Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitine

Methamphetamine (METH) is a powerful psychostimulant drug used worldwide for its reinforcing properties. In addition to the classic long-lasting monoaminergic-disrupting effects extensively described in the literature, METH has been consistently reported to increase blood brain barrier (BBB) permeability, both in vivo and in vitro, as a result of tight junction and cytoskeleton disarrangement. Microtubules play a critical role in cell stability, which relies on post-translational modifications such as a-tubulin acetylation. As there is evidence that psychostimulants drugs modulate the expression of histone deacetylases (HDACs), we hypothesized that in endothelial cells METH-mediation of cytoplasmatic HDAC6 activity could affect tubulin acetylation and further contribute to BBB dysfunction. To validate our hypothesis, we exposed the bEnd.3 endothelial cells to increasing doses of METH and verified that itleads to an extensivea-tubulin deacetylation mediated by HDACs activation. Furthermore, since we recently reported that acetyl-L-carnitine (ALC), a natural occurring compound, prevents BBB structural loss in a context of METH exposure, we reasoned that ALC could also preserve the acetylation of microtubules under METH action. The present results confirm that ALC is able to prevent METH-induced deacetylation providing effective protection on microtubule acetylation. Although further investigation is still needed, HDACs regulation may become a new therapeutic target for ALC.

Estágio no Departamento Financeiro do Município de Penafiel

Relatório de estágio para obtenção do grau de mestre em Finanças Empresariais

Activation timing of soleus and tibialis anterior muscles during sit-to-stand and stand to sit in post-stroke vs healthy subjects

O documento em anexo encontra-se na versão post-print (versão corrigida pelo editor).

Soleus activity in post-stroke subjects: movement sequence from standing to sitting

O documento em anexo encontra-se na versão post-print (versão corrigida pelo editor).

The Greatest lover: a post-colonial rewriting of My Fair Lady

INTRODUCTION The popular Hong Kong comedy, The Greatest Lover, re-incarnates one of the most popular western musicals, My Fair Lady. OBJECTIVES 1. To find out in what major ways My Fair Lady was rewritten as the Hong Kong Cantonese movie, Gungzi Docing (The Greatest Lover). 2. To find out the socio-political, socio-linguistic, and gender ideology behind the rewriting. METHODOLOGY 1. To note the similarity of the themes for both works – a creator falling in love with his/her creation, and class prejudice and cross-class romance. 2. To note how the times of The Greatest Lover differ from that of My Fair Lady. 3. To note how the main characters in The Greatest Lover differ from My Fair Lady in terms of profession, gender, etc. 4. To note how the plot of The Greatest Lover differs from that of My Fair Lady. 5. To note how focus on language in The Greatest Lover compares with that in My Fair Lady. 6. To discuss the ideological implications of the differences noted above, e.g. women in Hong Kong today have much higher status than women in Victorian England; the conflict between local Hong Kong people and both legal and illegal immigrants from Mainland China is even more serious than that between the British upper middle class and the lower class during the Victorian period. 7. Andre Lefevere (1992) argues that translation and adaptation are rewriting informed and influenced by the rewriter’s ideology, among other things. 8. Both Aline Remael (1995) and Patrick Cattrysse (1992) think that film adaptation is a kind of translation. 9. Sirkkus Aaltonen (2000) argues that drama translation mirrors the ideologies of the target society. CONCLUSION 1. The Greatest Lover projects local cultural significance onto My Fair Lady by helping us to appreciate an important Western work of art through the Hong Kong Cantonese perspective. 2. Broader issues in translation and intercultural studies are also considered.

Post-surgical wound infections involving Enterobacteriaceae with reduced susceptibility to ß-lactams in two Portuguese hospitals

The post-surgical period is often critical for infection acquisition. The combination of patient injury and environmental exposure through breached skin add risk to pre-existing conditions such as drug or depressed immunity. Several factors such as the period of hospital staying after surgery, base disease, age, immune system condition, hygiene policies, careless prophylactic drug administration and physical conditions of the healthcare centre may contribute to the acquisition of a nosocomial infection. A purulent wound can become complicated whenever antimicrobial therapy becomes compromised. In this pilot study, we analysed Enterobacteriaceae strains, the most significant gram-negative rods that may occur in post-surgical skin and soft tissue infections (SSTI) presenting reduced β-lactam susceptibility and those presenting extended-spectrum β-lactamases (ESBL). There is little information in our country regarding the relationship between β-lactam susceptibility, ESBL and development of resistant strains of microorganisms in SSTI. Our main results indicate Escherichia coli and Klebsiella spp. are among the most frequent enterobacteria (46% and 30% respectively) with ESBL production in 72% of Enterobacteriaceae isolates from SSTI. Moreover, coinfection occurred extensively, mainly with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (18% and 13%, respectively). These results suggest future research to explore if and how these associations are involved in the development of antibiotic resistance.

Processing XML with Java – a performance benchmark

Over time, XML markup language has acquired a considerable importance in applications development, standards definition and in the representation of large volumes of data, such as databases. Today, processing XML documents in a short period of time is a critical activity in a large range of applications, which imposes choosing the most appropriate mechanism to parse XML documents quickly and efficiently. When using a programming language for XML processing, such as Java, it becomes necessary to use effective mechanisms, e.g. APIs, which allow reading and processing of large documents in appropriated manners. This paper presents a performance study of the main existing Java APIs that deal with XML documents, in order to identify the most suitable one for processing large XML files

Performance analysis of Java APIS for XML processing

Over time, XML markup language has acquired a considerable importance in applications development, standards definition and in the representation of large volumes of data, such as databases. Today, processing XML documents in a short period of time is a critical activity in a large range of applications, which imposes choosing the most appropriate mechanism to parse XML documents quickly and efficiently. When using a programming language for XML processing, such as Java, it becomes necessary to use effective mechanisms, e.g. APIs, which allow reading and processing of large documents in appropriated manners. This paper presents a performance study of the main existing Java APIs that deal with XML documents, in order to identify the most suitable one for processing large XML files.

ECG denoising based on adaptive signal processing technique

An Electrocardiogram (ECG) monitoring system deals with several challenges related with noise sources. The main goal of this text was the study of Adaptive Signal Processing Algorithms for ECG noise reduction when applied to real signals. This document presents an adaptive ltering technique based on Least Mean Square (LMS) algorithm to remove the artefacts caused by electromyography (EMG) and power line noise into ECG signal. For this experiments it was used real noise signals, mainly to observe the di erence between real noise and simulated noise sources. It was obtained very good results due to the ability of noise removing that can be reached with this technique. A recolha de sinais electrocardiogr a cos (ECG) sofre de diversos problemas relacionados com ru dos. O objectivo deste trabalho foi o estudo de algoritmos adaptativos para processamento digital de sinal, para redu c~ao de ru do em sinais ECG reais. Este texto apresenta uma t ecnica de redu c~ao de ru do baseada no algoritmo Least Mean Square (LMS) para remo c~ao de ru dos causados quer pela actividade muscular (EMG) quer por ru dos causados pela rede de energia el ectrica. Para as experiencias foram utilizados ru dos reais, principalmente para aferir a diferen ca de performance do algoritmo entre os sinais reais e os simulados. Foram conseguidos bons resultados, essencialmente devido as excelentes caracter sticas que esta t ecnica tem para remover ru dos.

Mismatch negativity in childhood temporal lobe epilepsy: a proposed paradigm for testing central auditory processing

Background: Temporal lobe epilepsy (TLE) is a neurological disorder that directly affects cortical areas responsible for auditory processing. The resulting abnormalities can be assessed using event-related potentials (ERP), which have high temporal resolution. However, little is known about TLE in terms of dysfunction of early sensory memory encoding or possible correlations between EEGs, linguistic deficits, and seizures. Mismatch negativity (MMN) is an ERP component – elicited by introducing a deviant stimulus while the subject is attending to a repetitive behavioural task – which reflects pre-attentive sensory memory function and reflects neuronal auditory discrimination and perceptional accuracy. Hypothesis: We propose an MMN protocol for future clinical application and research based on the hypothesis that children with TLE may have abnormal MMN for speech and non-speech stimuli. The MMN can be elicited with a passive auditory oddball paradigm, and the abnormalities might be associated with the location and frequency of epileptic seizures. Significance: The suggested protocol might contribute to a better understanding of the neuropsychophysiological basis of MMN. We suggest that in TLE central sound representation may be decreased for speech and non-speech stimuli. Discussion: MMN arises from a difference to speech and non-speech stimuli across electrode sites. TLE in childhood might be a good model for studying topographic and functional auditory processing and its neurodevelopment, pointing to MMN as a possible clinical tool for prognosis, evaluation, follow-up, and rehabilitation for TLE.

Temporal lobe epilepsy in childhood – a study model of auditory processing

TLE in infancy has been the subject of varied research. Topographical and structural evidence is coincident with the neuronal systems responsible for auditory processing of the highest specialization and complexity. Recent studies have been showing the need of a hemispheric asymmetry for an optimization in central auditory processing (CAP) and acquisition and learning of a language system. A new functional research paradigm is required to study mental processes that require methods of cognitive-sensory information analysis processed in very short periods of time (msec), such as the ERPs. Thus, in this article, we hypothesize that the TLE in infancy could be a good model for topographic and functional study of CAP and its development process, contributing to a better understanding of the learning difficulties that children with this neurological disorder have.

Nutritional value and influence of the thermal processing on a traditional Portuguese fermented sausage (alheira)

Alheiras are a traditional, smoked, fermented meat sausage, produced in Portugal, with an undeniable cultural and gastronomic legacy. In this study, we assessed the nutritional value of this product, as well as the influence of different types of thermal processing. Alheiras from Mirandela were submitted to six different procedures: microwave, skillet, oven, charcoal grill, electric fryer and electric grill. Protein, fat, carbohydrate, minerals, NaCl, and cholesterol contents, as well as fatty acid profile were evaluated. The results show that alheiras are not hypercaloric but an unbalanced foodstuff (high levels of proteins and lipids) and the type of processing has a major impact on their nutritional value. Charcoal grill is the healthiest option: less fat (12.5 g/100 g) and cholesterol (29.3 mg/100 g), corresponding to a lower caloric intake (231.8 kcal, less 13% than the raw ones). Inversely, fried alheiras presented the worst nutritional profile, with the highest levels of fat (18.1 g/100 g) and cholesterol (76.0 g/100 g).

Anticipatory postural adjustments during sitting reach movement in post-stroke subjects

The study assessed the effect of velocity of arm movement on the generation of APAs in the contralateral and ipsilateral muscles of individuals with stroke in the sitting position. In the sitting position, 10 healthy and 8 post-stroke subjects reached for an object placed at the scapular plane and mid-sternum height at self-selected and fast velocities. Electromyography was recorded from the anterior deltoid (AD), upper (UT) and lower trapezius (LT), and latissimus dorsi (LD). Kinematic analysis was used to assess peak velocity and trunk displacement. Post-stroke subjects presented a delay of APAs on both sides of the body compared to healthy subjects. Differences were found between the timing of APAs on the ipsilateral and contralateral LD and LT in both movement speeds and in the ipsilateral UT during movement of the non-affected arm at a self-selected velocity. A delay in the contralateral LD in the reaching movement with the non-affected arm at fast velocity was also observed. Trunk displacement was greater in post-stroke subjects. In the sitting position, APAs were delayed in both fast and self-selected movements on both sides in post-stroke subjects, which also presented a higher trunk displacement.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study

BACKGROUND: Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. OBJECTIVE: The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed.METHODS: The effect of emotional valence and visualization types and their interaction were analyzed through a 3x2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. RESULTS: The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. CONCLUSIONS: This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios’ valence) and their interaction with three-dimensionality.