Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Eph/Ephrin memhrane proteins: A mammalian expression vector pTIg-BOS-Fc allowing rapid protein purification

There is an urgent need for high purity, single chain, fully functional Eph/ephrin membrane proteins. This report outlines the pTIg-BOS-Fc vector and purification approach resulting in rapid increased production of fully functional single chain extracellular proteins that were isolated with high purity and used in structure-function analysis and pre-clinical studies.

Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers

Sustained delivery of heparin to the localized adventitial surface of grafted blood vessels has been shown to prevent the vascular smooth muscle cell (VSMC) proliferation that can lead to graft occlusion and failure. In this study heparin was incorporated into electrospun poly(epsilon-caprolactone) (PCL) fiber mats for assessment as a controlled delivery device. Fibers with smooth surfaces and no bead defects could be spun from polymer solutions with 8% w/v PCL in 7:3 dichloromethane: methanol. A significant decrease in fiber diameter was observed with increasing heparin concentration. Assessment of drug loading, and imaging of fluorescently labeled heparin showed homogenous distribution of heparin throughout the fiber mats. A total of approximately half of the encapsulated heparin was released by diffusional control from the heparin/PCL fibers after 14 days. The fibers did not induce an inflammatory response in macrophage cells in vitro and the released heparin was effective in preventing the proliferation of VSMCs in culture. These results suggest that electrospun PCL fibers are a promising candidate for delivery of heparin to the site of vascular injury. (C) 2005 Elsevier Ltd. All rights reserved.

Selective loss of synaptic proteins in Alzheimer's disease: Evidence for an increased severity with APOE epsilon 4

A pathological feature of Alzheimer's disease (AD) is an area-specific neuronal loss that may be caused by excitotoxicity-related synaptic dysfunction. Relative expression levels of synaptopbysin, dynamin I, complexins I and II, N-cadherin, and alpha CaMKII were analysed in human brain tissue from AD cases and controls in hippocampus, and inferior temporal and occipital cortices. Synaptophysin and dynamin I are presynaptic terminal proteins not specific to any neurotransmitter system whereas complexin II, N-cadherin, and alpha CaMKII are specific for excitatory synapses. Complexin I is a presynaptic protein localised to inhibitory synapses. There were no significant differences in synaptophysin, dynamin I, N-cadherin, or alpha CaMKII protein levels between AD cases and controls. The complexin proteins were both markedly lower in AD cases than in controls (P < 0.01). Cases were also categorised by APOE genotype. Averaged across areas there was a 36% lowering of presynaptic proteins in AD cases carrying at least one epsilon 4 allele compared with in AD cases lacking the epsilon 4 allele. We infer that synaptic protein level is not indicative of neuronal loss, but the synaptic dysfunction may result from the marked relative loss of the complexins in AD, and lower levels of presynaptic proteins in AD cases with the APOE epsilon 4 allele. (c) 2006 Elsevier Ltd. All rights reserved.

Real-Time Gene-Expression Extraction with Fast Classification (FC) Networks

Fast Classification (FC) networks were inspired by a biologically plausible mechanism for short term memory where learning occurs instantaneously. Both weights and the topology for an FC network are mapped directly from the training samples by using a prescriptive training scheme. Only two presentations of the training data are required to train an FC network. Compared with iterative learning algorithms such as Back-propagation (which may require many hundreds of presentations of the training data), the training of FC networks is extremely fast and learning convergence is always guaranteed. Thus FC networks may be suitable for applications where real-time classification is needed. In this paper, the FC networks are applied for the real-time extraction of gene expressions for Chlamydia microarray data. Both the classification performance and learning time of the FC networks are compared with the Multi-Layer Proceptron (MLP) networks and support-vector-machines (SVM) in the same classification task. The FC networks are shown to have extremely fast learning time and comparable classification accuracy.

RI MELHOR QUEM RI NA SALA DE AULA? UM ESTUDO SOBRE A PERCEPÇÃO DO RISO POR ALUNOS E PROFESSORES

Pouco discutido no âmbito pedagógico, o riso tem sido historicamente dissociado da escola, motivo pelo qual este trabalho tem como objetivo identificar como ele é percebido em sala de aula. A proposta é entender como o riso e sua função social são vistos por professores e alunos. Para isso, foi selecionada uma escola pública estadual na cidade de São Bernardo do Campo, SP. Lá são atendidos adolescentes que frequentam as aulas no Ensino Fundamental II e Médio. A pesquisa foi realizada com estudantes que estão terminando o Ensino Fundamental. Cem alunos responderam a questionários estruturados, compostos por itens de perfil e questões abertas. O mesmo foi feito com dezenove professores da referida escola, entretanto as questões para cada público sofreram variações. Como categoria analítica, foi utilizado o conceito de representação da Teoria de Representações Sociais, de forma instrumental. Os resultados obtidos indicam que os sujeitos observam um conceito híbrido presente na composição do objeto em análise, de forma que o avaliam ora como um elemento nocivo, ora como um recurso estimulante a aulas mais agradáveis. Foi constatado que os alunos riem na escola, mas é expressivo o fato de não associar essa ação ao contexto escolar. Os estudantes reforçam que o riso na sala de aula atrapalha a concentração, embora sejam conscientes de que essa constatação é circunstancial. Em contrapartida, mais de 60 alunos afirmaram já terem aprendido algo com a interferência do riso, sendo o professor o principal protagonista nesses momentos. Com relação aos docentes, a maioria afirmou que o riso pode ajudar o aluno a aprender algo, mas compreendem que a maior contribuição desse elemento na sala de aula é a de proporcionar um ambiente mais agradável. As duas desvantagens mais listadas pelos professores sobre o riso na sala de aula é a de que ele pode provocar a falta de atenção do aluno e também momentos de bullying entre os colegas de sala. Acredita-se que a associação do ambiente escolar com manifestações de seriedade justifique as frequentes referências feitas ao seu aspecto negativo, retratado na pesquisa pelos sujeitos. Mais da metade dos docentes analisa que o riso pode servir como instrumento pedagógico, entretanto os alunos afirmam que isso depende do professor e do momento. A pesquisa deixou evidente que o aspecto negativo do riso impede que este objeto seja mais bem aceito na escola, de forma que a percepção que os sujeitos fazem sobre o riso passa a interferir na relação que estabelecem com ele em sala de aula.

Ascorbate and α-tocopherol differentially modulate reactive oxygen species generation by neutrophils in response to FcγR and TLR agonists

Periodontitis, a ubiquitous chronic inflammatory disease, is associated with reduced antioxidant defences and neutrophil hyperactivity in terms of reactive oxygen species (ROS) generation. Its phenotype is thus characterized by oxidative stress. We have determined the effect of antioxidant micronutrients ascorbate and α-tocopherol on neutrophil ROS generation. Peripheral neutrophils from periodontally-healthy individuals (n = 20) were challenged with phorbol myristate acetate, IgG-opsonised Staphylococcus aureus, Fusobacterium nucleatum or PBS in the presence and absence of micronutrients (50 μM). Total and extracellular ROS were measured by luminol and isoluminol chemiluminescence respectively. Total and extracellular unstimulated, baseline ROS generation was unaffected by α-tocopherol, but inhibited by ascorbate and a combination of both micronutrients. Fcγ-receptor (Fcγ-R)-stimulated total or extracellular ROS generation was not affected by the presence of individual micronutrients. However, the combination significantly reduced extracellular FcγR-stimulated ROS release. Neither micronutrient inhibited TLR-stimulated total ROS, but the combination caused inhibition. Ascorbate and the micronutrient combination, but not α-tocopherol, inhibited extracellular ROS release by TLR-stimulated cells. Such micronutrient effects in vivo could be beneficial in reducing collateral tissue damage in chronic inflammatory diseases, such as periodontitis, while retaining immune-mediated neutrophil function. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Numerical and experimental analysis of sensitivity-enhanced RI sensor based on Ex-TFG in thin cladding fiber

We report a highly sensitive refractive index (RI) sensor in the aqueous solution, which is based on an 81°-tilted fiber grating structure inscribed into a thin cladding fiber with 40 μm cladding radius. The numerical analysis has indicated that the RI sensitivity of cladding resonance mode of the grating can be significantly enhanced with reducing cladding size. This has been proved by the experimental results as the RI sensitivities of TM and TE resonance peaks in the index region of 1.345 have been increased to 1180 nm/RIU and 1150 nm/RIU, respectively, from only 200 and 170 nm/RIU for the same grating structure inscribed in standard telecom fiber with 62.5-μm cladding radius. Although the temperature sensitivity has also increased, the change in temperature sensitivity is still insignificant in comparison with RI sensitivity enhancement.

Optical RI sensor based on an in-fiber bragg grating fabry-perot cavity embedded with a micro-channel

We report a linear response optical refractive index (RI) sensor, which is fabricated based on a micro-channel created within a Fabry Perot (F-P) cavity by chemical etching assisted by femtosecond laser inscription. The experimental results show the F-P resonance peak has a linear response with the RI of medium and the measuring sensitivity is proportion to the length of micro-channel. The sensor with 5 μm -long micro-channel exhibited an RI sensitivity of 1.15nm/RIU and this sensitivity increased to 9.08nm/RIU when widening the micro-channel to 35μm. Furthermore, such micro-channel FP sensors show a much broader RI sensing dynamic range (from 1.3 to 1.7) than other reported optical fiber sensors. © 2012 SPIE.

Experimental data of CO2, CO3, Omega calcite saturation, pH values, alpha and epsilon fractionation factors, and Dd18O calctite-water

The oxygen isotopic composition (d18O) of calcium carbonate of planktonic calcifying organisms is a key tool for reconstructing both past seawater temperature and salinity. The calibration of paloeceanographic proxies relies in general on empirical relationships derived from field experiments on extant species. Laboratory experiments have more often than not revealed that variables other than the target parameter influence the proxy signal, which makes proxy calibration a challenging task. Understanding these secondary or "vital" effects is crucial for increasing proxy accuracy. We present data from laboratory experiments showing that oxygen isotope fractionation during calcification in the coccolithophore Calcidiscus leptoporus and the calcareous dinoflagellate Thoracosphaera heimii is dependent on carbonate chemistry of seawater in addition to its dependence on temperature. A similar result has previously been reported for planktonic foraminifera, supporting the idea that the [CO3]2- effect on d18O is universal for unicellular calcifying planktonic organisms. The slopes of the d18O/[CO3]2- relationships range between -0.0243 per mil/(µmol/kg) (calcareous dinoflagellate T. heimii) and the previously published -0.0022 per mil/(µmol/kg) (non-symbiotic planktonic foramifera Orbulina universa), while C. leptoporus has a slope of -0.0048 per mil/(µmol/kg). We present a simple conceptual model, based on the contribution of d18O-enriched [HCO3]- to the [CO3]2- pool in the calcifying vesicle, which can explain the [CO3]2- effect on d18O for the different unicellular calcifiers. This approach provides a new insight into biological fractionation in calcifying organisms. The large range in d18O/[CO3]2- slopes should possibly be explored as a means for paleoreconstruction of surface [CO3]2-, particularly through comparison of the response in ecologically similar planktonic organisms.

10 year old runner Nancy Krolewski from the Liberty Athletic Club (RI)

General note: Title and date provided by Bettye Lane.