The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Study of the retinoic acid regulated genes in the rodent hypothalamus controlling growth and appetite and the potential for the epigenetic control

Dissertação de mestrado em Bioquímica (área de especialização em Biomedicina)

Differential top-antitop cross-section measurements as a function of observables constructed from final-state particles using pp collisions at s√=7 TeV in the ATLAS detector

Various differential cross-sections are measured in top-quark pair (tt¯) events produced in proton--proton collisions at a centre-of-mass energy of s√=7 TeV at the LHC with the ATLAS detector. These differential cross-sections are presented in a data set corresponding to an integrated luminosity of 4.6 fb−1. The differential cross-sections are presented in terms of kinematic variables of a top-quark proxy referred to as the pseudo-top-quark whose dependence on theoretical models is minimal. The pseudo-top-quark can be defined in terms of either reconstructed detector objects or stable particles in an analogous way. The measurements are performed on tt¯ events in the lepton+jets channel, requiring exactly one charged lepton and at least four jets with at least two of them tagged as originating from a b-quark. The hadronic and leptonic pseudo-top-quarks are defined via the leptonic or hadronic decay mode of the W boson produced by the top-quark decay in events with a single charged lepton.The cross-section is measured as a function of the transverse momentum and rapidity of both the hadronic and leptonic pseudo-top-quark as well as the transverse momentum, rapidity and invariant mass of the pseudo-top-quark pair system. The measurements are corrected for detector effects and are presented within a kinematic range that closely matches the detector acceptance. Differential cross-section measurements of the pseudo-top-quark variables are compared with several Monte Carlo models that implement next-to-leading order or leading-order multi-leg matrix-element calculations.

Measurement of the tt¯ production cross-section as a function of jet multiplicity and jet transverse momentum in 7 TeV proton--proton collisions with the ATLAS detector

The tt¯ production cross-section dependence on jet multiplicity and jet transverse momentum is reported for proton--proton collisions at a centre-of-mass energy of 7 TeV in the single-lepton channel. The data were collected with the ATLAS detector at the CERN Large Hadron Collider and comprise the full 2011 data sample corresponding to an integrated luminosity of 4.6 fb−1. Differential cross-sections are presented as a function of the jet multiplicity for up to eight jets using jet transverse momentum thresholds of 25, 40, 60, and 80 GeV, and as a function of jet transverse momentum up to the fifth jet. The results are shown after background subtraction and corrections for all detector effects, within a kinematic range closely matched to the experimental acceptance. Several QCD-based Monte Carlo models are compared with the results. Sensitivity to the parton shower modelling is found at the higher jet multiplicities, at high transverse momentum of the leading jet and in the transverse momentum spectrum of the fifth leading jet. The MC@NLO+HERWIG MC is found to predict too few events at higher jet multiplicities.

Nonparametric estimation of the survival function for ordered multivariate failure time data: a comparative study

In longitudinal studies of disease, patients may experience several events through a follow-up period. In these studies, the sequentially ordered events are often of interest and lead to problems that have received much attention recently. Issues of interest include the estimation of bivariate survival, marginal distributions and the conditional distribution of gap times. In this work we consider the estimation of the survival function conditional to a previous event. Different nonparametric approaches will be considered for estimating these quantities, all based on the Kaplan-Meier estimator of the survival function. We explore the finite sample behavior of the estimators through simulations. The different methods proposed in this article are applied to a data set from a German Breast Cancer Study. The methods are used to obtain predictors for the conditional survival probabilities as well as to study the influence of recurrence in overall survival.

From the periphery to the brain: Lipocalin-2, a friend or foe?

Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided.

Single-function approach to calibrating whatman n.º 42 filter paper based on suction versus water content relationships

Several suction–water-content (s-w) calibrations for the filter paper method (FPM) used for soil-suction measurement have been published. Most of the calibrations involve a bilinear function (i.e., two different equations) with an inflection point occurring at 60 kPafunction with a smooth transition between the high and low suctions based on a regression analysis of various previously published calibrations obtained for filter paper Whatman No. 42 (W42) is presented and discussed. The approach is applied herein to data obtained from three establish bilinear calibrations (six equations) for W42 filter paper to determine the two fitting parameters of the continuous function. An experimental evaluation of the new calibration show that the suctions estimated by the contact FPM test using the proposed function compare well with suctions measured by other laboratory techniques for two different soils for the suction range of 50 kPa

Molecular regulation of flowering induction in Quercus suber

Dissertação de mestrado em Plant Molecular Biology, Biotechnology and Bioentrepeneurship

Exploring the role of O-Mannosylation in the modulation of E-Cadherin function in Gastric Cancer cell line models

Dissertação de mestrado em Bioquímica Aplicada – Biomedicina

Composition and structure variation for magnetron sputtered tantalum oxynitride thin films, as function of deposition parameters

Tantalum oxynitride thin films were produced by magnetron sputtering. The films were deposited usinga pure Ta target and a working atmosphere with a constant N2/O2ratio. The choice of this constant ratiolimits the study concerning the influence of each reactive gas, but allows a deeper understanding of theaspects related to the affinity of Ta to the non-metallic elements and it is economically advantageous.This work begins by analysing the data obtained directly from the film deposition stage, followed bythe analysis of the morphology, composition and structure. For a better understanding regarding theinfluence of the deposition parameters, the analyses are presented by using the following criterion: thefilms were divided into two sets, one of them produced with grounded substrate holder and the otherwith a polarization of −50 V. Each one of these sets was produced with different partial pressure of thereactive gases P(N2+ O2). All the films exhibited a O/N ratio higher than the N/O ratio in the depositionchamber atmosphere. In the case of the films produced with grounded substrate holder, a strong increaseof the O content is observed, associated to the strong decrease of the N content, when P(N2+ O2) is higherthan 0.13 Pa. The higher Ta affinity for O strongly influences the structural evolution of the films. Grazingincidence X-ray diffraction showed that the lower partial pressure films were crystalline, while X-rayreflectivity studies found out that the density of the films depended on the deposition conditions: thehigher the gas pressure, the lower the density. Firstly, a dominant -Ta structure is observed, for lowP(N2+ O2); secondly a fcc-Ta(N,O) structure, for intermediate P(N2+ O2); thirdly, the films are amorphousfor the highest partial pressures. The comparison of the characteristics of both sets of produced TaNxOyfilms are explained, with detail, in the text.

Goblet cell density association with tear function and ocular surface physiology

Purpose: To determine the relationship of goblet cell density (GCD) with tear function and ocular surface physiology. Methods: This was a cross-sectional study conducted in 35 asymptomatic subjects with mean age 23.8±3.6 years. Tear film assessment, conjunctiva and cornea examination were done in each subject. Conjunctival impression cytology was performed by applying Nitrocellulose Millipore MFTM-Membrane filter over the superior bulbar conjunctiva. The filter paper was than fixed with 96% ethanol and stained with Periodic Acid Schiff, Hematoxylin and Eosin. GCD was determined by optical microscopy. Relation between GCD and Schirmer score, tear break-up time (TBUT), bulbar redness, limbal redness and corneal staining was determined. Results: The mean GCD was 151±122 cells/mm2. GCD was found higher in eyes with higher Schirmer score but it was not significant (p = 0.75). There was a significant relationship ofGCDwith TBUT (p = 0.042). GCD was not correlated with bulbar redness (p = 0.126), and limbal redness (p = 0.054) as well as corneal staining (p = 0.079). No relationship of GCD with age and gender of the subjects (p > 0.05) was observed. Conclusion: GCD was found correlated with TBUT but no significant correlation was found with the aqueous portion of the tear, limbal as well as bulbar redness and corneal staining.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

Lack of the transcription factor hypoxia-inducible factor (HIF)-1α in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas

Accepted Manuscript

Semipermeable capsules wrapping a multifunctional and self-regulated co-culture microenvironment for osteogenic differentiation

A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the â stem cell nicheâ , the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.