Ενδομήτρια μετάδοση του ιού των ανθρωπίνων θηλωμάτων – Μια συστηματική ανασκόπηση της βιβλιογραφίας

Σκοπός: Σκοπός της παρούσας μελέτης είναι να γίνει μια συστηματική ανασκόπηση στη διεθνή βιβλιογραφία σχετικά με την ενδομήτρια μετάδοση του ιού των ανθρωπίνων θηλωμάτων και να υπολογιστεί το ποσοστό ενδομήτριας μετάδοσης του ιού σε HPV θετικές μητέρες. Δευτερευόντως θα υπολογίσουμε το σχετικό κίνδυνο ενδομήτριας μετάδοσης του ιού μεταξύ καισαρικής τομής και φυσιολογικού τοκετού Μέθοδοι: Η συστηματική ανασκόπηση έγινε με βάση τις οδηγίες PRISMA σε PubMed και Scopus. Η αξιολόγηση και η επιλογή των μελετών έγινε από δύο ερευνητές και τα δεδομένα από κάθε μελέτη που επελέγη καταγράφηκαν σε ειδικές φόρμες. Υπολογίστηκε η συχνότητα της ενδομήτριας μετάδοσης σε κάθε μελέτη και ακολούθησε μεταανάλυση και υπολογισμός της συνολικής συχνότητας. Επίσης υπολογίστηκε και ο σχετικός κίνδυνος ενδομήτριας μετάδοσης μεταξύ καισαρικής και φυσιολογικού τοκετού. Αποτελέσματα: Από 434 μελέτες επελέγησαν τελικά 9 που περιλαμβάνουν 421 HPV θετικές μητέρες και τα νεογνά τους. Από τη μεταανάλυση των δεδομένων προέκυψε μια συνολική πιθανότητα ενδομήτριας μετάδοσης του HPV 4,936% (95%CI 1,651 – 9,849) μεγάλη ετερογένεια μεταξύ των μελετών (I2 = 72,21%) ενώ ο συνολικός σχετικός κίνδυνος ενδομήτριας κάθετης μετάδοσης του ιού των ανθρώπινων θηλωμάτων μεταξύ νεογνών που γεννήθηκαν με καισαρική τομή, και νεογνών που γεννήθηκαν φυσιολογικά από θετικές στον ιό μητέρες υπολογίστηκε 0,912,χωρίς στατιστική σημασία (95%CI 0.226-3.674) και με μικρή ετερογένεια μεταξύ των μελετών (I2 24.48%).Objectives: To evaluate the percentage of antenatal vertical HPV transmission among HPV positive mothers and the relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women. Methods: This systematic review was made according to PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated. Results: 9 studies including 421 HPV positive mothers and their offspring were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4,936% (95%CI 1,651 – 9,849) with high heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0,912, with no statistical significance (95%CI 0.226-3.674) and homogeneity between the studies (I2 24.48%)

Distinct ensembles in the noradrenergic locus coeruleus are associated with diverse cortical states

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical "activated" cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased highfrequency power as well as other states including decreased high-frequency power. Thus-in contrast to the stereotypical activated brain state evoked by en masse LC stimulation-spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.Peer reviewe

Ontbindend en bindend besturen van de omgeving:Juridisering in de praktijk van omgevingsbesluitvorming

Besluitvorming over de fysieke leefomgeving vindt plaats in een sterk gejuridiseerde context. Het aantal bezwaren en beroepen neemt toe en de Omgevingswet maakt hieraan geen einde. Juridisering leidt nogal eens tot ontbindend bestuur: belanghebbenden keren zich verder van elkaar af en zijn minder bereid en in staat om met elkaar tot oplossingen te komen. Ontbindend en bindend besturen van de omgeving verkent hoe juridisering werkt en de mechanismen die leiden tot binding en ontbinding. Ook beschrijft het boek naast juridiseren twee andere actierepertoires: participeren en politiseren. Met de analyse van de werking en bijwerkingen van alle drie de repertoires kunnen bestuurders, burgers, bedrijven en actie groepen hun handelen afstemmen op de situatie. Een goed gekozen mix van juridiseren, participeren en politiseren versterkt de legitimiteit en de effectiviteit van de besluiten, maakt bindend besturen van de fysieke omgeving mogelijk en bespaart alle partijen een hoop ellende. Dit boek is een vrucht van het kennisprogramma Bindend besturen in Brabant, een initiatief van de provincie Noord-Brabant, Tilburg University en Pontifa

Algoritmische rechtstoepassing in de democratische rechtsstaat

FdR – Publicaties niet-programma gebonde

Recht door de windtunnel

FDR Het institutionele en rechtsstatelijke kader van de rechtspleging - ou

The role of tRNA and ribosome competition in coupling the expression of different mRNAs in Saccharomyces cerevisiae

Protein synthesis translates information from messenger RNAs into functional proteomes. Because of the finite nature of the resources required by the translational machinery, both the overall protein synthesis activity of a cell and activity on individual mRNAs are controlled by the allocation of limiting resources. Upon introduction of heterologous sequences into an organism—for example for the purposes of bioprocessing or synthetic biology—limiting resources may also become overstretched, thus negatively affecting both endogenous and heterologous gene expression. In this study, we present a mean-field model of translation in Saccharomyces cerevisiae for the investigation of two particular translational resources, namely ribosomes and aminoacylated tRNAs. We firstly use comparisons of experiments with heterologous sequences and simulations of the same conditions to calibrate our model, and then analyse the behaviour of the translational system in yeast upon introduction of different types of heterologous sequences. Our main findings are that: competition for ribosomes, rather than tRNAs, limits global translation in this organism; that tRNA aminoacylation levels exert, at most, weak control over translational activity; and that decoding speeds and codon adaptation exert strong control over local (mRNA specific) translation rates

Translation elongation can control translation initiation on eukaryotic mRNAs

Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon usage to protein expression levels. Here, we demonstrate a novel translational control mechanism that responds to the speed of ribosome movement immediately after the start codon. High initiation rates are only possible if start codons are liberated sufficiently fast, thus accounting for the observation that fast codons are overrepresented in highly expressed proteins. In contrast, slow codons lead to slow liberation of the start codon by initiating ribosomes, thereby interfering with efficient translation initiation. Codon usage thus evolved as a means to optimise translation on individual mRNAs, as well as global optimisation of ribosome availability

Stochastic theory of protein synthesis and polysome: ribosome profile on a single mRNA transcript

The process of polymerizing a protein by a ribosome, using a messenger RNA (mRNA) as the corresponding template, is called {\it translation}. Ribosome may be regarded as a molecular motor for which the mRNA template serves also as the track. Often several ribosomes may translate the same (mRNA) simultaneously. The ribosomes bound simultaneously to a single mRNA transcript are the members of a polyribosome (or, simply, {\it polysome}). Experimentally measured {\it polysome profile} gives the distribution of polysome {\it sizes}. Recently a breakthrough in determining the instantaneous {\it positions} of the ribosomes on a given mRNA track has been achieved and the technique is called {\it ribosome profiling} \cite{ingolia10,guo10}. Motivated by the success of these techniques, we have studied the spatio-temporal organization of ribosomes by extending a theoretical model that we have reported elsewhere \cite{sharma11}. This extended version of our model incorporates not only (i) mechano-chemical cycle of individual ribomes, and (ii) their steric interactions, but also (iii) the effects of (a) kinetic proofreading, (b) translational infidelity, (c) ribosome recycling, and (d) sequence inhomogeneities. The theoretical framework developed here will serve in guiding further experiments and in analyzing the data to gain deep insight into various kinetic processes involved in translation.Comment: Minor revisio