135 research outputs found
Relationship between self-declared ethnicity, mitochondrial haplogroup and genomic ancestry in individuals from southeast of Brazil
Em populações onde há um alto grau de miscigenação, como no Brasil, o uso exclusivo de informações da etnia auto-declarada não é um bom método de classifi cação étnica. Neste trabalho, nós avaliamos a relação entre as etnias auto-declaradas com ancestralidade genômica e haplogrupos mitocondriais em 492 indivíduos do Sudeste Brasileiro. Haplogrupos mitocondriais foram obtidos pela análise das regiões hipervariáveis do DNA mitocondrial (mtDNA) e a ancestralidade genômica foi obtida utilizando 48 marcadores autossômicos informativos de ancestralidade (AIM). Dos 492 indivíduos, 74,6% se auto-declararam brancos, 13,8% pardos e 10,4% pretos. Em relação aos haplogrupos mitocondriais, 46,3% apresentaram mtDNA Africano e a maior contribuição de ancestralidade genômica foi Europeia (57,4%). Quando realizamos a distribuição do mtDNA e ancestralidade genômica de acordo com as etnias auto-declaradas, dos 367 indivíduos auto-declarados brancos, encontramos 37,6% com mtDNA Africano, sendo observado maior contribuição de ancestralidade Europeia (63,3%). Dos 68 indivíduos auto-declarados pardos, 25% apresentaram mtDNA Ameríndio e pouca diferen-ça na contribuição de ancestralidade Europeia e Africana. Dos 51 indivíduos auto-declarados pretos, 80,4% apresentaram mtDNA Africano e maior contribuição de ancestralidade Africana (55,6%). A população brasileira apresenta uma uniformidade de ancestralidade genômica Ameríndia, e apenas o uso de marcadores genéticos (autossômico e mitocondrial) foi capaz de capturar essa informação. Sugerimos que estudos epidemiológicos façam o uso associado destes métodos, pois poderiam fornecer informações complementares.In populations where there is a high degree of admixture, as in Brazil, the sole use of ethnicity self-declaration information is not a good method of ethnic classifi cation. We evaluate the relationship between self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from Southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of mitochondrial DNA (mtDNA) and genomic ancestry was obtained using 48 autosomal ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as white, 13.8% as Brown and 10.4% as Black. In relation of mtDNA haplogroups, 46.3% presented African mtDNA and the major genomic ancestry was European (57.4%). When we performed the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities, from 367 individuals self-declared white, 37.6% showed African mtDNA, and had a higher contribution of European ancestry (63.3%). The 68 individuals self-declared brown, 25% showed Amerindian mtDNA and few differences in the averages contribution of European and African ancestries. Those 51 subjects self-declared black, 80.4% had African mtDNA and the main contribution of African ancestry (55.6%). The Brazilian population had a very uniform degree of Amerindian genomic ancestry, and only by using genetic markers (autosomal and mitochondrial) we were able to capture this information. Epidemiological studies should use the association of these methods to provide complementary information
3 d(2) configuration in six-times-ionized argon, ArVII
The transition array 2p(6)3p3d-2p(6)3d(2) has been identified in the spectrum of magnesium-like Ar vii produced by electrical discharges in the vacuum-ultraviolet region. Twenty-five new transitions have been identified as combinations of levels of this transition array. From these transitions we have determined the levels of the 3d(2) configuration. It was also possible to determine the 2p(6)3p3d(1)D(2)(o) level that was missed in the early research with the Ar vii spectrum. Hartree-Fock calculations with relativistic corrections were used to predict energy levels and transitions. Isoelectronic comparisons along the Mg I sequence are used to support the experimental results. (C) 2001 Optical Society of America.18111718172
Widespread cell stress and mitochondrial dysfunction in early Alzheimer’s Disease
Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). We quantified the in vivo density of the endoplasmic reticulum stress marker, the sigma 1 receptor (S1R) using [11C]SA4503 PET, as well as that of mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and brain perfusion (CBF) measured with MRI arterial spin labelling. 8 AD patients were followed longitudinally to estimate rates of change with disease progression over 12-18 months. The AD patients showed widespread increases in S1R (≤ 27%) and regional decreases in MC1 (≥ -28%), SV2A (≥ -25%), brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 density (≥ -12%) and brain volumes (≥ -5%) were further reduced at follow up in brain regions consistent with the differences between AD patients and controls at baseline. Exploratory analyses showing associations of MC1, SV2A and S1R density with cognitive changes at baseline and longitudinally with AD, but not in controls, suggested a loss of metabolic functional reserve with disease. Our study thus provides novel in vivo evidence for widespread cellular stress and bioenergetic abnormalities in early AD and that they may be clinically meaningful
Conservation of geosites as a tool to protect geoheritage: the inventory of Ceará Central Domain, Borborema Province - NE/Brazil
The Ceará Central Domain, in the northern Borborema Province/NE Brazil, encompasses important geological records (geosites) which allow understanding a relevant period of the Earth’s evolution, mainly associated to Neoproterozoic Brazilian/Pan-African Cycle and West Gondwana amalgamation, besides Neoarchean to Ordovician records. The presented geoheritage inventory aims to characterise the geosites with scienti c relevance of Ceará Central Domain. By applying a method for large areas, the nal selection resulted in eight geological frameworks represented by 52 geosites documented in a single database. This is the rst step for a geoconservation strategy based on systematic inventories, statutory protection, geoethical behaviour and awareness about scienti c, educational and/or cultural relevance of geosites.We specially thank all experts that helped us with
this inventory: Afonso Almeida, Carlos E.G. de
Araújo, César Veríssimo, Christiano Magini, Clóvis
Vaz Parente, Felipe G. Costa, Irani C. Mattos,
Neivaldo de Castro, Otaciel de Melo, Sebástian G.
Chiozza, Ticiano Santos and Stefano Zincone. We
are also thankful to Kátia Mansur, Ricardo Fraga
Pereira and anonymous reviewers for their valuable
contributions. PM is grateful to Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior
(CAPES) for PhD mobility scholarship PDSE
Program/Process n 88881.132168/2016-01info:eu-repo/semantics/publishedVersio
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Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats
Rationale
The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour.
Objectives
The objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure.
Methods
Male Lister hooded rats were administered CBG (30–120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30–240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h.
Results
CBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120–240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased.
Conclusions
Here, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted
Increasing gene dosage greatly enhances recombinant expression of aquaporins in Pichia pastoris
<p>Abstract</p> <p>Background</p> <p>When performing functional and structural studies, large quantities of pure protein are desired. Most membrane proteins are however not abundantly expressed in their native tissues, which in general rules out purification from natural sources. Heterologous expression, especially of eukaryotic membrane proteins, has also proven to be challenging. The development of expression systems in insect cells and yeasts has resulted in an increase in successful overexpression of eukaryotic proteins. High yields of membrane protein from such hosts are however not guaranteed and several, to a large extent unexplored, factors may influence recombinant expression levels. In this report we have used four isoforms of aquaporins to systematically investigate parameters that may affect protein yield when overexpressing membrane proteins in the yeast <it>Pichia pastoris</it>.</p> <p>Results</p> <p>By comparing clones carrying a single gene copy, we show a remarkable variation in recombinant protein expression between isoforms and that the poor expression observed for one of the isoforms could only in part be explained by reduced transcript levels. Furthermore, we show that heterologous expression levels of all four aquaporin isoforms strongly respond to an increase in recombinant gene dosage, independent of the amount of protein expressed from a single gene copy. We also demonstrate that the increased expression does not appear to compromise the protein folding and the membrane localisation.</p> <p>Conclusions</p> <p>We report a convenient and robust method based on qPCR to determine recombinant gene dosage. The method is generic for all constructs based on the pPICZ vectors and offers an inexpensive, quick and reliable means of characterising recombinant <it>P. pastoris </it>clones. By using this method we show that: (1) heterologous expression of all aquaporins investigated respond strongly to an increase in recombinant gene dosage (2) expression from a single recombinant gene copy varies in an isoform dependent manner (3) the poor expression observed for AtSIP1;1 is mainly caused by posttranscriptional limitations. The protein folding and membrane localisation seems to be unaffected by increased expression levels. Thus a screen for elevated gene dosage can routinely be performed for identification of <it>P. pastoris </it>clones with high expression levels of aquaporins and other classes of membrane proteins.</p
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