In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS

Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring non-neuronal cells. In vivo imaging by two-photon laser-scanning microscopy was used to compare the role of microglia/macrophage-related neuroinflammation in the CNS and PNS using ALS-linked transgenic SOD1G93A mice. These mice contained labeled projection neurons and labeled microglia/macrophages. In the affected lateral spinal cord (in contrast to non-affected dorsal columns), different phases of microglia-mediated inflammation were observed: highly reactive microglial cells in preclinical stages (in 60-day-old mice the reaction to axonal transection was ∼180% of control) and morphologically transformed microglia that have lost their function of tissue surveillance and injury-directed response in clinical stages (reaction to axonal transection was lower than 50% of control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any substantial morphological reaction while preclinical degeneration of peripheral motor axons and neuromuscular junctions was observed. We present in vivo evidence for a different inflammatory activity of microglia and macrophages: an aberrant neuroinflammatory response of microglia in the CNS and an apparently mainly neurodegenerative process in the PNS

Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain Barrier Permeability and Hypervascularity in Alzheimer's Disease

Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the “Vascular hypothesis”, holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration

Analytical model with lateral force for conventional CMUT membranes under large deflection using Von Kármán equations

2016 IEEE International Ultrasonics Symposium, IUS 2016, France, 18-21 September 2016Capacitive Micromachined Ultrasonic Transducer (CMUT) is a new type of ultrasound wave generator and detector. Analytical method is intuitive to understand the mechanism and physical effects through modeling of CMUT. To optimize the design procedures of CMUT membrane undergoing large deflection, a new analytical model with the consideration of the lateral force using Von Kármán equations is proposed. This model is capable of calculating the membrane profile of the CMUT since it includes the effect of the lateral force. The calculated results match well with the simulated results and the maximum deflection error in the center of the CMUT is less than 1% of the simulation results. The lateral force increases with the deflection of the membrane and it can be found that with the introduction of the lateral force, the proposed model can accurately estimate the membrane large defection profile in both single and double-layer membrane cases. The capacitance of the CMUT can be derived when the deflection profile of the membrane is available.Department of Industrial and Systems Engineerin

Manutenção da qualidade de rosas cortadas cv. Vega em soluções conservantes Keeping quality of cut roses cv. Vega in holding solutions

A rosa é considerada uma das flores de corte mais tradicionais e requisitadas no mercado mundial. Entretanto, após o corte, essas flores tornam-se altamente perecíveis devido à elevada atividade metabólica que conduz aos processos de senescência. Assim, o experimento foi realizado para verificar o efeito do uso de soluções conservantes na fisiologia pós-colheita de rosas vermelhas cortadas cultivar Vega. Utilizou-se o delineamento inteiramente casualizado, em esquema fatorial composto por dois fatores: sete tratamentos pós-colheita e quatro datas de avaliação. As flores permaneceram nas seguintes soluções de manutenção: 1) Água destilada; 2) 8-hidroxiquinolina (200 mg L-1); 3) 8-hidroxiquinolina (200 mg L-1) + Sacarose (20 mg L-1); 4) Ácido cítrico (75 mg L-1); 5) Ácido cítrico (75 mg L-1) + Sacarose (20 mg L-1); 6) 6-benziladenina (60 mg L-1); 7) 6 benziladenina (60 mg L-1) + Sacarose (20 mg L-1). Foram realizadas análises qualitativas e fisiológicas ao longo do período de avaliação. O tratamento com 8-hidroxiquinolina e ácido cítrico revelaram-se mais promissores para manter a qualidade e prolongar a vida de vaso das flores, o que foi evidenciado pela menor perda de massa fresca, atividade respiratória e conteúdo relativo de água; melhor manutenção do conteúdo de carboidratos solúveis e redutores, antocianina e coloração.<br>The rose is considered one of the most traditional and required cut flowers in the world market. However, after cutting, these flowers become highly perishable, because the high metabolic activity leads to senescence processes. The experiment was accomplished to verify the effect of holding solutions on the postharvest physiology of cut red roses, cv. Vega. A randomized design in a factorial scheme composed by two factors was used: seven postharvest treatments and four evaluation dates. The flowers remained in the following holding solutions: 1) Distilled water; 2) 8-hydroxyquinoline citrate (200 mg L-1); 3) 8-hydroxyquinoline citrate (200 mg L-1) + Sucrose (20 mg L-1); 4) Citric acid (75 mg L-1); 5) Citric acid (75 mg L-1) + Sucrose (20 mg L-1); 6) 6-benzyladenine (60 mg L-1); 7) 6-benzyladenine (60 mg L-1) + Sucrose (20 mg L-1). Qualitative and physiologic analyses were carried out during the evaluation period. The treatment with 8-hydroxyquinoline citrate and citric acid were the most promising to keep the quality and extend the vase life of flowers content; better maintenance of soluble and reducing carbohydrates, anthocyanin and color