Ticks Take Cues from Mammalian Interferon

Interferons are considered a first line of immune defense restricted to vertebrates. In this issue of Cell Host & Microbe, Smith et al. (2016) demonstrate that mammalian interferon γ activates an antimicrobial response within ticks feeding on blood. The study suggests that arthropods have a parallel interferon-like defense system

Alterações do tecido muscular com o envelhecimento

Sarcopenia is characterized by a progressive generalized decrease of skeletal muscle mass, strength and function with aging. Recent- ly, the genetic determination has been associated with muscle mass and muscle strength in elderly. These two phenotypes of risk are the most commonly recognized and studied for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. It is well known that the development and maintenance of muscle mass in early adulthood reduces the risk of developing sarcopenia and leads to a healthy aging. For that reason it seems important to identify which genetic factors interact with aging and in particular with the musculoskeletal response to exercise in such individuals. This review is designed to summarize the most important and representative studies about the possible association between certain genetic polymorphisms and muscle phenotypes in older populations. Also we will focuses on nutrition and some concerns associated with aging, including the role that exercise can have on reducing the negative effects of this phenomenon. Some results are inconsis- tent between studies and more replication studies underlying sarcopenia are needed, with larger samples and with different life cycles, particularly in the type and level of physical activity throughout life. In future we believe that further progress in understanding the ge- netic etiology and the metabolic pathways will provide valuable information on important biological mechanisms underlying the muscle physiology. This will enable better recognition of individuals at higher risk and the ability to more adequately address this debilitating condition.Sarcopenia é caracterizada por uma diminuição generalizada e progressiva da força, massa e função muscular com o envelhecimento. Recentemente, a determinação genética tem sido associada com a massa muscular e força muscular em idosos. Estes dois fenótipos de risco são os mais comumente reconhecidos e estudados em relação à sarcopenia, com hereditariedade variando de 30 a 85% para a força muscular e 45-90% para a massa muscular. É bem conhecido que o desenvolvimento e manutenção da massa muscular na idade adulta reduz o risco de desenvolver sarcopenia e conduz a um envelhecimento saudável. Por isso, é importante identificar quais os fatores genéticos que interagem com o envelhecimento e, em particular, com a resposta músculo-esquelética ao exercício. Esta revisão destina-se a resumir os estudos mais importantes e representativos sobre a possível associação entre determinados polimorfismos genéticos e fenótipos musculares nas populações mais velhas. Os aspetos nutricionais serão discutidos, incluindo o papel que o exercício pode ter sobre a redução dos efeitos negativos deste fenômeno. Alguns resultados são inconsistentes e desta forma é necessária uma maior replicação subjacente à sarcopenia, com amostras maiores e em diferentes ciclos da vida, especial- mente no tipo e nível de atividade física. No futuro, acreditamos que mais progressos na compreensão da etiologia genética e as vias metabólicas vai fornecer informações valiosas sobre importantes mecanismos biológicos envolvidos na fisiologia muscular. Isto irá permitir um melhor reconhecimento dos indivíduos com maior risco e uma maior capacidade de enfrentar adequadamente essa condição debilitante

Alterações músculo-esqueléticas relacionadas com o envelhecimento: causas e consequências

O aumento da população idosa e a crescente procura de tratamentos mais adequados para aliviar a dor causada pelos fatores que caracterizam o envelhecimento, particularmente a instalação da sarcopenia, condição associada ao sedentarismo e em alguns casos a enfermidades como artrites e artrose, são responsáveis pelo desenvolvimento de dores articulares que impossibilitam a prática de exercício físico, despoletando outros riscos como a osteoporose e perda da estabilidade postural que em conjunto aumentam o risco de quedas, lesões e fraturas associadas (Powers & Howley, 1997). Porém, a sua origem deverá ser igualmente interpretada muitas vezes como consequência das crescentes limitações do foro ortopédico. A inatividade conduz a um desuso do sistema músculo-esquelético e naturalmente a uma hipo-estimulação do tecido muscular conduzindo à atrofia do mesmo com diminuição da sua função (Tavares, C. 2003). Um exemplo categórico é o caso da osteoartrose do joelho, uma patologia articular crónica degenerativa, frequente em adultos e idosos que interfere na mobilidade e autonomia. A osteoartrose é caracterizada pela presença de dor e limitação funcional, consequência da formação de osteófitos e/ou alteração na integridade da cartilagem articular, que conduzem a uma perda gradual da força, diminuição da mobilidade e instabilidade articular. Frequentemente assistimos nos indivíduos com esta patologia a uma diminuição gradual nos seus níveis de atividade física, já que a imobilização da articulação contribui para diminuir o processo inflamatório na mesma, diminuindo também a dor. No entanto, a imobilização da articulação com artrose vai potenciar: a atrofia, o encurtamento de músculos e tendões, o surgimento de contracturas, a perda de massa óssea, o aumento do risco de fratura, a redução da mobilidade articular e a degeneração da cartilagem (Gordon, N., 1992). Assim, a inatividade física torna-se contraproducente, sendo a prescrição de exercício físico adequado uma forma de combater o avanço progressivo da doença. O fortalecimento da musculatura peri articular é fundamental para a obtenção do equilíbrio da articulação, controlando o impacto do pé sobre o solo durante a marcha, lubrificando a articulação e reduzindo os movimentos anormais entre as superfícies articulares o que ajuda a diminuir a degeneração da articulação (Roddy, E., W. Zhang, and M. Doherty, 2005). A manutenção do equilíbrio é um aspeto determinante na funcionalidade e autonomia estando relacionado como o sistema visual, somatosensorial e vestibular, com a força dos membros inferiores, nomeadamente os grupos musculares flexores e extensores das articulações do joelho e tibiotársica, que tendem a diminuir com a idade. Além disso, as alterações degenerativas dos discos intervertebrais, somados à diminuição da flexibilidade e da força das estruturas musculares e das posturas incorretas frequentes, conduzem a desalinhamentos nas curvaturas da coluna que por sua vez contribuem para a deterioração do equilíbrio, não só estático, como também dinâmico, e consequentemente do padrão de marcha. Neste contexto, a realização de atividade física é fundamental na prevenção de quedas e de fraturas associadas, tendo sido demonstrado por vários estudos que a participação em programas de exercício e o treino de tarefas especificamente orientadas para o sistema sensorial e a manutenção da estabilidade postural reduzem significativamente o número de quedas quando comparado a grupos de controlo, tanto em homens como em mulheres (Izquierdo et al., 2005; 2004). Em suma, o treino da força com intensidade moderada a elevada pode ser efetuado com elevada tolerância por parte de adultos e idosos, com resultados bastante satisfatórios em termos de adaptação morfológica e funcional, assim como também em termos de propriedades elétricas e contrácteis.

Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease

Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions

Which dengue vaccine approach is the most promising, and should we be concerned about enhanced disease after vaccination?: The path to a dengue vaccine: Learning from human natural dengue infection studies and vaccine trials

Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in humanclinical trials. Initial results are mixed, with variable efficacy dependingonDENVserotype and previousDENVexposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. © 2018 Cold Spring Harbor Laboratory Press; All rights reserved

Conformational study and reassessment of the vibrational assignments for Norspermidine

The present study presents and discusses the conformational preferences of Norspermidine (NSpd). The effects of varying the dielectric constant on the conformational preferences are discussed, with a view to infer which conformation will correspond to the most stable in the pure condensed liquid phase. Within the same context, a set of NSpd-NH3 molecular adducts were simulated in order to determine the relevance of intermolecular hydrogen bonding on the overall stability and relative positioning of the respective vibrational frequencies. The calculations presently performed allowed a reassessment of the vibrational assignments for NSpd. A full assignment of the NSpd vibrational spectra is presented, with special emphasis being given to the vibrational modes that proved to be most affected by hydrogen bonding. The various inconsistencies of a prior study found in the literature were identified and rectified

Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding

We have studied the growth of Borrelia burgdorferi in nymphal ticks (Ixodes scapularis) feeding on mice using confocal fluorescence microscopy to follow the distribution of spirochetes. In starved nymphs, the bacteria were only detected in the midgut and each nymph had it metro of 496 spirochetes. Upon attachment of nymphs to the host, the bacteria grew with a doubling time close to 4 hr and reached a mean of 7,848 spirochetes per nymph 15 hr after attachment. During this initial period (36 hr) of rapid growth, the bacteria appeared to be restricted to the gut, but after 48 hr, the spirochetes had disseminated to the salivary glands in the majority t)f nymphs examined. Thus, a critical event that allows the spirochetes to disseminate and infect the salivary glands takes place 36-48 hr after attachment. A maximum number of 166,575 spirochetes per nymph was noted 72 hr after attachment. Soon after completion of feeding and detachment from the host (96 hr), the mean number of spirochetes decreased to 95,410 per nymph and the spirochetes appeared to be cleared from organs other than the midgut. Thus, dissemination of spirochetes within the vector appears to be a transient phenomenon. These results provide strong evidence in favor of a salivary route of disease transmission while also demonstrating the utility of confocal microscopy to study vector-pathogen interactions in general

Structural differences between dengue viruses circulating in humans and viruses used for vaccine research

Four dengue virus (DENV) serotypes are mosquito-borne flaviviruses of humans. The main mosquito vector of DENV, Aedes aegypti, is difficult to control because urbanization and other human activities create environments that strongly favor this species. Given the challenges of mosquito vector control and the absence of other effective countermeasures, DENVs are thriving and infect several hundred million individuals, living in tropical and subtropical regions of the world [1,2]. Highly effective vaccines have been developed against related flaviviruses such as yellow fever (YFV), Japanese encephalitis (JEV) and tick-borne encephalitis (TBE) viruses [3]. The development of DENV vaccines is more challenging because of the presence of four serotypes and the possibility of inadequate immunity enhancing the replication of DENVs and thus, increasing the risk of severe disease [3]. Three live attenuated tetravalent DENV vaccines are at different stages of testing in people. Most recently, the public health community and vaccine developers faced a major setback when the leading candidate, Dengvaxia, was discovered to have a safety signal in some children [4]. Furthermore, we recently discovered that dengue serotype 1 viruses (DENV1) widely used for laboratory research are structurally different from DENV1 viruses circulating in the plasma of those infected [5]. Here, we discuss our findings and the implications for DENV research and vaccines

Evaluación de la obtención de aceite de girasol a partir de extracción acuosa enzimática usando enzimas proteasa

The aim of this work was to maximize the enzymatic aqueous extraction (EAE) of sunflower seed oil using protease enzymes from the evaluation of various temperatures, pH and enzyme concentrations, using a Box-Behnken experimental design. The effect of a thermal pre-treatment of sunflower seeds on free oil yield (FOY) and oil quality was also determined. In the experimental range adopted, a lower temperature (40 °C) provided higher FOY values, as well as the intermediate pH (8.00) and maximum enzyme concentration (9% v/v). Thermal pre-treatment provided an increase in FOY in the initial extraction times (60 to 180 min) and decreased of the extraction time of 4 to 3 h to obtain the highest FOY value (~16%). The fatty acid composition of the oils obtained showed a predominance of oleic (~47.5%) and linoleic acids (~39.5%). The total phytosterol content in the samples was hardly affected by the heat pre-treatment of the seeds, while the fatty acid profile, tocopherol content and oxidative stability were not altered.El objetivo de este trabajo fue maximizar la extracción acuosa enzimática (EAE) de aceite de semillas de girasol utilizando la enzima proteasa a partir de la evaluación de las variables temperatura, pH y concentración de la enzima, utilizando un diseño experimental de Box-Behnken. Además, se determinó el efecto del pretratamiento térmico de las semillas de girasol sobre el rendimiento (RA) y la calidad del aceite. En el rango experimental adoptado, las temperaturas más bajas (40 °C) proporcionaron valores de RA más altos, así como el pH intermedio (8,00) y la concentración máxima de enzima (9% v/v). El pretratamiento térmico proporcionó un aumento del RA en los tiempos de extracción iniciales (60 a 180 min) y una disminución del tiempo de extracción de 4 a 3 h para obtener el valor de RA más alto (~ 16%). La composición en ácidos grasos de los aceites obtenidos mostró predominio de los ácidos oleico (~47,5%) y linoleico (~39,5%). El contenido total de fitosteroles en las muestras se vio poco afectado por el pretratamiento térmico de las semillas, mientras que el perfil de ácidos grasos, el contenido de tocoferoles y la estabilidad oxidativa no se vieron afectados