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21.
Inhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA-snRNA-interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U1i results in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. We have now used these techniques to inhibit gene expression in mice. We show that U1ins can induce strong inhibition of the expression of target genes in vivo. Furthermore, combining U1i and RNAi results in synergistic inhibitions also in mice. This is shown for the inhibition of hepatitis B virus (HBV) sequences or endogenous Notch1. Surprisingly, inhibition obtained by combining a U1in and a RNAi mediator is higher than that obtained by combining two U1ins or two RNAi mediators. Our results suggest that RNAi and U1i cooperate by unknown mechanisms to result in synergistic inhibitions. Analysis of toxicity and specificity indicates that expression of U1i inhibitors is safe. Therefore, we believe that the combination of RNAi and U1i will be a good option to block damaging endogenous genes, HBV and other infectious agents in vivo. 相似文献
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We examined vegetation structure and woody species diversity in relation to 14 environmental and anthropogenic factors in
ten tropical dry forest (TDF) fragments in central Veracruz, Mexico. The basal area of the canopy (30.2 ± 2.11 m2/ha) and understory (1.96 ± 0.12 m2/ha) trees was similar, but density (1,014 ± 104 and 2,532 ± 227 individuals/ha, respectively) differed among sites. We recorded
98 canopy, 77 understory, and 60 seedling species. Richness was 24–45 species per site, Fisher’s alpha and Shannon’s indices
increased with site altitude. Chao Jaccard indices revealed high species turnover, and a consistently higher similarity within
the sites at the lowest and within the highest elevation sites. Ordination identified altitude, aspect, slope, water proximity,
cattle and trails as significant explanatory variables of species patterns, and showed that sites at lower elevations were
clearly separated from the other sites. Environmental heterogeneity alone did not control species diversity distribution,
but species were affected by environmental filters at different stages in their life cycle, e.g., water proximity was significant
for saplings and seedlings but not for adults. Anthropogenic disturbances act synergistically, e.g., trails played a key role
in determining structure and tree diversity patterns. An important finding is that human disturbance diminishes species diversity
in this TDF, but sites at lower elevations were more disturbed and less diverse, therefore we need to study how environmental
factors would act if there were no anthropogenic disturbance. 相似文献
23.
Santora VJ Covel JA Hayashi R Hofilena BJ Ibarra JB Pulley MD Weinhouse MI Semple G Ren A Pereira G Edwards JE Suarez M Frazer J Thomsen W Hauser E Lorea J Grottick AJ 《Bioorganic & medicinal chemistry letters》2008,18(14):4133-4136
A new series of H3 antagonists derived from the natural product Conessine are presented. Several compounds from these new series retain the potency and selectivity of earlier diamine based analogs while exhibiting improved PK characteristics. One compound (3u) demonstrated functional antagonism of the H3 receptor in an in vivo pharmacological model. 相似文献
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Gabriela Lorea Godoi Lisiane de Oliveira Porciúncula Janaína Fagundes Schulz Fernanda Neutzling Kaufmann João Batista da Rocha Diogo Onofre Gomes de Souza Gabriele Ghisleni Hiram Larangeira de Almeida Jr. 《Neurochemical research》2013,38(11):2359-2363
Neuropathological hallmarks of Alzheimer’s disease (AD) include amyloid plaque formation, neurofibrillary tangles, neuronal and synaptic loss. This study aims to identify the neuroprotective effects of the selenium compounds on the neurotoxicity of amyloid β(1–42) in primary cultures of murine hippocampal neurons. Samples were subjected to immunocytochemistry and western blotting techniques to determine the role of treatments on neuronal viability and synaptic protein SNAP-25. We observed a reduced cell viability amyloid β-peptide (1–42)-induced. When cells were co-treated with amyloid β-peptide (1–42) and selenium compounds, we verified a strong increase in relative cell viability and in the level of synaptic marker synaptosomal-associated protein SNAP-25 induced by selenium compounds. 相似文献
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Vernica Can Alfonso Gmez-Iturriaga Francisco Casquero Dirk Rades Arturo Navarro Olga del Hoyo Virginia Morillo Patricia Willisch Jos Luis Lpez-Guerra Ana Illescas-Vacas Raquel Ciervide Lorea Martinez-Indart Jon Cacicedo 《Reports of Practical Oncology and Radiotherapy》2022,27(3):428
BackgroundThe aim of the study was to analyze the impact of palliative radiotherapy on quality of life (QoL) in patients with symptomatic bone metastases.Materials and methodsWe present the results from a prospective multicentric study including 128 patients who provided pre- and post-radiotherapy (one month after treatment) brief pain inventory (BPI) assessments. Worst pain was recorded using the BPI (range: 0–10). Pain response was described according to the International Bone Metastases Consensus on palliative radiation. Regarding QoL, for each pre- and post-radiation BPI-questionnaire, scores from the interference domains were summed and averaged to obtain an overall interference score.ResultsThere was a significant correlation between radiation treatment response and improvement in all functional interference domains except sleeping. Patients > 75 years old presented a significantly higher improvement in general activity, mood and relationships with others compared to patients ≤ 75 years old. Patients presenting a baseline pain score ≥ 8 showed a higher improvement in the general activity item (p = 0.049). There was no statistically significant association between pretreatment ECOG, chemotherapy, primary tumor location and radiation schedule with any of the functional interference items.ConclusionsPatients who report pain relief after palliative radiotherapy also present a better quality of life including physical and psychosocial aspects. 相似文献
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The effect of a well-defined mild shear stress on hybridoma cell viability (HB-8852) in a serum-free culture medium has been
analysed, and the role as shear protector of different concentrations of fetal bovine serum have been studied. Samples harvested
from cultures in their late exponential growth phase, were subjected in a rheometer to a constant shear stress of 0.41 ± 0.02 Pa,
and the evolution of viable and total cell concentrations was determined and compared with static controls. A simple segregated
kinetic model for the viable and dead cells was used to know the effect of serum concentration on the specific cell growth
and death rate of the cells. 相似文献