The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

Effector memory CD4+ T cells are associated with cognitive performance in a senior population

Objective: Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. Methods: In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Results: Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account. Conclusions: This is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.

Bioactive nanocomposite spheres with proved shape memory capability in bone defects

Bioactive glass nanoparticles (BGNPs) promote an apatite surface layer in physiologic conditions that lead to a good interfacial bonding with bone.1 A strategy to induce bioactivity in non-bioactive polymeric biomaterials is to incorporate BGNPs in the polymer matrix. This combination creates a nanocomposite material with increased osteoconductive properties. Chitosan (CHT) is a polymer obtained by deacetylation of chitin and is biodegradable, non-toxic and biocompatible. The combination of CHT and the BGNPs aims at designing biocompatible spheres promoting the formation of a calcium phosphate layer at the nanocomposite surface, thus enhancing the osteoconductivity behaviour of the biomaterial. Shape memory polymers (SMP) are stimuli-responsive materials that offer mechanical and geometrical action triggered by an external stimulus.2 They can be deformed and fixed into a temporary shape which remains stable unless exposed to a proper stimulus that triggers recovery of their original shape. This advanced functionality makes such SMPs suitable to be implanted using minimally invasive surgery procedures. Regarding that, the inclusion of therapeutic molecules becomes attractive.  We propose the synthesis of shape memory bioactive nanocomposite spheres with drug release capability.3   1.  L. L. Hench, Am. Ceram. Soc. Bull., 1993, 72, 93-98. 2.  A. Lendlein and S. Kelch, Angew Chem Int Edit, 2002, 41, 2034-2057. 3.  Ã . J. Leite, S. G. Caridade and J. F. Mano, Journal of Non-Crystalline Solids (in Press)

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

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.

Connecting free volume with shape memory properties in noncytotoxic gamma-irradiated polycyclooctene

The free volume holes of a shape memory polymer have been analysed considering that the empty space between molecules is necessary for the molecular motion, and the shape memory response is based on polymer segments acting as molecular switches through variable flexibility with temperature or other stimuli. Therefore, thermomechanical analysis (TMA) and positron annihilation lifetime spectroscopy (PALS) have been applied to analyse shape recovery and free volume hole sizes in gamma irradiated polycyclooctene (PCO) samples, as a non-cytotoxic alternative to more conventional PCO crosslinked via peroxide for future applications in medicine. Thus, a first approach relating structure, free volume holes and shape memory properties in gamma irradiated PCO is presented. The results suggest that free volume holes caused by gamma irradiation in PCO samples facilitate the recovery process by improving movement of polymer chains and open t possibilities for the design and control of the macroscopic response.

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.

Learning joint representations for order and timing of perceptual-motor sequences: a dynamic neural field approach

Many of our everyday tasks require the control of the serial order and the timing of component actions. Using the dynamic neural field (DNF) framework, we address the learning of representations that support the performance of precisely time action sequences. In continuation of previous modeling work and robotics implementations, we ask specifically the question how feedback about executed actions might be used by the learning system to fine tune a joint memory representation of the ordinal and the temporal structure which has been initially acquired by observation. The perceptual memory is represented by a self-stabilized, multi-bump activity pattern of neurons encoding instances of a sensory event (e.g., color, position or pitch) which guides sequence learning. The strength of the population representation of each event is a function of elapsed time since sequence onset. We propose and test in simulations a simple learning rule that detects a mismatch between the expected and realized timing of events and adapts the activation strengths in order to compensate for the movement time needed to achieve the desired effect. The simulation results show that the effector-specific memory representation can be robustly recalled. We discuss the impact of the fast, activation-based learning that the DNF framework provides for robotics applications.

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.

Enhanced resistive switching and multilevel behavior in bilayered HfAlO/HfAlOx structures for non-volatile memory applications

In this work, hafnium aluminum oxide (HfAlO) thin films were deposited by ion beam sputtering deposition technique on Si substrate. The presence of oxygen vacancies in the HfAlOx layer deposited in oxygen deficient environment is evidenced from the photoluminescence spectra. Furthermore, HfAlO(oxygen rich)/HfAlOx(oxygen poor) bilayer structures exhibit multilevel resistive switching (RS), and the switching ratio becomes more prominent with increasing the HfAlO layer thickness. The bilayer structure with HfAlO/HfAlOx thickness of 30/40 nm displays the enhanced multilevel resistive switching characteristics, where the high resistance state/ intermediate resistance state (IRS) and IRS/low resistance state resistance ratios are 102 and 5 105 , respectively. The switching mechanisms in the bilayer structures were investigated by the temperature dependence of the three resistance states. This study revealed that the multilevel RS is attributed to the coupling of ionic conduction and the metallic conduction, being the first associated to the formation and rupture of conductive filaments related to oxygen vacancies and the second with the formation of a metallic filament. Moreover, the bilayer structures exhibit good endurance and stability in time.

Transcranial direct current stimulation based metaplasticity protocols in working memory

It has been already shown that delivering tDCS that are spaced by an interval alters its impact on motor plasticity. These effects can be explained, based on metaplasticity in which a previous modification of activity in a neuronal network can change the effects of subsequent interventions in the same network. But to date there is limited data assessing metaplasticity effects in cognitive functioning.

Abnormal interactions between context, memory structure, and mood in schizophrenia: an ERP investigation

This study used event-related potentials to examine interactions between mood, sentence context, and semantic memory structure in schizophrenia. Seventeen male chronic schizophrenia and 15 healthy control subjects read sentence pairs after positive, negative, or neutral mood induction. Sentences ended with expected words (EW), within-category violations (WCV), or between-category violations (BCV). Across all moods, patients showed sensitivity to context indexed by reduced N400 to EW relative to both WCV and BCV. However, they did not show sensitivity to the semantic memory structure. N400 abnormalities were particularly enhanced under a negative mood in schizophrenia. These findings suggest abnormal interactions between mood, context processing, and connections within semantic memory in schizophrenia, and a specific role of negative mood in modulating semantic processes in this disease.

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

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.