Hepatocyte nuclear factor-4 alpha regulates the human apolipoprotein AV gene: Identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway

The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4 (HNF-4 ) as a novel regulator of human apoAV gene. Inhibition of HNF-4 expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4 directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4 consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor- coactivator-1 was capable of stimulating the HNF-4 -dependent transactivation of apoAV promoter. Furthermore, analyses in human hepatic cells demonstrated that AMP-activated protein kinase (AMPK) and the MAPK signaling pathway regulate human apoAV expression and suggested that this regulation may be mediated, at least in part, by changes in HNF-4 . Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4 gene revealed a species-distinct regulation of apoAV by HNF-4 , which resembles that of a subset of HNF-4 target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4 and underscore the role of HNF-4 in regulating triglyceride metabolism.

Is syndecan-2 a key angiogenic element?

Angiogenesis is a tightly regulated process in vertebrates that leads to the formation of new blood vessels from pre-existing vessels or by the recruitment of bone marrow-derived endothelial precursor cells[1]. During embryogenesis, after stimulation by proangiogenic factors, such as VEGF or FGF, it contributes to the maturation of the vascular plexus. In adults, it is important in some physiologic conditions, such as wound healing or the reproductive cycle in females, although most of the time it is"switched off" by endogenous inhibitors, such as endostatin or angiostatin. Furthermore, its misregulation is the cause of many pathological situations, as it contributes to tumor development[2], diabetic retinopathy[3], rheumatoid arthritis[4], psoriasis[5], but also cardiovascular disorders[6] and obesity[7]

Trace element monitoring in the ICU: quality and economic impact of a change in sampling practice.

BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant defences which are of particular importance during critical illness. Determining plasma TE levels is costly. The present quality control study aimed at assessing the economic impact of a computer reminded blood sampling versus a risk guided on-demand monitoring of plasma concentrations of selenium, copper, and zinc. METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA: to receive intravenous micronutrient supplements and/or to have a TE sampling during ICU stay. The TE samplings were triggered by computerized reminder in 2006 versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636 patients met the inclusion criteria out of 2406 consecutive admissions, representing 29.7% and 24.9% respectively of the periods' admissions. The 2009 patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p = 0.007). The number of laboratory determinations was drastically reduced in 2009, particularly during the first week, despite the higher severity of the cohort, resulting in à 55% cost reduction. CONCLUSIONS: The monitoring of TE concentrations guided by a nutritionist resulted in a reduction of the sampling frequency, and targeting on the sickest high risk patients, requiring a nutritional prescription adaptation. This control leads to cost reduction compared to an automated sampling prescription.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB)catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of glycolysis-gluconeogenesis. To gain insight into the molecular mechanism behind hormonal and nutritional regulation of PFKFB expression, we have cloned and characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1) from gilthead sea bream (Sparus aurata). Transient transfection of HepG2 cells with deleted gene promoter constructs and electrophoretic mobility shift assays allowed us to identify a sterol regulatory element (SRE) to which SRE binding protein-1a (SREBP-1a)binds and transactivates PFKFB1 gene transcription. Mutating the SRE box abolished SREBP-1a binding and transactivation. The in vivo binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed by chromatin immunoprecipitation assays. There is a great deal of evidence for a postprandial rise of PFKB1 mRNA levels in fish and rats. Consistently, starved-to-fed transition and treatment with glucose or insulin increased SREBP-1 immunodetectable levels, SREBP-1 association to PFKFB1 promoter, and PFKFB1 mRNA levels in the piscine liver. Our findings demonstrate involvement of SREBP-1a in the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert a key role mediating postprandial activation of PFKFB1 transcription.

Presenting HTML Content Using Mobile Devices

Tämä diplomityö käsittelee HTML-sivujen näyttämistä käytettävästi mobiililla päätelaitteella. Tutkimuskohteena on sivujen käytettävyyden parantaminen mobiilissa internetselaimessa. Diplomityössä esitetään havaittuja käytettävyysongelmia ja pohditaan ratkaisuja näihin selaimessa. Teoriataustaa tarkastellaan useista käytettävyyden näkökulmista, käyttäen apuna tutkimuksia ja teorioita. Tutkimuksiin ja teorioihin perustuen suunnitellaan selaimessa tapahtuvat muutokset, jotka mahdollistaisivat sivujen hyvän käytettävyyden. Tutkimusainestoa kerättiin aikaisimmista käytettävyystutkimuksista, suosituksista sekä tieteellisistä analyyseistä. Tarkastelun kohteena olivat myös nykyisten mobiilien internetselainten käyttämät ratkaisut havaittuihin käytettävyysongelmiin. Työn tuloksena esitetään mobiiliin selaimeen toteutettavat sääntöjoukot, jotka muovaisivat HTML-sivut käytettäväksi päätelaitteelle. Ratkaisuna annetaan ehdotuksia sisällön esittämistavalle ja pohditaan näissä syntyneitä ongelmia. Tulevaisuudessa kun sääntöjoukko on toteutettu selaimeen sillä suoritetaan käytettävyystestaukset.

Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB)catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of glycolysis-gluconeogenesis. To gain insight into the molecular mechanism behind hormonal and nutritional regulation of PFKFB expression, we have cloned and characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1) from gilthead sea bream (Sparus aurata). Transient transfection of HepG2 cells with deleted gene promoter constructs and electrophoretic mobility shift assays allowed us to identify a sterol regulatory element (SRE) to which SRE binding protein-1a (SREBP-1a)binds and transactivates PFKFB1 gene transcription. Mutating the SRE box abolished SREBP-1a binding and transactivation. The in vivo binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed by chromatin immunoprecipitation assays. There is a great deal of evidence for a postprandial rise of PFKB1 mRNA levels in fish and rats. Consistently, starved-to-fed transition and treatment with glucose or insulin increased SREBP-1 immunodetectable levels, SREBP-1 association to PFKFB1 promoter, and PFKFB1 mRNA levels in the piscine liver. Our findings demonstrate involvement of SREBP-1a in the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert a key role mediating postprandial activation of PFKFB1 transcription.

Software methods for HTML files protection in local / corporate networks: review and implementation

Tässä luomistyössä on esitetty tutkimus informaation suojaamisen menetelmien osalta paikallisissa ja ryhmäkuntaisissa verkoissa. Tutkimukseen kuuluu nykyaikaisten kryptagraafisten järjestelmien, Internetin/Intranetin ohjelmointikeinojen ja pääsyoikeuksien jakelumenetelmien analyysi. Tutkimusten perusteella on laadittu ohjelmiston prototyyppi HTML-tiedostojen suojaamista varten. Ohjelmiston laatimisprosessi on sisältänyt vaatimusten, järjestelmän ja suojelukomponenttien suunnittelun ja protytyypin testauksen. Ohjelmiston realisoinnin jälkeen kirjoitettiin käyttöohjeet. Ohjelmiston prototyyppi suojaa informaatiota HTML-tiedoston koko käytön aikana ja eri yrityksissä voidaan käyttää sitä pienien laajennuksien jälkeen.

Finite Element Analysis of Electrically Excited Quartz Tuning Fork Devices

Quartz Tuning Fork (QTF)-based Scanning Probe Microscopy (SPM) is an important field of research. A suitable model for the QTF is important to obtain quantitative measurements with these devices. Analytical models have the limitation of being based on the double cantilever configuration. In this paper, we present an electromechanical finite element model of the QTF electrically excited with two free prongs. The model goes beyond the state-of-the-art of numerical simulations currently found in the literature for this QTF configuration. We present the first numerical analysis of both the electrical and mechanical behavior of QTF devices. Experimental measurements obtained with 10 units of the same model of QTF validate the finite element model with a good agreement.

Effect of partial-thickness tear on loading capacities of the supraspinatus tendon: a finite element analysis.

Partial-thickness tears of the supraspinatus tendon frequently occur at its insertion on the greater tubercule of the humerus, causing pain and reduced strength and range of motion. The goal of this work was to quantify the loss of loading capacity due to tendon tears at the insertion area. A finite element model of the supraspinatus tendon was developed using in vivo magnetic resonance images data. The tendon was represented by an anisotropic hyperelastic constitutive law identified with experimental measurements. A failure criterion was proposed and calibrated with experimental data. A partial-thickness tear was gradually increased, starting from the deep articular-sided fibres. For different values of tendon tear thickness, the tendon was mechanically loaded up to failure. The numerical model predicted a loss in loading capacity of the tendon as the tear thickness progressed. Tendon failure was more likely when the tendon tear exceeded 20%. The predictions of the model were consistent with experimental studies. Partial-thickness tears below 40% tear are sufficiently stable to persist physiotherapeutic exercises. Above 60% tear surgery should be considered to restore shoulder strength.

Dose calibrator linearity test: 99mTc versus 18F radioisotopes

Objective: The present study was aimed at evaluating the viability of replacing 18F with 99mTc in dose calibrator linearity testing. Materials and Methods: The test was performed with sources of 99mTc (62 GBq) and 18F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical 99mTc and 18F sources activities were calculated and subsequently compared. Results: Mean deviations between experimental and theoretical 99mTc and 18F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the 99mTc source as measured with the equipment pre-calibrated to measure 99mTc and 18F was 3.42 (± 0.06), and for the 18F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time. Conclusion: The results of the linearity test using 99mTc were compatible with those obtained with the 18F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in 18F acquisition suggest 99mTc as the element of choice to perform dose calibrator linearity tests in centers that use 18F, without any detriment to the procedure as well as to the quality of the nuclear medicine service.

El patrimoni educatiu, un element d'una pedagogia cultural i ciutadana

El present article desenvolupa els eixos de pensament que s’estan elaborant des de diferents angles sobre el patrimoni educatiu. Una revisió sobre la importància de les aportacions de les investigacions a l’entorn del patrimoni educatiu permet assenyalar els punts d’inflexió dels museus pedagògics en l’actualitat. Entre aquests destaca la influència que els museus pedagògics, a través de les seves activitats de recerca, difusió i formació, exerceixen en la conformació d’una pedagogia cultural i ciutadana. Amb la irrupció d’una pedagogia d’encuny culturalista, els museus pedagògics recuperen els fonaments i formes de creació de discurs de la pedagogia cultural sorgida a l’inici del segle XX, tot introduint les aproximacions etnogràfiques en les arrels dels estudis i investigacions. D’altra banda, també ressalta el fet que els museus pedagògics resignifiquen la seva acció a partir de les pedagogies ètiques que atorguen un paper principal als projectes de ciutadania. Així, doncs, ambdós aspectes, cultura i ciutadania, es perfilen com els trets diferencials dels museus pedagògics actuals. A més, aquesta caracterització requereix encara d’una reflexió sobre el sentit i amplitud dels canvis introduïts en els projectes museístics.

Impact of the Femoral Head Position on Moment Arms in Total Hip Arthroplasty: A Parametric Finite Element Study.

BACKGROUND: Although the importance of accurate femoral reconstruction to achieve a good functional outcome is well documented, quantitative data on the effects of a displacement of the femoral center of rotation on moment arms are scarce. The purpose of this study was to calculate moment arms after nonanatomical femoral reconstruction. METHODS: Finite element models of 15 patients including the pelvis, the femur, and the gluteal muscles were developed. Moment arms were calculated within the native anatomy and compared to distinct displacement of the femoral center of rotation (leg lengthening of 10 mm, loss of femoral offset of 20%, anteversion ±10°, and fixed anteversion at 15°). Calculations were performed within the range of motion observed during a normal gait cycle. RESULTS: Although with all evaluated displacements of the femoral center of rotation, the abductor moment arm remained positive, some fibers initially contributing to extension became antagonists (flexors) and vice versa. A loss of 20% of femoral offset led to an average decrease of 15% of abductor moment. Femoral lengthening and changes in femoral anteversion (±10°, fixed at 15°) led to minimal changes in abductor moment arms (maximum change of 5%). Native femoral anteversion correlated with the changes in moment arms induced by the 5 variations of reconstruction. CONCLUSION: Accurate reconstruction of offset is important to maintaining abductor moment arms, while changes of femoral rotation had minimal effects. Patients with larger native femoral anteversion appear to be more susceptible to femoral head displacements.

Estereosseletividade em reações eletródicas

This review discusses the present state of the art of the stereochemistry of electrochemical reactions. The extent of asymmetric induction is progressing, but in general diastereoselectivities and enantioselectivities remain behind those from chemical synthesis. In recent years, new methodological developments have been successful. Effects that play important roles in homogeneous chemistry have been used with success. Lack of expressive enantiomeric excess (ee) could be related to the absence of tightly organized structures during the reaction of interest. The highest ee might be expected for redox reactions where conformational preference in transition state plays the important role or for the ones performed while adsorbed on the electrode, and where the chiral element is also at the surface, either adsorbed or chemically bound to the surface and interacting directly with the substrate. Electroenzymatic synthesis has a promising future.