135 research outputs found
Alternative Exon Usage Selectively Determines Both Tissue Distribution and Subcellular Localization of the acyl-CoA Thioesterase 7 Gene Products.
Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues. In this study, we have identified five possible first exons in mouse Acot7 (Acot7a-e) and show that all five first exons are transcribed in a tissue specific manner. Taken together, these data show that the Acot7 gene is expressed as multiple isoforms in a tissue specific manner, and that expression in tissues other than brain and testis is likely to play important roles in fatty acid metabolism
Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice
Background: Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. Methods: Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. Results: Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/ cholesterol and lipid synthesis. Conclusions: The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms
Resistance to Fusarium sacchari associated with pokkah boeng in sugarcane genotypes in a semiarid environment in Brazil / ResistĂȘncia Ă Fusarium sacchari associada Ă podridĂŁo do topo em genĂłtipos de cana-de-açĂșcar em um ambiente semiĂĄrido do Brasil
A Pokkah boeng Ă© uma doença causada por Fusarium sacchari que, embora ainda emergente, tem despertado atenção devido a sintomatologia observada em diversas regiĂ”es canavieiras do Brasil. Este estudo teve como objetivo avaliar a resistĂȘncia de genĂłtipos de cana-de-açĂșcar Ă F. sacchari nas condiçÔes ambientais de temperatura e umidade relativa preponderantes na regiĂŁo canavieira do estado do PiauĂ, Brasil. Inicialmente foi conduzido um ensaio no perĂodo chuvoso da regiĂŁo usando 16 clones de cana-de-açĂșcar que foram inoculados com F. sacchari via suspensĂŁo de esporos. Os nĂveis de resistĂȘncia foram estabelecidos por scores (de 0-5) de uma escala diagramĂĄtica e posterior classificação mediante o Ăndice de severidade da doença (ISD). Posteriormente, quatro clones de cana-de-açĂșcar com os menores e quatro com os maiores ISD selecionados previamente no primeiro ensaio foram submetidos a um novo ensaio durante o perĂodo seco da regiĂŁo, utilizando-se a mesma metodologia do primeiro ensaio. Ficou demonstrado que a agressividade do fungo se torna mais expressiva em alguns genĂłtipos, em geral, quando as mĂ©dias de temperaturas estĂŁo em torno de 34 0C e umidade relativa do ar em torno de 75%. Assim, no perĂodo seco do ano, correspondente ao perĂodo de junho a novembro, a incidĂȘncia desta doença Ă© praticamente nula mesmo para os genĂłtipos mais suscetĂveis. Assim, nossos resultados demonstram que, apesar de haver inĂłculo do patĂłgeno presente na regiĂŁo, o desenvolvimento de F. Sacchari nĂŁo causa danos significativos Ă cana-de-açĂșcar em virtude das condiçÔes ambientais que limitam Ă doença
Peroxisome proliferator-induced acyl-CoA thioesterase from rat liver cytosol: molecular cloning and functional expression in Chinese hamster ovary cells
Risks of myeloid malignancies in patients with autoimmune conditions
Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13â486 myeloid malignancy patients (aged 67+ years) and 160â086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies
Increase of SERS Signal Upon Heating or Exposure to a High-Intensity Laser Field: Benzenethiol on an AgFON Substrate
The surface-enhanced Raman scattering (SERS) signal from an AgFON plasmonic
substrate, recoated with benzenethiol, was observed to increase by about 100%
upon heating for 3.5 min at 100C and 1.5 min at 125C. The signal intensity was
found to increase further by about 80% upon a 10 sec exposure to a
high-intensity (3.2 kW/cm^2) 785-nm cw laser, corresponding to 40 mW in a
40+/-5-um diameter spot. The observed increase in the SERS signal may be
understood by considering the presence of benzenethiol molecules in an
intermediate or 'precursor' state in addition to conventionally ordered
molecules forming a self-assembled monolayer. The increase in the SERS signal
arises from the conversion of the molecules in the precursor state to the
chemisorbed state due to thermal and photo-thermal effects.Comment: 9 pages, 4 figures; J. Phys. Chem. C, accepte
Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells
<p>Abstract</p> <p>Background</p> <p>Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated.</p> <p>Methods</p> <p>We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using Îł-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs.</p> <p>Results</p> <p>Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h.</p> <p>Conclusions</p> <p>These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.</p
Transcriptional role of cyclin D1 in development revealed by a âgenetic-proteomicâ screen
Author manuscript: 2010 September 22.Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers[superscript 1, 2]. The full repertoire of cyclinâD1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclinâD1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclinâD1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclinâD1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinasâan organ that critically requires cyclinâD1 function[superscript 3, 4]âcyclinâD1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclinâD1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclinâD1-null (Ccnd1-/-) retinas. Transduction of an activated allele of Notch1 into Ccnd1-/- retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclinâD1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclinâD1 has an in vivo transcriptional function in mouse development. Our approach, which we term âgeneticâproteomicâ, can be used to study the in vivo function of essentially any protein
Distinct Populations of Hepatic Stellate Cells in the Mouse Liver Have Different Capacities for Retinoid and Lipid Storage
Hepatic stellate cell (HSC) lipid droplets are specialized organelles for the storage of retinoid, accounting for 50â60% of all retinoid present in the body. When HSCs activate, retinyl ester levels progressively decrease and the lipid droplets are lost. The objective of this study was to determine if the HSC population in a healthy, uninjured liver demonstrates heterogeneity in its capacity for retinoid and lipid storage in lipid droplets. To this end, we utilized two methods of HSC isolation, which leverage distinct properties of these cells, including their vitamin A content and collagen expression. HSCs were isolated either from wild type (WT) mice in the C57BL/6 genetic background by flotation in a Nycodenz density gradient, followed by fluorescence activated cell sorting (FACS) based on vitamin A autofluorescence, or from collagen-green fluorescent protein (GFP) mice by FACS based on GFP expression from a GFP transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i) increased expression of typical markers of HSC activation; (ii) decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT); (iii) decreased triglyceride levels; (iv) increased expression of genes associated with lipid catabolism; and (v) an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1. Conclusion: Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be âprimedâ and ready for rapid response to acute liver injury
Trocas gasosas e fluorescĂȘncia da clorofila em plantas de berinjela sob lĂąminas de irrigação
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