3,778 research outputs found
Eicosapentaenoic acid and 3,10 dithia stearic acid inhibit the desaturation of trans-vaccenic acid into cis-9, trans-11-conjugated linoleic acid through different pathways in Caco-2 and T84 cells.
No full textStearoyl-CoA desaturase (SCD) is a key enzyme that determines the composition and metabolic fate of ingested fatty acids, in particular the conversion of trans-vaccenic acid (TVA) to conjugated linoleic acid (CLA). The present study addressed the hypothesis that intestinal TVA absorption and biotransformation into CLA can be modulated by EPA and 3,10-dithia stearic acid (DSA) via altered SCD mRNA levels and desaturation indices (cis-9, trans-11-CLA:TVA and oleic acid:stearic acid ratios) in Caco-2 and T84 cells, two well-established in vitro models of the human intestinal epithelium. The study determined the effect of acute (3 h with 0.3 mm-EPA or 0.3 mm-DSA) and acute-on-chronic (1 week with 0.03 mm-EPA or -DSA, followed by respectively, 0.3 mm-EPA or -DSA for 3 h) treatments. In both cell lines, acute EPA treatment did not alter SCD desaturation indices, whereas the acute-on-chronic treatment affected these surrogate markers of SCD activity. This was associated with reduced sterol regulatory-element binding protein-1c and SCD mRNA levels. In contrast, acute and acute-on-chronic DSA treatments significantly reduced SCD desaturation indices without affecting SCD mRNA levels in Caco-2 cells. The present study on intestinal cells shows that the conversion rate of TVA to c9, t11-CLA is affected by other fatty acids present in the diet such as EPA, confirming previous observations in hepatic and mammary cell models
An assessment of the impact of possible CAP reform scenarios on Romanian agriculture
No full textUsing a simplified model, with key-variable the prices of two different possible scenarios of CAP reform after 2013 (moderate and radical), this paper present a comparison between the price effects of implementation of each reform scenario at 2015 horizon on Romanian agriculture. This short analysis shows that, under the presented hypotheses, the net welfare effect, due to the price changes, for the selected products, is positive in both reform scenarios, yet greater in the case of the radical reform. Integrated in the large context of Romanian development, it seems that the influence of CAP reform upon agriculture and rural areas will be most likely a gradual one: an interpenetration between the two scenarios is foreseeable, starting with the moderate reform that will dominate the period around 2013, the reform measures acquiring a more radical character afterwards.CAP reform, Romania, welfare effects, Agricultural and Food Policy,
Model for role of Mob binding and HM phosphorylation in NDR/LATS kinase activation.
No full text<p>Mob supports the NDR/LATS kinase N-terminal extension in a conformation that creates a binding slot for both HM-T and HM-P. (A) HM-T remains associated with the N-linker region in a manner that does not promote an ordered conformation of the αC helix. (B) HM-P promotes reorganization of αMob, compressing the HM binding slot and holding aromatic side chains of the HM in a configuration that favors ordering of αC.</p
Inhibitors of Helicobacter pylori protease HtrA found by "virtual ligand" screening combat bacterial invasion of epithelia
No full textBackground: The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings: We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance: This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection
Prevalence and clinical picture of celiac disease in Turner syndrome
No full textPrevalence and clinical picture of celiac disease in Turner syndrome.
Bonamico M1, Pasquino AM, Mariani P, Danesi HM, Culasso F, Mazzanti L, Petri A, Bona G; Italian Society Of Pediatric Gastroenterology Hepatology (SIGEP); Italian Study Group for Turner Syndrom (ISGTS).
Author information 1Department of Pediatrics, University of Rome La Sapienza, 00161 Roma, Italy.
Abstract
A multicenter study of Turner syndrome (TS) patients was carried out to estimate the prevalence of celiac disease (CD) and to detect clinical characteristics and laboratory data of affected patients. Three hundred eighty-nine girls with TS were screened by IgA antigliadin antibodies and/or antiendomysial antibodies. Intestinal biopsy was offered to positive cases. CD was diagnosed in 25 patients. In celiac subjects, anemia, anorexia, and delayed growth (with respect to Italian TS curves) were frequently present; whereas distended abdomen, chronic diarrhea, constipation, and vomiting occurred more rarely. In addition, low serum iron levels, hemoglobinemia, and high values of aminotransferases were observed. Ten patients showed classic CD, 8 showed atypical symptoms, and 7 showed a silent CD. In 11 symptomatic patients, the diagnosis of CD was made at the onset of symptoms, whereas 7 of them showed a median delay of 79 months in diagnosis. Other autoimmune disorders were observed in 40% of the patients. Our study confirms the high prevalence (6.4%) of CD in a large series of TS patients. Moreover, the subclinical picture in 60% of the cases, the diagnostic delay, and the incidence of other autoimmune disorders suggest that routine screening of CD in TS is indicated
Documenting Impacts of Hydro-Meteorological Events Using Earth Observation
No full textThe ambition of H2020 OPERANDUM project is to develop and document Nature Based Solutions (NBS) to mitigate risks associated with hydro-meteorological (HM) hazards. NBS mitigate risks by reducing the vulnerability of a particular system. The aim of this work is to demonstrate the use of multisource remote sensing data in documenting the impact of extreme HM events to advance knowledge on vulnerability and exposure. In particular the focus is to document past impacts due to extreme events selected from a characterization of recent (3 0 years) HM events in 11 Open Air Laboratories (OALs) where co-design, co-development and deployment of NBS are taking place. The impacts were documented by applying a wide spectrum of satellite image data and other, close - range, remote sensing techniques. A better understanding of the consequences due to extreme HM events in a particular area (OALs) is essential to identify elements at risk and expected to provide a reference to evaluate the reduction of vulnerability and mitigation of risks past the completion of NBS.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Optical and Laser Remote SensingGeo-engineerin
Molecular dynamics simulation indicates phosphorylation-induced rearrangement of the NDR/LATS kinase HM-binding slot to favor enzyme activation.
No full text<p>(A) Comparison of the Cbk1 HM with the HM of PKB. The panel shows the Cbk1–Mob2 complex superimposed with PKB, where the αC helix and the HM of the superimposed PKB are shown in yellow (PDB ID: 1O6K). Side chains of important HM residues are shown with sticks. Superimposition of PKB and Cbk1–Mob2 reveals that the main chains of the HM motifs are >7 Å apart. The Cbk1 HM motif is shifted upwards to bind to the upper part of the HM-binding slot, while the PKB HM binds close to the N-terminal PKB kinase lobe. (B) Cbk1–Mob2 complexes in which T743 in the C-terminal HM is either dephosphorylated (HM-T) or phosphorylated (HM-P) were subjected to 125-ns MD simulations. Here we represent indicated regions of Cbk1 as centers of mass of the following: HM, amino acids 742–749; N-linker, amino acids 341–346; αC, amino acids 393–406; αMob, amino acids 297–317. We started distances of both HM forms to the N-linker region, αC, and αMob at [8.7 Å; 18.0 Å; 14.9 Å], corresponding to the conformational state captured in the Cbk1–Mob2 complex crystal structure, and recalculated the distances between HM forms, N-linker, αC, and αMob after each simulation step. (C) Three-dimensional scatter plots show 100 ns of the simulations, with each dot indicating N-linker–HM, αC–HM, and αMob–HM distances (<i>x-</i>, <i>y-</i>, and <i>z</i>-axes) for each nanosecond. For clarity, dots are colored from blue to red according to their αMob–HM distances (<i>z</i>-axis). The complex with HM-P exhibits shorter distances and smaller changes in position, indicating that T743 phosphorylation compresses the HM-binding slot and constrains the HM region association. This occurs only in Cbk1 bound to Mob coactivator (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002146#pbio.1002146.s011" target="_blank">S5 Fig</a>). (D) HM phosphorylation promotes αMob bending and compresses the HM binding slot. Secondary structure analysis of αMob illustrates that this region remains helical (blue) when HM-T is bound, but acquires a short turn (yellow) when HM-P is bound. (E) An enlarged view of the final MD-simulated Cbk1(HM-P)–Mob2 complex indicates the HM-P’s interactions that bend αMob, as well as van der Waals contacts with αC. (F) Ionic interactions suggested by the MD model (E314/R746 and R307/pT743) (left) were tested by charge swapping and analysis of cell separation. Single mutants (grey) displayed larger group sizes, indicating defective RAM network function, but were partially recovered when both charged sites were swapped (red). Data for (C) and (F) can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002146#pbio.1002146.s001" target="_blank">S1 Data</a>.</p
The progress and outcomes of black and minority ethnic (BME) nurses through the Nursing and Midwifery Council's "Fitness to Practise" process: Final report
No full textBACKGROUND
This is the first investigation of the relationship between ethnicity and regulation of the nursing profession conducted internationally. The study was commissioned by the Nursing and Midwifery Council which is the regulator of the professions in the UK.
AIMS OF THE STUDY
“To establish whether the progress and outcomes of Black and minority ethnic (BME) nurses in relation to fitness to practice, from the point of referral to the point of case closure, is different from that of White nurses and midwives (N&M); and whether we can from the data account for any differences identified” (Call for research, NMC 2015). The study was designed to investigate whether BME N&M nurses are more likely to be referred and whether they were more likely to progress through the stages of the Fitness to Practise (FtP) process (screening, investigation or adjudication) and whether they were more likely to receive a severe penalty at the end of the process.
DATA
The NMC made available a copy of the register which had socio-demographic information on 681,258 nurses and midwives between April 2012 and December 2014 as well as data on referrals from April 2012 to December 2014 which totalled 5,851. Over that period the total number of cases that went to adjudication was 946.
VARIABLES
The main independent variable is ethnicity which we divided into Black, Asian, White, Other and Unknown. The latter category accounted for 40% of all referrals. The outcomes studied were rates of referral, the imposition of interim orders (where the referred individual is not allowed to work, progression through screening, investigation, adjudication and final outcome, which was dichotomised into “can work” or “cannot work”. The regression models also controlled for: age, gender, source of referral (9 categories), region of qualification (Africa, Asia, Europe, Other, UK), country of referral (4 counties of the UK) and whether or not the individual referred had a representative, such as a Union.
METHODS OF ANALYSIS
Descriptive statistics, cross-tabulation analysis, logistic regression and ordinal logistic regression
FINDINGS
Descriptive statistics showed that BME nurses are more likely to be referred than white nurses and to progress through the FtP process. Having trained in Africa is also a risk factor for referral. Older N&M and males are more likely to be referred. Most referrals come from employers but members of the public are also an important source of referral. Inferential statistics show that relative to Whites, being Asian, Black or of Unknown ethnicity is associated with progressing through FtP process. However, when “source of referral” is entered into the regression model only the “Unknown ethnicity” category remains significantly more likely to progress than White N&M. Males are more likely to progress through the FtP process but age, though positive, is not significant. There were few significant differences among the countries of the UK. The imposition of interim orders did not vary by ethnicity. The presence of a representative seems to reflect the stage of the FtP process rather than being a factor that contributes to the outcome. Finally, at adjudication, being Asian or Black is associated with a less severe penalty than White. Only those of Unknown ethnicity are more likely than Whites to get a severe penalty. These results are not altered by controlling for the source of referral.
STRENGTHS AND WEAKNESSES OF THE STUDY
The strengths include: the fact that this is the first study of its kind, the datasets analysed are large and the statistics are appropriate. Weakness include the fact that in 40% cases the ethnicity of the referred individual is not known. Some of the registered N&M may not be working which means that their risk of being referred to the NMC is low which could be a threat to the comparison of different ethnic groups. The administrative data which we analysed did not provide information about the specialty (e.g. mental health, maternity), job setting (care home, acute hospital) or level of seniority (staff nurse or Director of Nursing of the individuals referred were not amenable to analysis.
RECOMMENDATIONS
The analysis reported here could be enhanced in the future if the information on ethnicity, the setting in which the referred individual is working and their grade is made available. Some jobs may simply carry a higher risk of referral to the NMC and BME nurses may disproportionately occupy those positions. The main finding, which is that the relationship between ethnicity and FtP is mediated by referral by the employer, directs our attention to the need for further research to understand how the working environment leads to an over-representation of BME nurses in the FtP process. Within the NMC, further research needs to be conducted to understand why White nurses are more likely to be given a severe penalty at adjudication even though they are underrepresented in referrals and less likely to progress through the process. With the introduction of the NMC code and revalidation, the collection of data by the NMC and the FtP process will undoubtedly change. At the same time, the NHS has introduced policies to directly affect the working environment of BME nurses and midwives. This means that this study should be repeated to take account of these changes in the wider environment
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