Elucidating the molecular mechanisms that underlie the target control of motoneuron death

Approximately half of the motoneurons generated during normal embryonic development undergo programmed cell death. Most of this death occurs during the time when synaptic connections are being formed between motoneurons and their target, skeletal muscle. Subsequent muscle activity stemming from this connection helps determine the final number of surviving motoneurons. These observations have given rise to the idea that motoneuron survival is dependent upon access to muscle derived trophic factors, presumably through intact neuromuscular synapses. However, it is not yet understood how the muscle regulates the supply of such trophic factors, or if there are additional mechanisms operating to control the fate of the innervating motoneuron. Recent observations have highlighted target independent mechanisms that also operate to support the survival of motoneurons, such as early trophic-independent periods of motoneuron death, trophic factors derived from Schwann cells and selection of motoneurons during pathfinding. Here we review recent investigations into motoneuron cell death when the molecular signalling between motoneurons and muscle has been genetically disrupted. From these studies, we suggest that in addition to trophic factors from muscle and/or Schwann cells, specific adhesive interactions between motoneurons and muscle are needed to regulate motoneuron survival. Such interactions, along with intact synaptic basal lamina, may help to regulate the supply and presentation of trophic factors to motoneurons.

Diverse synaptic mechanisms generate direction selectivity in the rabbit retina

The synaptic conductance of the On-Off direction-selective ganglion cells was measured during visual stimulation to determine whether the direction selectivity is a property of the circuitry presynaptic to the ganglion cells or is generated by postsynaptic interaction of excitatory and inhibitory inputs. Three synaptic asymmetries were identified that contribute to the generation of direction-selective responses: (1) a presynaptic mechanism producing stronger excitation in the preferred direction, (2) a presynaptic mechanism producing stronger inhibition in the opposite direction, and (3) postsynaptic interaction of excitation with spatially offset inhibition. Although the on- and off-responses showed the same directional tuning, the off-response was generated by all three mechanisms, whereas the on- response was generated primarily by the two presynaptic mechanisms. The results indicate that, within a single neuron, different strategies are used within distinct dendritic arbors to accomplish the same neural computation.

Lipid rafts and caveolae as portals for endocytosis: New insights and common mechanisms

Clathrin-coated pits and caveolae are two of the most recognizable features of the plasma membrane of mammalian cells. While our understanding of the machinery regulating and driving clathrin-coated pit-mediated endocytosis has progressed dramatically, including the elucidation of the structure of individual components and partial in vitro reconstitution, the role of caveolae as alternative endocytic carriers still remains elusive 50 years after their discovery. However, recent work has started to provide new insights into endocytosis by caveolae and into apparently related pathways involving lipid raft domains. These pathways, distinguished by their exquisite sensitivity to cholesterol-sequestering agents, can involve caveolae but also exist in cells devoid of caveolins and caveolae. This review examines the current evidence for the involvement of rafts and caveolae in endocytosis and the molecular players involved in their regulation.

Mechanisms of exercise training in patients with heart failure

Background The reduction of exercise capacity because of fatigue and dyspnea in patients with heart failure can be improved with exercise training. We sought to examine the mechanisms of exercise training, as an adjunctive treatment strategy for patients with heart failure. Methods a reviewed the published data on the possible mechanisms of effect of exercise training in heart failure. Results Symptoms of heart failure may be explained on the basis of abnormal skeletal muscle perfusion and structure and endothelial function. Exercise training has been shown to engender changes in muscle structure and biochemistry and vascular function, although effects on cardiac function have not been detected uniformly and may require longer training periods. Conclusions A suitable, long-term program of exercise training may reverse unfavorable interactions among the heart, vessels, and skeletal muscles. These improvements may be preserved with an ongoing maintenance program.

Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type 11 diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.

O instituto da ouvidoria como instrumento para a melhoria da gestão pública universitária: estudo de caso da ouvidoria geral da Universidade Federal do Espírito Santo

No âmbito da Democracia Participativa, cujos elementos foram inseridos na democracia brasileira pela Constituição Federal de 1988 (CF/88), ao legitimar a participação do usuário na administração pública direta e indireta, prevendo mecanismos de controle social, destacamos as ouvidorias públicas, e dentre elas as ouvidorias universitárias, como instrumentos de interlocução e intermediação entre os cidadãos e as instituições públicas. Embora existam importantes estudos acerca das ouvidorias públicas, sobretudo nas áreas da saúde e judiciária, ainda há escassez no campo da gestão pública quanto a estudos específicos sobre as ouvidorias universitárias, restando uma lacuna que necessita ser preenchida. Nesse sentido, a presente pesquisa teve o propósito de investigar a atuação da Ouvidoria Geral da Universidade Federal do Espírito Santo (UFES), buscando responder à seguinte questão: Qual a importância da Ouvidoria Geral da UFES na gestão pública dessa instituição? E, com isso, trazer à tona aspectos relevantes e peculiares das ouvidorias universitárias, que certamente alcançam, a exemplo da Ouvidoria Geral da UFES, ouvidorias de outras instituições públicas de ensino superior, dando maior visibilidade a um instituto por vezes desconhecido ou tratado sem a atenção devida. Para tanto, foi realizada uma pesquisa qualitativa a partir do procedimento técnico do estudo de caso, com utilização de análise documental, observação espontânea e aplicação de entrevistas. Assim, além de abordar aspectos estruturais e conjunturais que envolvem a Ouvidoria, esse estudo traz a percepção de cidadãos que utilizaram os serviços do órgão, propiciando a ampliação da discussão sobre o tema na Academia e, porventura, a indução de mudanças organizacionais.

ß-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Descoberta de conhecimento em Logs de tentativas de intrusão. Um estudo de caso em Instituições de Ensino Superior

Perante a evolução constante da Internet, a sua utilização é quase obrigatória. Através da web, é possível conferir extractos bancários, fazer compras em países longínquos, pagar serviços sem sair de casa, entre muitos outros. Há inúmeras alternativas de utilização desta rede. Ao se tornar tão útil e próxima das pessoas, estas começaram também a ganhar mais conhecimentos informáticos. Na Internet, estão também publicados vários guias para intrusão ilícita em sistemas, assim como manuais para outras práticas criminosas. Este tipo de informação, aliado à crescente capacidade informática do utilizador, teve como resultado uma alteração nos paradigmas de segurança informática actual. Actualmente, em segurança informática a preocupação com o hardware é menor, sendo o principal objectivo a salvaguarda dos dados e continuidade dos serviços. Isto deve-se fundamentalmente à dependência das organizações nos seus dados digitais e, cada vez mais, dos serviços que disponibilizam online. Dada a mudança dos perigos e do que se pretende proteger, também os mecanismos de segurança devem ser alterados. Torna-se necessário conhecer o atacante, podendo prever o que o motiva e o que pretende atacar. Neste contexto, propôs-se a implementação de sistemas de registo de tentativas de acesso ilícitas em cinco instituições de ensino superior e posterior análise da informação recolhida com auxílio de técnicas de data mining (mineração de dados). Esta solução é pouco utilizada com este intuito em investigação, pelo que foi necessário procurar analogias com outras áreas de aplicação para recolher documentação relevante para a sua implementação. A solução resultante revelou-se eficaz, tendo levado ao desenvolvimento de uma aplicação de fusão de logs das aplicações Honeyd e Snort (responsável também pelo seu tratamento, preparação e disponibilização num ficheiro Comma Separated Values (CSV), acrescentando conhecimento sobre o que se pode obter estatisticamente e revelando características úteis e previamente desconhecidas dos atacantes. Este conhecimento pode ser utilizado por um administrador de sistemas para melhorar o desempenho dos seus mecanismos de segurança, tais como firewalls e Intrusion Detection Systems (IDS).

Mechanisms for reflection-based monitoring of real- time systems

Monitoring is a very important aspect to consider when developing real-time systems. However, it is also important to consider the impact of the monitoring mechanisms in the actual application. The use of Reflection can provide a clear separation between the real-time application and the implemented monitoring mechanisms, which can be introduced (reflected) into the underlying system without changing the actual application part of the code. Nevertheless, controlling the monitoring system itself is still a topic of research. The monitoring mechanisms must contain knowledge about “how to get the information out”. Therefore, this paper presents the ongoing work to define a suitable strategy for monitoring real-time systems through the use of Reflection.

β-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This reviewalso summarizes the main resistancemechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Adding local priority-based dispatching mechanisms to P-NET networks: a fixed priority approach

In this paper we address the real-time capabilities of P-NET, which is a multi-master fieldbus standard based on a virtual token passing scheme. We show how P-NET’s medium access control (MAC) protocol is able to guarantee a bounded access time to message requests. We then propose a model for implementing fixed prioritybased dispatching mechanisms at each master’s application level. In this way, we diminish the impact of the first-come-first-served (FCFS) policy that P-NET uses at the data link layer. The proposed model rises several issues well known within the real-time systems community: message release jitter; pre-run-time schedulability analysis in non pre-emptive contexts; non-independence of tasks at the application level. We identify these issues in the proposed model and show how results available for priority-based task dispatching can be adapted to encompass priority-based message dispatching in P-NET networks.

On the use of code mobility mechanisms in real-time systems

Applications with soft real-time requirements can benefit from code mobility mechanisms, as long as those mechanisms support the timing and Quality of Service requirements of applications. In this paper, a generic model for code mobility mechanisms is presented. The proposed model gives system designers the necessary tools to perform a statistical timing analysis on the execution of the mobility mechanisms that can be used to determine the impact of code mobility in distributed real-time applications.

Collision-free beacon scheduling mechanisms for IEEE 802.15.4/Zigbee cluster-tree wireless sensor networks

The recently standardized IEEE 802.15.4/Zigbee protocol stack offers great potentials for ubiquitous and pervasive computing, namely for Wireless Sensor Networks (WSNs). However, there are still some open and ambiguous issues that turn its practical use a challenging task. One of those issues is how to build a synchronized multi-hop cluster-tree network, which is quite suitable for QoS support in WSNs. In fact, the current IEEE 802.15.4/Zigbee specifications restrict the synchronization in the beacon-enabled mode (by the generation of periodic beacon frames) to star-based networks, while it supports multi-hop networking using the peer-to-peer mesh topology, but with no synchronization. Even though both specifications mention the possible use of cluster-tree topologies, which combine multi-hop and synchronization features, the description on how to effectively construct such a network topology is missing. This paper tackles this problem, unveils the ambiguities regarding the use of the cluster-tree topology and proposes two collision-free beacon frame scheduling schemes. We strongly believe that the results provided in this paper trigger a significant step towards the practical and efficient use of IEEE 802.15.4/Zigbee cluster-tree networks.

Auxiliary mechanisms for telerobotics

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e de Computadores