Exosomes regulate neurogenesis and circuit assembly.

Exosomes are thought to be released by all cells in the body and to be involved in intercellular communication. We tested whether neural exosomes can regulate the development of neural circuits. We show that exosome treatment increases proliferation in developing neural cultures and in vivo in dentate gyrus of P4 mouse brain. We compared the protein cargo and signaling bioactivity of exosomes released by hiPSC-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicates that control exosomes contain multiple functional signaling networks known to be important for neuronal circuit development. Treating MECP2-knockdown human primary neural cultures with control exosomes rescues deficits in neuronal proliferation, differentiation, synaptogenesis, and synchronized firing, whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capability. These data indicate that exosomes carry signaling information required to regulate neural circuit development

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA.

Macroautophagy (hereafter autophagy) is a key pathway in neurodegeneration. Despite protective actions, autophagy may contribute to neuron demise when dysregulated. Here we consider X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expanded androgen receptor (polyQ-AR). We found that polyQ-AR reduced long-term protein turnover and impaired autophagic flux in motor neuron-like cells. Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progression. We examined the transcriptional regulation of autophagy and observed a functionally significant physical interaction between transcription factor EB (TFEB) and AR. Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation. To evaluate physiological relevance, we reprogrammed patient fibroblasts to induced pluripotent stem cells and then to neuronal precursor cells (NPCs). We compared multiple SBMA NPC lines and documented the metabolic and autophagic flux defects that could be rescued by TFEB. Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy and promote SBMA pathogenesis

Definição da folha a ser amostrada para monitoramento de Mosca Branca (Bemisia tuberculata) na cultura da mandioca (Manihot esculenta Crantz).

A mandioca (Manihot esculenta Crantz) é uma cultura com crescente importância no mundo tropical, sendo a terceira fonte de calorias, atrás apenas do arroz e do milho, sendo utilizada na alimentação de cerca de 600 milhões de pessoas. No Brasil, aproximadamente 90% da produção da mandioca é obtida em propriedades de base familiar, sendo o país o terceiro produtor mundial, depois da Nigéria e da Tailândia, com uma produção de 26,52 milhões de toneladas de raízes, obtidas em uma área de cerca de 1,89 milhão de ha, o que corresponde a 12,37% da produção mundial e 10,20% da área, respectivamente (FAOSTAT, 2009). Essa é provavelmente a espécie vegetal mais disseminada pelo país, numa demonstração da profunda identificação entre essa cultura e o povo brasileiro. A cultura se caracteriza pela baixa necessidade de uso de insumos e agroquímicos, tem alta tolerância a períodos de seca, além de poder permanecer no solo até seu consumo, desempenhando papel importante na alimentação da população brasileira (CAMARGO, 2009). No entanto, por apresentar um longo ciclo vegetativo, está sujeita a uma grande diversidade de artrópodes que dela se alimentam (BELLOTTI et al., 1999). Dentro do complexo de insetos praga que atacam a cultura atualmente no Brasil, relata-se o crescimento da importância das espécies de mosca branca. Os gêneros mais importantes descritos atacando a cultura da mandioca no Brasil são Aleurothrixus aepim, Bemisia tuberculata, Trialeurodes variabilis e Bemisia tabaci biótipo B (OLIVEIRA & LIMA, 2006). No Centro-Sul do Brasil a espécie predominante é B. tuberculata, enquanto que no Nordeste destaca-se a espécie A. aepim (OLIVEIRA & LIMA, 2006). As moscas brancas causam danos diretos e indiretos, resultantes da sucção da seiva e transmissão de viroses, respectivamente (OLIVEIRA & LIMA, 2006). Para a supressão das populações desses insetos, apesar da existência de diversos inimigos naturais (BELLOTTI et al., 1999), tem-se predominado a utilização de inseticidas químicos, ainda que sem registros para essa cultura (AGROFIT, 2013) e ineficientes no controle do complexo de moscas brancas (MOREIRA et al., 2006). A utilização de variedades resistentes é outra estratégia de controle dessa praga, pois a mandioca é uma das poucas culturas onde se têm identificado níveis de resistência ao complexo de moscas brancas (CARABALI et al, 2010; OMONGO et al, 2012). Esta estratégia apresenta baixo custo e longa manutenção da população da praga abaixo do nível de dano econômico, além de reduzir perdas no rendimento, sendo uma importante ferramenta para ser incluída em um programa de manejo integrado de pragas (BELLOTTI et al., 1999). Para o estabelecimento de um eficiente programa de manejo integrado de pragas, além de utilizar várias estratégias de controle, é de suma importância um bom monitoramento da população da praga, visando à adoção de medidas de controle no momento ideal. Para a cultura da mandioca não se tem estabelecido um método de monitoramento preciso, eficiente e de baixo custo, principalmente para mosca branca. Observa-se que na cultura da mandioca os adultos de moscas brancas são encontrados principalmente nos ponteiros das plantas, onde se observa que o número de adultos presentes nas três primeiras folhas abertas, onde estes se alimentam e depositam seus ovos, é maior. Já as ninfas e 'pupas' são encontradas no terço apical e médio. Visando estabelecer um método de amostragem, que efetivamente seja representativo da população de mosca branca na cultura da mandioca, e considerando as características de localização dos adultos, se realizou este trabalho, cujo objetivo foi definir qual folha de mandioca deve ser amostrada durante o monitoramento de mosca branca em cultivos comerciais de mandioca, que expressem o nível populacional desta praga no cultivo

Comparison of 30 THz impulsive burst time development to microwaves, H-alpha, EUV, and GOES soft X-rays

The recent discovery of impulsive solar burst emission in the 30 THz band is raising new interpretation challenges. One event associated with a GOES M2 class flare has been observed simultaneously in microwaves, H-alpha, EUV, and soft X-ray bands. Although these new observations confirm some features found in the two prior known events, they exhibit time profile structure discrepancies between 30 THz, microwaves, and hard X-rays (as inferred from the Neupert effect). These results suggest a more complex relationship between 30 THz emission and radiation produced at other wavelength ranges. The multiple frequency emissions in the impulsive phase are likely to be produced at a common flaring site lower in the chromosphere. The 30 THz burst emission may be either part of a nonthermal radiation mechanism or due to the rapid thermal response to a beam of high-energy particles bombarding the dense solar atmosphere.Comment: accepted to Astronomy and Astrophysic

Myofibroma of the oral cavity. A rare spindle cell neoplasm

Myofibroma is an uncommon spindle cell neoplasm rarely found in oral cavity. Typically, this lesion is seen in neonates and infants with few cases reported in adults patients. In the oral cavity, myofibroma occurs within the submucosal or intramuscular tissue and has a predilection by the tongue, buccal mucosa and lips. Microscopically, a typical biphasic pattern can be observed. Misdiagnosis included benign and malignant spindle cell lesions of nerve tissue or smooth muscle origin, such as neurofibroma, leiomyoma and sarcomas. Thus, immunohistochemical staining is a useful tool to identify the nature of neoplastic cells and to reach an accurate diagnosis. An immunohistochemical panel consisting of antibodies to vimentin, SMA, HHF-35, S-100p and desmin must be achieved. In most cases, positivity for vimentin, SMA and HHF-25 can be observed. Our report describes a solitary myofibroma of the tongue of a 23-year-old man with emphasis in clinical, histopathological and immunohistochemical features of this lesion