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991.
Sandra Regina Lepri Leonardo Campos Zanelatto Patrícia Benites Gonçalves da Silva Daniele Sartori Lucia Regina Ribeiro Mario Sergio Mantovani 《Human cell》2014,27(2):78-84
Soybean isoflavonoids have received significant attention due to their potential anticarcinogenic and antiproliferative effects and possible role in many signal transduction pathways. However, their mechanisms of action and their molecular targets remain to be further elucidated. In this paper, we demonstrated that two soybean isoflavones (genistein and daidzein) reduced the proliferation of the human colon adenocarcinoma grade II cell line (HT-29) at concentrations of 25 and 50–100 μM, respectively. We then investigated the effects of genistein and daidzein by RT-PCR on molecules that involved in tumor development and progression by their regulation of cell proliferation. At a concentration of 50 μM genistein, there was suppressed expression of β-catenin (CTNNBIP1). Neither genistein nor daidzein affected APC (adenomatous polyposis coli) or survivin (BIRC5) expression when cells were treated with concentrations of 10 or 50 μM. These data suggest that the down-regulation of β-catenin by genistein may constitute an important determinant of the suppression of HT-29 cell growth and may be exploited for the prevention and treatment of colon cancer. 相似文献
992.
Leandro Fernandes Andrade Gleika Larisse Oliveira Dorasio de Souza Silvia Nietsche Adelica Aparecida Xavier Marcia Regina Costa Acleide Maria Santos Cardoso Marlon Cristian Toledo Pereira Débora Francine Gomes Silva Pereira 《Journal of microbiology (Seoul, Korea)》2014,52(1):27-34
A total of 40 endophytic bacterial isolates obtained from banana tree roots were characterized for their biotechnological potential for promoting banana tree growth. All isolates had at least one positive feature. Twenty isolates were likely diazotrophs and formed pellicles in nitrogen-free culture medium, and 67% of these isolates belonged to the genus Bacillus sp. The isolates EB-04, EB-169, EB-64, and EB-144 had N fixation abilities as measured by the Kjeldahl method and by an acetylene reduction activity assay. Among the 40 isolates, 37.5% were capable of solubilizing inorganic phosphate and the isolates EB-47 and EB-64 showed the highest solubilization capacity. The isolate EB-53 (Lysinibacillus sp.) had a high solubilization index, whereas 73% of the isolates had low solubilization indices. The synthesis of indole-3-acetic acid (IAA) in the presence of L-tryptophan was detected in 40% of the isolates. The isolate EB-40 (Bacillus sp.) produced the highest amount of IAA (47.88 μg/ml) in medium supplemented with L-tryptophan and was able to synthesize IAA in the absence of L-tryptophan. The isolates EB-126 (Bacillus subtilis) and EB-47 (Bacillus sp.) were able to simultaneously fix nitrogen, solubilize phosphate and produce IAA in vitro. The results of this study demonstrated that the isolates analyzed here had diverse abilities and all have the potential to be used as growth-promoting microbial inoculants for banana trees. 相似文献
993.
Vitor G.L. Dantas Karina Lezirovitz Guilherme L. Yamamoto Carolina Fischinger Moura de Souza Simone Gomes Ferreira Regina C. Mingroni-Netto 《Genetics and molecular biology》2014,37(4):616-621
We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technology yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement using microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hearing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 variants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal dominant hereditary hearing loss and corresponds to DFNA17. The mutation identified in our study is the same described in the prior report. Thus, although linkage studies suggested a candidate gene in chromosome 14, we concluded that the mutation in chromosome 22 better explains the hearing loss phenotype in the Brazilian family. 相似文献
994.
Amanda Alves de Paiva Rolla Josirley de Fátima Corrêa Carvalho Renata Fuganti-Pagliarini Cibelle Engels Alexandre do Rio Silvana Regina Rockenbach Marin Maria Cristina Neves de Oliveira Magda A. Beneventi Francismar Corrêa Marcelino-Guimarães José Renato Bouças Farias Norman Neumaier Kazuo Nakashima Kazuko Yamaguchi-Shinozaki Alexandre Lima Nepomuceno 《Transgenic research》2014,23(1):75-87
995.
Nurije Mustafi Alexander Grünberger Regina Mahr Stefan Helfrich Katharina N?h Bastian Blombach Dietrich Kohlheyer Julia Frunzke 《PloS one》2014,9(1)
The majority of biotechnologically relevant metabolites do not impart a conspicuous phenotype to the producing cell. Consequently, the analysis of microbial metabolite production is still dominated by bulk techniques, which may obscure significant variation at the single-cell level. In this study, we have applied the recently developed Lrp-biosensor for monitoring of amino acid production in single cells of gradually engineered L-valine producing Corynebacterium glutamicum strains based on the pyruvate dehydrogenase complex-deficient (PDHC) strain C. glutamicum ΔaceE. Online monitoring of the sensor output (eYFP fluorescence) during batch cultivation proved the sensor''s suitability for visualizing different production levels. In the following, we conducted live cell imaging studies on C. glutamicum sensor strains using microfluidic chip devices. As expected, the sensor output was higher in microcolonies of high-yield producers in comparison to the basic strain C. glutamicum ΔaceE. Microfluidic cultivation in minimal medium revealed a typical Gaussian distribution of single cell fluorescence during the production phase. Remarkably, low amounts of complex nutrients completely changed the observed phenotypic pattern of all strains, resulting in a phenotypic split of the population. Whereas some cells stopped growing and initiated L-valine production, others continued to grow or showed a delayed transition to production. Depending on the cultivation conditions, a considerable fraction of non-fluorescent cells was observed, suggesting a loss of metabolic activity. These studies demonstrate that genetically encoded biosensors are a valuable tool for monitoring single cell productivity and to study the phenotypic pattern of microbial production strains. 相似文献
996.
Regina Boecker Nathalie E. Holz Arlette F. Buchmann Dorothea Blomeyer Michael M. Plichta Isabella Wolf Sarah Baumeister Andreas Meyer-Lindenberg Tobias Banaschewski Daniel Brandeis Manfred Laucht 《PloS one》2014,9(8)
Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring''s age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. 相似文献
997.
Regina Cencic Hisashi Miura Abba Malina Francis Robert Sylvain Ethier T. Martin Schmeing Josée Dostie Jerry Pelletier 《PloS one》2014,9(10)
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the in vivo target specificity of Cas9 is poorly understood and most studies rely on in silico predictions to define the potential off-target editing spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate the genome-wide binding panorama of catalytically inactive Cas9 directed by two different single guide (sg) RNAs targeting the Trp53 locus. Cas9:sgRNA complexes are able to load onto multiple sites with short seed regions adjacent to 5′NGG3′ protospacer adjacent motifs (PAM). Yet among 43 ChIP-seq sites harboring seed regions analyzed for mutational status, we find editing only at the intended on-target locus and one off-target site. In vitro analysis of target site recognition revealed that interactions between the 5′ end of the guide and PAM-distal target sequences are necessary to efficiently engage Cas9 nucleolytic activity, providing an explanation for why off-target editing is significantly lower than expected from ChIP-seq data. 相似文献
998.
Ricardo Arraes de Alencar Ximenes Celina Maria Turchi Martelli Marcos Amaku Ana Marli C. Sartori Patricia Coelho de Soárez Hillegonda Maria Dutilh Novaes Leila Maria Moreira Beltr?o Pereira Regina Célia Moreira Gerusa Maria Figueiredo Raymundo Soares de Azevedo for the Hepatitis Study Group 《PloS one》2014,9(5)
Background
This study aimed to identify the transmission pattern of hepatitis A (HA) infection based on a primary dataset from the Brazilian National Hepatitis Survey in a pre-vaccination context. The national survey conducted in urban areas disclosed two epidemiological scenarios with low and intermediate HA endemicity.Methods
A catalytic model of HA transmission was built based on a national seroprevalence survey (2005 to 2009). The seroprevalence data from 7,062 individuals aged 5–69 years from all the Brazilian macro-regions were included. We built up three models: fully homogeneous mixing model, with constant contact pattern; the highly assortative model and the highly assortative model with the additional component accounting for contacts with infected food/water. Curves of prevalence, force of infection (FOI) and the number of new infections with 99% confidence intervals (CIs) were compared between the intermediate (North, Northeast, Midwest and Federal District) and low (South and Southeast) endemicity areas. A contour plot was also constructed.Results
The anti- HAV IgG seroprevalence was 68.8% (95% CI, 64.8%–72.5%) and 33.7% (95% CI, 32.4%–35.1%) for the intermediate and low endemicity areas, respectively, according to the field data analysis. The models showed that a higher force of infection was identified in the 10- to 19-year-old age cohort (∼9,000 infected individuals per year per 100,000 susceptible persons) in the intermediate endemicity area, whereas a higher force of infection occurred in the 15- to 29-year-old age cohort (∼6,000 infected individuals per year per 100,000 susceptible persons) for the other macro-regions.Conclusion
Our findings support the shift of Brazil toward intermediate and low endemicity levels with the shift of the risk of infection to older age groups. These estimates of HA force of infection stratified by age and endemicity levels are useful information to characterize the pre-vaccination scenario in Brazil. 相似文献999.
Cecilia Mannironi Marco Proietto Francesca Bufalieri Enrico Cundari Angela Alagia Svetlana Danovska Teresa Rinaldi Valeria Famiglini Antonio Coluccia Giuseppe La Regina Romano Silvestri Rodolfo Negri 《PloS one》2014,9(1)
Background
Histone demethylases (HDMs) have a prominent role in epigenetic regulation and are emerging as potential therapeutic cancer targets. The search for small molecules able to inhibit HDMs in vivo is very active but at the present few compounds were found to be specific for defined classes of these enzymes.Methodology/Principal Findings
In order to discover inhibitors specific for H3K4 histone demethylation we set up a screening system which tests the effects of candidate small molecule inhibitors on a S.cerevisiae strain which requires Jhd2 demethylase activity to efficiently grow in the presence of rapamycin. In order to validate the system we screened a library of 45 structurally different compounds designed as competitive inhibitors of α -ketoglutarate (α-KG) cofactor of the enzyme, and found that one of them inhibited Jhd2 activity in vitro and in vivo. The same compound effectively inhibits human Jumonji AT-Rich Interactive Domain (JARID) 1B and 1D in vitro and increases H3K4 tri-methylation in HeLa cell nuclear extracts (NEs). When added in vivo to HeLa cells, the compound leads to an increase of tri-methyl-H3K4 (H3K4me3) but does not affect H3K9 tri-methylation. We describe the cytostatic and toxic effects of the compound on HeLa cells at concentrations compatible with its inhibitory activity.Conclusions/Significance
Our screening system is proved to be very useful in testing putative H3K4-specific HDM inhibitors for the capacity of acting in vivo without significantly altering the activity of other important 2-oxoglutarate oxygenases. 相似文献1000.
Astrid Liedert Viktoria R?ntgen Thorsten Schinke Peggy Benisch Regina Ebert Franz Jakob Ludger Klein-Hitpass Jochen K. Lennerz Michael Amling Anita Ignatius 《PloS one》2014,9(7)
The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5−/−) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5−/− mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5−/− mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis. 相似文献