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.

Assessing the application of polypropylene multifilament yarns in brain phantoms

The currently available clinical imaging methods do not provide highly detailed information about location and severity of axonal injury or the expected recovery time of patients with traumatic brain injury [1]. High-Definition Fiber Tractography (HDFT) is a novel imaging modality that allows visualizing and quantifying, directly, the degree of axons damage, predicting functional deficits due to traumatic axonal injury and loss of cortical projections. This imaging modality is based on diffusion technology [2]. The inexistence of a phantom able to mimic properly the human brain hinders the possibility of testing, calibrating and validating these medical imaging techniques. Most research done in this area fails in key points, such as the size limit reproduced of the brain fibers and the quick and easy reproducibility of phantoms [3]. For that reason, it is necessary to develop similar structures matching the micron scale of axon tubes. Flexible textiles can play an important role since they allow producing controlled packing densities and crossing structures that match closely the human crossing patterns of the brain. To build a brain phantom, several parameters must be taken into account in what concerns to the materials selection, like hydrophobicity, density and fiber diameter, since these factors influence directly the values of fractional anisotropy. Fiber cross-section shape is other important parameter. Earlier studies showed that synthetic fibrous materials are a good choice for building a brain phantom [4]. The present work is integrated in a broader project that aims to develop a brain phantom made by fibrous materials to validate and calibrate HDFT. Due to the similarity between thousands of hollow multifilaments in a fibrous arrangement, like a yarn, and the axons, low twist polypropylene multifilament yarns were selected for this development. In this sense, extruded hollow filaments were analysed in scanning electron microscope to characterize their main dimensions and shape. In order to approximate the dimensional scale to human axons, five types of polypropylene yarns with different linear density (denier) were used, aiming to understand the effect of linear density on the filament inner and outer areas. Moreover, in order to achieve the required dimensions, the polypropylene filaments cross-section was diminished in a drawing stage of a filament extrusion line. Subsequently, tensile tests were performed to characterize the mechanical behaviour of hollow filaments and to evaluate the differences between stretched and non-stretched filaments. In general, an increase of the linear density causes the increase in the size of the filament cross section. With the increase of structure orientation of filaments, induced by stretching, breaking tenacity increases and elongation at break decreases. The production of hollow fibers, with the required characteristics, is one of the key steps to create a brain phantom that properly mimics the human brain that may be used for the validation and calibration of HDFT, an imaging approach that is expected to contribute significantly to the areas of brain related research.

Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

This paper reviews and extends searches for the direct pair production of the scalar supersymmetric partners of the top and bottom quarks in proton--proton collisions collected by the ATLAS collaboration during the LHC Run 1. Most of the analyses use 20 fb−1 of collisions at a centre-of-mass energy of s√=8 TeV, although in some case an additional 4.7 fb−1 of collision data at s√=7 TeV are used. New analyses are introduced to improve the sensitivity to specific regions of the model parameter space. Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models.

A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

The bounds of education in the human brain connectome

Inter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.

Logificação da Psicologia o itinerário intelectual de Edmundo Curvelo sobre a Mente, a Lógica e a Filosofia

Tese de Doutoramento em Filosofia - Especialidade de Filosofia da Mente

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

Tese de Doutoramento em Ciências da Saúde

Synthesis and biological evaluation of mono and bis-naphthalimide derivatives against SH-SY5Y, human brain cancer cells

Dissertação de mestrado em Medicinal Chemistry

Sleep during the third trimester of pregnancy: the role of depression and anxiety

Depression has been associated with sleep disturbances in pregnancy; however, no previous research has controlled the possible confounding effect of anxiety on this association. This study aims to analyze the effect of depression on sleep during the third trimester of pregnancy controlling for anxiety. The sample was composed by 143 depressed (n = 77) and non-depressed (n = 66) pregnant women who completed measures of depression, anxiety, and sleep. Differences between groups in sleep controlling for anxiety were found. Depressed pregnant women present higher number of nocturnal awakenings and spent more hours trying falling asleep during the night and the entire 24 h period. Present findings point out the effect of depression on sleep in late pregnancy, after controlling for anxiety.

Mother's anxiety and depression during the third pregnancy trimester and neonate's mother versus stranger's face/voice visual preference

Background: Neonates show visual preference for their mother's face/voice and shift their attention from their mother to a stranger's face/voice after habituation. Aim: To assess neonate's mother versus stranger's face/voice visual preference, namely mother's anxiety and depression during the third pregnancy trimester and neonate's: 1) visual preference for the mother versus the stranger's face/voice (pretest visual preference), 2) habituation to the mother's face/voice and 3) visual preference for the stranger versus the mother's face/voice (posttest visual preference). Method: Mothers (N=100) filled out the Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI) both at the third pregnancy trimester and childbirth, and the “preference and habituation to the mother's face/voice versus stranger” paradigm was administered to their newborn 1 to 5 days after childbirth. Results: Neonates of anxious/depressed mothers during the third pregnancy trimester contrarily to neonates of non-anxious/non-depressed mothers did not look 1) longer at their mother's than at the stranger's face/voice at the pretest visual preference (showing no visual preference for the mother), nor 2) longer at the stranger's face/voice in the posttest than in the pretest visual preference (not improving their attention to the stranger's after habituation). Conclusion: Infants exposed to mother's anxiety/depression at the third gestational trimester exhibit less perceptual/social competencies at birth.