Measurements of the nuclear modification factor for jets in Pb+Pb collisions at sNN =2.76TeV with the ATLAS detector

Measurements of inclusive jet production are performed in pp and Pb+Pb collisions at sNN−−−√=2.76 TeV with the ATLAS detector at the LHC, corresponding to integrated luminosities of 4.0 pb−1 and 0.14 nb−1 , respectively. The jets are identified with the anti-kt algorithm with R=0.4, and the spectra are measured over the kinematic range of jet transverse momentum 32factor, RAA, is evaluated and jets are found to be suppressed by approximately a factor of two in central collisions compared to pp collisions. The RAA shows a slight increase with pT and no significant variation with rapidity.

Exploring female mice interstrain differences relevant for models of depression

Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.

Female hippocampus vulnerability to environmental stress, a precipitating factor in tau aggregation pathology

Tau-mediated neurodegeneration is a central event in Alzheimer's disease (AD) and other tauopathies. Consistent with suggestions that lifetime stress may be a clinically-relevant precipitant of AD pathology, we previously showed that stress triggers tau hyperphosphorylation and accumulation; however, little is known about the etiopathogenic interaction of chronic stress with other AD risk factors, such as sex and aging. This study focused on how these various factors converge on the cellular mechanisms underlying tau aggregation in the hippocampus of chronically stressed male and female (middle-aged and old) mice expressing the most commonly found disease-associated Tau mutation in humans, P301L-Tau. We report that environmental stress triggers memory impairments in female, but not male, P301L-Tau transgenic mice. Furthermore, stress elevates levels of caspase-3-truncated tau and insoluble tau aggregates exclusively in the female hippocampus while it also alters the expression of the molecular chaperones Hsp90, Hsp70, and Hsp105, thus favoring accumulation of tau aggregates. Our findings provide new insights into the molecular mechanisms through which clinically-relevant precipitating factors contribute to the pathophysiology of AD. Our data point to the exquisite sensitivity of the female hippocampus to stress-triggered tau pathology.

Exploring the factor structure of neurocognitive measures in older individuals

Here we focus on factor analysis from a best practices point of view, by investigating the factor structure of neuropsychological tests and using the results obtained to illustrate on choosing a reasonable solution. The sample (n=1051 individuals) was randomly divided into two groups: one for exploratory factor analysis (EFA) and principal component analysis (PCA), to investigate the number of factors underlying the neurocognitive variables; the second to test the "best fit" model via confirmatory factor analysis (CFA). For the exploratory step, three extraction (maximum likelihood, principal axis factoring and principal components) and two rotation (orthogonal and oblique) methods were used. The analysis methodology allowed exploring how different cognitive/psychological tests correlated/discriminated between dimensions, indicating that to capture latent structures in similar sample sizes and measures, with approximately normal data distribution, reflective models with oblimin rotation might prove the most adequate.

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-a or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.

Algumas considerações sobre o princípio da culpa enquanto factor de autonomização do Direito das Contra-ordenações

Dissertação de mestrado em Direito Judiciário

Desarrollo de una técnica de detección rápida y precisa de preñez en cerdos. Segunda etapa: Purificación de factor precoz de preñez y desarrollo de un radioinmunoensayo

Una de las principales causas de pérdida reproductiva en condiciones normales, es la mortalidad embrionaria basal. Por lo tanto, estaría ampliamente justificado el diseño de experiencias que nos permitan encontrar las causas de las pérdidas y detectar la preñez tan precozmente, como fuere posible. Las causas de las pérdidas embrionarias en muchos casos se relacionan con fallas en las señales del embrión dirigidas a la madre con el fin de establecer inmunotolerancia, fenómeno imprescindible para la sobrevida del embrión porque modifica la respuesta inmune de modo favorable para éste. La inmunomodulación es ejercida por sustancias de naturaleza proteica detectadas durante la gestación. Entre estas se encuentra el Factor Precoz de Preñez (EPF). Durante la preñez, el EPF tiene dos fuentes de producción: una materna y otra embrionaria. El EPF materno, también llamado temprano, se produce durante los períodos pre y periimplantacional y persiste hasta el último tercio de la preñez. Hasta el presente, la única técnica desarrollada para la detección del EPF, es un ensayo in vitro propuesto por Morton que mide de manera indirecta la actividad del factor. Dicha técnica se basa en la capacidad que tiene el EPF de potenciar la acción de un suero antilinfocitario (SAL), para inhibir la formación de rosetas entre linfocitos T y eritrocitos heterólogos en presencia de complemento. Esta técnica es efectiva pero muy compleja para realizarse rutinariamente en el laboratorio. De todo lo expuesto surge claramente la necesidad del aislamiento y purificación del EPF, lo que permitiría desarrollar metodologías inmunológicas aplicables para el diagnóstico de rutina de detección de preñez en cerdos y un notable adelanto en el estudio de alguno de los factores que afectan los sucesos de concepción y el curso de preñez, momentos claves en la fisiología reproductiva. Objetivos Generales - Desarrollar una técnica de detección rápida y precisa del Factor Precoz de Preñez (EPF) en cerdos. Objetivos Específicos - Aislar, purificar y caracterizar al Factor Precoz de Preñez (EPF) a partir de suero y placenta de cerdas gestantes. - Obtener y valorar un antisuero policlonal anti-EPF en conejos a partir de la fracción purificada con mayor índice de actividad EPF.

Jacob - an activity regulated morphogenetic factor for synapto-dendritic cytoarchitecture

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2008

Modulation of the activity of the mitochondrial BK-channel and the permeability transition pore by hypoxia and apoptotic factors

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Cross-talk of protein kinase B (PKB/Akt) with the transcription factor NFAT and the Src kinase Fyn in T lymphocytes

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Modulation of [My]-opioid receptor signal transduction and endocytosis by ADP-ribosylation factor proteins

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Konstruktion einer nicht-IGF-bindenden Insulin-like Growth Factor Binding Protein-2-Variante und Untersuchung ihrer Wirkung auf das Tumorzellwachstum

Magdeburg, Univ., Medizin. Fakultät, Diss., 2008

Regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-[kappa]B) by protein Kinase C theta (PKC-[theta]) and cylindromatosis (CYLD) in murine listeriosis and toxoplasmosis

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2013

Width-weight relationship and condition factor of Ucides cordatus (Crustacea, Decapoda, Ucididae) at tropical mangroves of Northeast Brazil

The present contribution aims at evaluating the carapace width vs. humid weight relationship and the condition factor of Ucides cordatus (Linnaeus, 1763), in the mangrove forests of the Ariquindá and Mamucabas rivers, state of Pernambuco, Brazil. These two close areas present similar characteristics of vegetation and substrate, but exhibit different degrees of environmental conservation: the Ariquindá River is the preserved area, considered one of the last non-polluted of Pernambuco, while the Mamucabas River suffers impacts from damming, deforestation and deposition of waste. A total of 1,298 individuals of U. cordatus were collected. Males were larger and heavier than females, what is commonly observed in Brachyura. Ucides cordatus showed allometric negative growth (p < 0.05), which is probably related to the dilatation that this species develops in the lateral of the carapace, which stores six pairs of gills. The values of b were within the limit established for aquatic organisms. Despite of the condition factor being considered an important feature to confirm the reproductive period, since it varies with cyclic activities, in the present study it was not correlated to the abundance of ovigerous females. However, it was considered a good parameter to evaluate environmental impacts, being significantly lower at the impacted area.