RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury

IntroductionGlaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE–Aß axis plays a role in RGC loss in experimental glaucoma.MethodsRetinal ischemia was induced by an acute elevation of intraocular pressure in RAGE–/– and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.ResultsRetinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE–/– mice (36 ± 3% p < 0.0001 vs. 19 ± 2%, p = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE–/– mice, 7-days post-injection (55 ± 4% p = 0.008 vs. 24 ± 2%, p = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE–/– (36 ± 3% vs. 16 ± 6%).DiscussionRAGE–/– mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE–/–. A co-localization of RAGE and Aß, suggests that RAGE–Aß binding may contribute to RGC loss

Flutuação de esporos de Plasmopara vitícola em cultivo protegido de videira.

o uso da cobertura plástica (CP) no cultivo de videiras pode apresentar vantagens no ganho em qualidade das uvas, protegendo çle prejuizos causados por granizos e doenças fúngicas. O mildio da videira (P/asmopaf'8 vilico/a) é a' doença fúngica com maior importância no que diz respeito à incidência e gastos com aplicações de fungicidas. A modificação microclimática que a CP pode exercer sobre o vinhedo, sobretudo pela eliminação da água livre sobre folhas e cachos, contribui para a diminuição de incidência e severidade de doenças fúngicas de forma geral.Resumo

Mesenchymal/Stromal Gene Expression Signature Relates to Basal-Like Breast Cancers, Identifies Bone Metastasis and Predicts Resistance to Therapies

BACKGROUND: Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm. METHODOLOGY/PRINCIPAL FINDINGS: By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis

The suitability and acceptability of a co-designed prototype psychoeducational activity book for seven- to eleven-year-olds with ADHD

Young people with Attention Deficit Hyperactivity Disorder (ADHD) can benefit from psychoeducation interventions. Co-design of these interventions increases engagement and impact. However, there are very few age-appropriate co-designed psychoeducational resources for young people with ADHD. Therefore an activity book prototype (‘ADHD Hero Activity Book’) was co-designed to teach 7–11-year-olds with ADHD about their condition and how to manage it more effectively. This paper describes the initial evaluation of this prototype. Nine parents and eleven children took part across nine online workshops and one phone call. The suitability and acceptability of the activity book prototype was explored, and areas of improvement identified. Sketch notes were taken for respondent validity and engagement purposes. Thematic analysis identified six themes: (1) Visual information; (2) Topic interest and engagement; (3) Importance of relatable content; (4) Importance of activity book interaction and age-appropriate content; (5) Positive aspects of ADHD and (6) The activity book as a communication aid. Improvement suggestions were also provided. Results indicate the activity book is suitable, acceptable and can act as a communication aid between young people and families. Future research may consider the development of versions of the activity book for adolescents with ADHD and young people with Autism Spectrum Disorder

COMPARAÇÃO ENTRE OS PERFIS DE LIBERAÇÃO DE AZUL DE METILENO A PARTIR DE MICROPARTÍCULAS DE ALGINATO-QUITOSANA EM PH ÁCIDO

A utilização de alginato de sódio como biopolímero formador de micropartículas vêm sendo largamente estudada e investigada para obtenção de formas farmacêuticas de liberação controlada. Neste trabalho avaliou-se o perfil de liberação do azul de metileno de micropartículas deste polímero, preparadas por reticulação iônica com quitosana, com a presença ou não de sódio, em tampão ácido clorídrico pH 1,5, considerando o azul de metileno como modelo de princípio ativo de baixo peso molecular

AVALIAÇÃO DA INFLUÊNCIA DA VARIABILIDADE DE ÓLEOS NO MICROENCAPSULAMENTO DE FÁRMACOS HIDROFÍLICOS DE BAIXO PESO MOLECULAR POR EMULSIFICAÇÃO A/O

A obtenção de micropartículas por técnicas de emulsificação assumiu grande relevância para o microencapsulamento de fármacos hidrofílicos. O trabalho avalia o uso de diferentes óleos vegetais para o processo de obtenção de micropartículas por emulsificação a/o e observa sua influência no encapsulamento de fármacos de baixo peso molecular

Inside the eco-home: using video to understand the implications of innovative housing

As a method of qualitative research, video offers a means of looking into the world of a respondent and a means of stimulating a dialogue, both with the respondent and others. Video requires, however, the application of additional ethical procedures and may also increase refusal rates, if it is publicly disseminated. Applied to the home, the use of video reveals both practice and identity. Video records practice, showing how the spaces within a home are used at a particular time. For this reason, video is well adapted to understanding the implications of living in a home with an innovative design and technology, with all the complexities that this commonly involves. Equally, video communicates the appearance of the home and of its occupants to whoever is watching. Video is, therefore, intimately connected to identity and the home as a place