Genomic structure, promoter activity, and developmental expression of the mouse homologue of the Machado–Joseph disease (MJD) gene

Machado–Joseph disease (MJD) is a neurodegenerative disorder, caused by the expansion of the (CAG)n tract in the MJD gene. This encodes the protein ataxin-3, of unknown function. The mouse Mjd gene has a structure similar to that of its human counterpart and it also contains a TATA-less promoter. Its 5V flanking region contains conserved putative binding regions for transcription factors Sp1, USF, Arnt, Max, E47, and MyoD. Upon differentiation of P19 cells, the Mjd gene promoter is preferentially activated in endodermal and mesodermal derivatives, including cardiac and skeletal myocytes; and less so in neuronal precursors. Mouse ataxin-3 is ubiquitously expressed during embryonic development and in the adult, with strong expression in regions of the CNS affected in MJD. It is particularly abundant in all types of muscle and in ciliated epithelial cells, suggesting that it may be associated with the cytoskeleton and may have an important function in cell structure and/or motility.Fundação Luso-Americana para o Desenvolvimento - (Proc. 3.L./A.II/P.582/99Fundação para a Ciência e a Tecnologia (FCT) - (Project POCTI/MGI 33759/99), BD/9759/ 2003).Fundo Social Europeu (FSE) - Fundo Europeu de Desenvolvimento Regional (FEDER)

Phytochemicals with Added Value from Morella and Myrica Species

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. For instance, in Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases. A wide array of compounds isolated from different parts of Myrica and/or Morella species possess several biological activities, like anticancer, antidiabetic, anti-obesity, and cardio-/neuro-/hepatoprotective activities, both in vitro and in vivo, with myricanol, myricitrin, quercitrin, and betulin being the most promising. There are still many other compounds isolated from both genera whose biological activities have not been evaluated, which represents an excellent opportunity to discover new applications for those compounds and valorize Morella/Myrica species.This research was funded by FCT-Fundação para a Ciência e a Tecnologia, supporting G.P.R.'s grant (SFRH/BD/144446/2019) as well by FCT-Fundação para a Ciência e Tecnologia, the European Union, QREN, FEDER, and COMPETE, through funding the cE3c center (UIDB/00329/2020) and the LAQV-REQUIMTE (UIDB/50006/2020). Funded by RTI2018-094356-B-C21 Spanish MINECO project, co-funded by European Regional Development Fund (FEDER).info:eu-repo/semantics/publishedVersio

GC- and UHPLC-MS Profiles as a Tool to Valorize the Red Alga Asparagopsis armata

Asparagopsis armata Harvey is a red alga native from the southern hemisphere and then introduced in the Mediterranean Sea and the Atlantic Ocean, including the Azores Archipelago, where it is considered an invasive alga. Some studies show that the extracts exhibit antimicrobial and antifouling activities, and it is incorporated in some commercialized cosmetic products. (e.g., Ysaline®). However, knowledge of this species chemical composition is scarce. The GC-MS and UHPLC-MS profiles of both the nonpolar and polar extracts were established to contribute to this problem solution. According to the results, A. armata is rich in a great structural variety of halogenated lipophilic and aromatic compounds, some of them identified here for the first time. In the lipophilic extract, 25 compounds are identified, being the halogenated compounds and fatty acids, the two major compound families, corresponding to 54.8% and 35.7% of identified compounds (224 and 147 mg/100 g of dry algae, respectively). The 1,4-dibromobuten-1-ol and the palmitic acid are the two most abundant identified compounds (155 and 83.4 mg/100 g of dry algae, respectively). The polar extract demonstrated the richness of this species in brominated phenolics, from which the cinnamic acid derivatives are predominant. The results obtained herein open new perspectives for valuing the A. armata as a source of halogenated compounds and fatty acids, consequently improving its biotechnological and economic potential. Promoting this seaweed and the consequent increase in its demand will contribute to biodiversity conservation and ecosystem sustainability.This study was financed by ASPAZOR project (DRCT: ACORES-01-0145-FEDER-00060- ASPAZOR); Portuguese National Funds, through FCT-Fundação para a Ciência e a Tecnologia, and as applicable co-financed by the FEDER within the PT2020 Partnership Agreement by funding the LAQV-REQUIMTE (UIDB/50006/2020) and the cE3c centre (FCT Unit funding (Ref. UID/BIA/00329/2013, 20152018) and UID/BIA/00329/2019).info:eu-repo/semantics/publishedVersio

Instructional materials in a STSE perspective: an analisys of units produced by secondary chemistry teachers in continuant formation

Some research has shown that teachers present conceptions that indicate a vision of teaching focused on memorization and transmission of knowledge and do not consider an approach that regards to the STSE aspects. The aim of this study is to investigate the conceptions of contextualization present in instructional materials produced by a group of chemistry secondary teachers. The data were collected in a service course offered to teachers of São Paulo Metropolitan area. One of the strategies of the course was the production of instructional units based on STSE (Science, Technology, Society and Environment) orientations. The data analysis takes into account: presence of problematization, its development throughout the unit; the relations established between experiments or text and the proposed theme, and the nature of information presented in the texts (scientific, social, technological, environmental). Four context profiles were built to characterize the 13 units elaborated by the teachers. Four of the teachers’ units revealed simple contextualization view profiles, although six of them revealed more complex profiles, compatible with STSE orientation

Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products

Machado-Joseph disease (MJD) is a late-onset neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the ataxin-3 protein. We generated two transgenic mouse lineages expressing the expanded human ataxin-3 under the control of the CMV promoter: CMVMJD83 and CMVMJD94, carrying Q83 and Q94 stretches, respectively. Behavioral analysis revealed that the CMVMJD94 transgenic mice developed motor uncoordination, intergenerational instability of the CAG repeat and a tissue-specific increase in the somatic mosaicism of the repeat with aging. Histopathological analysis of MJD mice at early and late stages of the disease revealed neuronal atrophy and astrogliosis in several brain regions; however, we found no signs of microglial activation or neuroinflammatory response prior to the appearance of an overt phenotype. In our model, the appearance of MJD-like symptoms was also not associated with the presence of ataxin-3 cleavage products or intranuclear aggregates. We propose the transgenic CMVMJD94 mice as a useful model to study the early stages in the pathogenesis of MJD and to explore the molecular mechanisms involved in CAG repeat instability.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto for technical assistance. AS-F., M.C.C., S.S. and C.B. received FCT fellowships (SFRH/BD/15910/2005; SFRH/BPD/28560/2006; PTDC/SAU-GMG/64076/2006; SFRH/BPD/20987/2004). This research was funded by Fundacao para a Ciencia e Tecnologia through projects FEDER/FCT, POCI/SAU-MMO/60412/2004, PTDC/SAU-GMG/64076/2006; and Ataxia MJD Research Project

Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells

The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integrin subunit (ITGA5) and reduced activation of integrin signalling and is rescued by ITGA5 overexpression. Interestingly, silencing of ATXN3, overexpression of mutant versions of ATXN3 lacking catalytic activity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes. In vivo analysis showed that both Atxn3 knockout and MJD transgenic mice had decreased levels of ITGA5 in the brain. Furthermore, abnormal morphology and reduced branching were observed both in cultured neurons expressing shRNA for ATXN3 and in those obtained from MJD mice. Our results show that ATXN3 rescues ITGA5 from proteasomal degradation in neurons and that polyQ expansion causes a partial loss of this cellular function, resulting in reduced integrin signalling and neuronal cytoskeleton modifications, which may be contributing to neurodegeneration.National Institutes of Health (NIH) ‘(R01NS038712)Fundação para a Ciência e a Tecnologia (FCT) and COMPETE through the project ‘(PTDC/SAU-GMG/ 101572/2008)Fundação para a Ciência e a Tecnologia (FCT) - fellowships SFRH/BD/51059/2010, SFRH/BD/ 78388/2011 and SFRH/BPD/91562/201

Mineral Interaction in Biofortified Tomatoes (Lycopersicum esculentum L.) with Magnesium

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Prevenção à intoxicação por produtos químicos de uso doméstico

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