to hypoxia-reoxygenation differs from that of the adult. This review deals with the structural and metabolic characteristics of the embryonic heart and the functional consequences of hypoxia and reoxygenation. The relative contribution of calcium and sodium overload, pH disturbances and oxidant stress to the hypoxia-induced cardiac dysfunction is examined, as well as various cellular signaling pathways (e.g. MAP kinases) involved in cell survival or death. In the context of the recent advances in developmental cardiology and fetal cardiac surgery, a better understanding of the physiopathology of the stressed developing heart is required.

1809 års riksgräns emellan Sverige och Ryssland Jemte special öfver trackten kring Torneå stad - 1

S.l. 1809 (?), Grav. af L.E. Personns

Recruitment of Matrix Metalloproteinase-9 (MMP-9) to the Fibroblast Cell Surface by Lysyl Hydroxylase 3 (LH3) Triggers Transforming Growth Factor-β (TGF-β) Activation and Fibroblast Differentiation.

Solid tumor growth triggers a wound healing response. Similar to wound healing, fibroblasts in the tumor stroma differentiate into myofibroblasts (also referred to as cancer-associated fibroblasts) primarily, but not exclusively, in response to transforming growth factor-β (TGF-β). Myofibroblasts in turn enhance tumor progression by remodeling the stroma. Among proteases implicated in stroma remodeling, matrix metalloproteinases (MMPs), including MMP-9, play a prominent role. Recent evidence indicates that MMP-9 recruitment to the tumor cell surface enhances tumor growth and invasion. In the present work, we addressed the potential relevance of MMP-9 recruitment to and activity at the surface of fibroblasts. We show that recruitment of MMP-9 to the fibroblast cell surface occurs through its fibronectin-like (FN) domain and that the molecule responsible for the recruitment is lysyl hydroxylase 3 (LH3). Functional assays suggest that both pro- and active MMP-9 trigger α-smooth muscle actin expression in cultured fibroblasts, reflecting myofibroblast differentiation, possibly as a result of TGF-β activation. Moreover, the recombinant FN domain inhibited both MMP-9-induced TGF-β activation and α-smooth muscle actin expression by displacing MMP-9 from the fibroblast cell surface. Together our results uncover LH3 as a new docking receptor of MMP-9 on the fibroblast cell surface and demonstrate that the MMP-9 FN domain is essential for the interaction. They also show that the recombinant FN domain inhibits MMP-9-induced TGF-β activation and fibroblast differentiation, providing a potentially attractive therapeutic reagent toward attenuating tumor progression where MMP-9 activity is strongly implicated.

Development of Special Pumps Repair Process

Tässä diplomityössä käsitellään erikoispumppujen korjausprosessia teollisuuspumppujen korjauksiin erikoistuneessa konepajassa. Työn pääasiallinen tarkoitus on tuotantoprosessin kehittäminen ja tuotantovaiheiden esitteleminen. Tavoitteen taustalla on pyrkimys entisestään parantaa palvelukykyä ja asiakastyytyväisyyttä.Kolme eri keinoa päätavoitteen saavuttamiseksi ovat tuotannon suunnittelun ja ohjauksen kehittäminen, työssä käsiteltyjen pumpputyyppien korjausprosessien läpäisyaikojen lyhentäminen sekä korjausvaiheiden määrittely ja esittely vaihe vaiheelta. Työssä käsiteltyjä erikoispumpputyyppejä ovat imupumput, monijaksopumput sekä pysty/potkuripumput.Tuotannonsuunnittelun ja -ohjauksen kehittämiseksi sekä läpäisyaikojen lyhentämiseksi työssä etsittiin vaihtoehtoisia toimintatapoja. Kolmas tavoite, eli korjausvaiheiden määrittely, toteutettiin esittelemällä korjausprosessin vaiheet käsitellyillä pumpputyypeillä.Tuloksena saatiin keinoja tuotannon suunnittelun ja hallinnan kehittämiseksi. Useimmat keinot koskevat toimintatapojen selkiyttämistä. Myös keinoja läpäisyaikojen lyhentämiseksi löydettiin. Tietyllä imupumpputyypillä ja -koolla läpäisyajan lyheneminen oli 25 % ja osalla monijaksopumpuista jopa 75 %. Tulokset saavutetaan varastoimalla tiettyjä komponentteja, joilla on pitkä valmistus- tai korjausaika. Pysty/potkuripumppujen korjauksen läpäisyaikaa ei saatu lyhennettyä työn rajausten puitteissa Näiden tulosten lisäksi korjausprosessin toimintatavat määriteltiin.

The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (-)-Epicatechin metabolites in healthy humans subjects

The effect of different food matrices on the metabolism and excretion of polyphenols is uncertain. The objective of the study was to evaluate the possible effect of milk on the excretion of (2)-epicatechin metabolites from cocoa powder after its ingestion with and without milk. Twenty-one volunteers received the following three test meals each in a randomised cross-over design with a 1-week interval between meals: (1) 250 ml whole milk as a control; (2) 40 g cocoa powder dissolved in 250 ml whole milk (CC-M); (3) 40 g cocoa powder dissolved in 250 ml water (CC-W). Urine was collected before consumption and during the 0-6, 6-12 and 12-24 h periods after consumption. (2)-Epicatechin metabolite excretion was measured using liquid chromatography-MS. One (2)-epicatechin glucuronide and three (2)-epicatechin sulfates were detected in urine excreted after the intake of the two cocoa beverages (CC-M and CC-W). The results show that milk does not significantly affect the total amount of metabolites excreted in urine. However, differences in metabolite excretion profiles were observed; there were changes in the glucuronide and sulfate excretion rates, and the sulfation position between the period of excretion and the matrix. The matrix in which polyphenols are consumed can affect their metabolism and excretion, and this may affect their biological activity. Thus, more studies are needed to evaluate the effect of these different metabolite profiles on the body.

Market Potential and Demand Drivers for a Special Laminating Paper: Implementation of Market Research

Tutkimuksen tavoitteena oli selvittää raaka-aineena käytettävän paloa hidastavan laminaattipaperin markkinapotentiaali sekä kysyntä Euroopassa. Näiden kehitystä arvioitiin analysoimalla kysyntään vaikuttavia tekijöitä. Tutkimusmetodologiassa yhdistyivät useat lähestymistavat, pääasiassa käytettiin kuvailevaa ja ennustavaa tutkimusotetta. Tutkimus perustui sekä primaari että sekundaaritietoon. Primaaritietoa hankittiin tuotteen käyttäjiltä, myyntiedustajilta sekä haastattelemalla tuottajayrityksen henkilökuntaa. Sekundaaritietoa kerättiin myös, mutta tutkimuksen tavoitteisiin liittyviä lähteitä ei ollut runsaasti saatavilla. Tästä syystä primaaritiedolla oli tutkimuksessa hieman tärkeämpi rooli kuin sekundaaritiedolla, mikä on yleistä teollisessa markkinatutkimuksessa. Tuotteen tulevaisuuden näkymät vaikuttavat melko hyviltä. Teoreettinen markkinapotentiaali on suuri verrattuna nykyiseen myyntimäärään, myyntimäärän kasvattaminen vaatii kuitenkin tiettyjä toimenpiteitä. Tulevaisuudessa huomiota tulisi kiinnittää tuotekuvaan, hinnoitteluun ja laadun kokonaisvaltaiseen maksimointiin. Tutkimuksessa havaittiin suuntauksia kysynnän kasvusta tulevien parin vuoden aikana. Myös teoreettinen markkinapotentiaali voisi kasvaa, koska paloa hidastavien laminaattien kysyntä vaikuttaa kasvavan Euroopassa erityisesti rakennusalalla.

Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome.

Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome (MIM 600373) was first described and named by Shehib et al, in 1991 in a single patient. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. This distinctive constellation of anatomical findings should allow easy recognition but despite this only four apparently sporadic patients have been reported in the last 20 years indicating that the full phenotype is indeed very rare with perhaps milder or a typical presentations that are allelic but without sufficient phenotypic resemblance to permit clinical diagnosis. We performed exome sequencing in three patients (an isolated case and a brother and sister sib pair) with classical features of CODAS. Sanger sequencing was used to confirm results as well as for mutation discovery in a further four unrelated patients ascertained via their skeletal features. Compound heterozygous or homozygous mutations in LONP1 were found in all (8 separate mutations; 6 missense, 1 nonsense, 1 small in-frame deletion) thus establishing the genetic basis of CODAS and the pattern of inheritance (autosomal recessive). LONP1 encodes an enzyme of bacterial ancestry that participates in protein turnover within the mitochondrial matrix. The mutations cluster at the ATP-binding and proteolytic domains of the enzyme. Biallelic inheritance and clustering of mutations confirm dysfunction of LONP1 activity as the molecular basis of CODAS but the pathogenesis remains to be explored.

1D.03: Inactive matrix GLA protein is associated with renal resistive index in a population-based study

OBJECTIVE: Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD: We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS: We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P < 0.001). CONCLUSIONS: RRI is independently and positively associated with high levels of dp-ucMGP after adjustment for pulse pressure and common CV risk factors. Further studies are needed to determine if vitamin K supplementation can have a positive effect on renal vascular stiffness and kidney function.

Matrix Analytic Analysis of Delays in Communication Systems

Tässä päättötyössä annetaan kuvaus kehitetystä sovelluksesta Quasi Birth Death processien ratkaisuun. Tämä ohjelma on tähän mennessä ainutlaatuinen ja sen avulla voi ratkaista sarjan tehtäviä ja sitä tarvitaan kommunikaatio systeemien analyysiin. Mainittuun sovellukseen on annettu kuvaus ja määritelmä. Lyhyt kuvaus toisesta sovelluksesta Quasi Birth Death prosessien tehtävien ratkaisuun on myös annettu