Curvas de dose-resposta para avaliação do controle de fluxos de emergência de plantas daninhas pelo herbicida imazapic

O objetivo deste trabalho foi avaliar o controle de dois fluxos de emergência das plantas daninhas capim-marmelada (Brachiaria plantaginea) e capim-colchão (Digitaria horizontalis) pelo herbicida imazapic, aplicado em condição de pré-emergência, por meio de curvas de dose-resposta. O delineamento experimental foi o de blocos ao acaso, com quatro repetições; cada parcela constou de um vaso de 3 L de capacidade, preenchido com solo argiloso, acrescido de sementes de capim-marmelada e capim-colchão. Sendo D a dose recomendada do imazapic (140 g ha-1), os tratamentos foram: 4D, 2D, D, 1/2D, 1/4D, 1/8D, 1/16D e ausência do herbicida. Foram realizadas avaliações visuais de controle aos 30 e 60 dias após a infestação (DAI) e de massa seca aos 60 DAI. Após a colheita da biomassa resultante do primeiro fluxo de emergência presente nas parcelas, os vasos foram novamente semeados com as plantas daninhas e foram realizadas novas avaliações de controle aos 30 e 60 dias após reinfestação (DAR) e de massa seca aos 60 DAR. A partir dos resultados obtidos, pode-se afirmar que: o imazapic inibiu o desenvolvimento de ambas as plantas daninhas, alcançando resultados superiores a 80% de controle em todas as avaliações, para a dose recomendada, nos dois fluxos de emergência; a eficácia no controle de capim-colchão foi ligeiramente superior à do controle do capim-marmelada; e o herbicida imazapic apresentou-se como uma opção interessante para manejo dessas plantas daninhas.

Excessive functions, Appell polynomials and optimal stopping

The main topic of the thesis is optimal stopping. This is treated in two research articles. In the first article we introduce a new approach to optimal stopping of general strong Markov processes. The approach is based on the representation of excessive functions as expected suprema. We present a variety of examples, in particular, the Novikov-Shiryaev problem for Lévy processes. In the second article on optimal stopping we focus on differentiability of excessive functions of diffusions and apply these results to study the validity of the principle of smooth fit. As an example we discuss optimal stopping of sticky Brownian motion. The third research article offers a survey like discussion on Appell polynomials. The crucial role of Appell polynomials in optimal stopping of Lévy processes was noticed by Novikov and Shiryaev. They described the optimal rule in a large class of problems via these polynomials. We exploit the probabilistic approach to Appell polynomials and show that many classical results are obtained with ease in this framework. In the fourth article we derive a new relationship between the generalized Bernoulli polynomials and the generalized Euler polynomials.

Spectroscopic Studies of III-V Semiconductor Materials for Improved Devices

Defects in semiconductor crystals and at their interfaces usually impair the properties and the performance of devices. These defects include, for example, vacancies (i.e., missing crystal atoms), interstitials (i.e., extra atoms between the host crystal sites), and impurities such as oxygen atoms. The defects can decrease (i) the rate of the radiative electron transition from the conduction band to the valence band, (ii) the amount of charge carriers, and (iii) the mobility of the electrons in the conduction band. It is a common situation that the presence of crystal defects can be readily concluded as a decrease in the luminescence intensity or in the current flow for example. However, the identification of the harmful defects is not straightforward at all because it is challenging to characterize local defects with atomic resolution and identification. Such atomic-scale knowledge is however essential to find methods for reducing the amount of defects in energy-efficient semiconductor devices. The defects formed in thin interface layers of semiconductors are particularly difficult to characterize due to their buried and amorphous structures. Characterization methods which are sensitive to defects often require well-defined samples with long range order. Photoelectron spectroscopy (PES) combined with photoluminescence (PL) or electrical measurements is a potential approach to elucidate the structure and defects of the interface. It is essential to combine the PES with complementary measurements of similar samples to relate the PES changes to changes in the interface defect density. Understanding of the nature of defects related to III-V materials is relevant to developing for example field-effect transistors which include a III-V channel, but research is still far from complete. In this thesis, PES measurements are utilized in studies of various III-V compound semiconductor materials. PES is combined with photoluminescence measurements to study the SiO2/GaAs, SiNx/GaAs and BaO/GaAs interfaces. Also the formation of novel materials InN and photoluminescent GaAs nanoparticles are studied. Finally, the formation of Ga interstitial defects in GaAsN is elucidated by combining calculational results with PES measurements.

Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression

Curcumin, a major yellow pigment and active component of turmeric, has multiple anti-cancer properties. However, its molecular targets and mechanisms of action on human colon adenocarcinoma cells are unknown. In the present study, we examined the effects of curcumin on the proliferation of human colon adenocarcinoma HT-29 cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method and confirmed the curcumin-induced apoptosis by morphology and DNA ladder formation. At the same time, p53, phospho-p53 (Ser15), and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, pro-caspase-3, and pro-caspase-9 were determined by Western blot analysis. The colon adenocarcinoma cells were treated with curcumin (0-75 µM) for 0-24 h. We observed that p53 was highly expressed in HT-29 cells and curcumin could up-regulate the serine phosphorylation of p53 in a time- and concentration-dependent manner. An increase in expression of the pro-apoptotic factor Bax and a decrease in expression of the anti-apoptotic factor Bcl-2 were also observed in a time-dependent manner after exposure of 50 µM curcumin, while the expression of the anti-apoptotic factor Bcl-xL was unchanged. Curcumin could also down-regulate the expression of pro-caspase-3 and pro-caspase-9 in a time-dependent manner. These data suggest a possible underlying molecular mechanism whereby curcumin could induce the apoptosis signaling pathway in human HT-29 colon adenocarcinoma cells by p53 activation and by the regulation of apoptosis-related proteins. This property of curcumin suggests that it could have a possible therapeutic potential in colon adenocarcinoma patients.

Therapeutic effects of Sophora moorcroftiana alkaloids in combination with albendazole in mice experimentally infected with protoscolices of Echinococcus granulosus

The objective of the present study was to determine if the combination of alkaloids from Sophora moorcroftiana seeds and albendazole might be effective in the treatment of experimental echinococcosisin female NIH mice (6 weeks old and weighing 18-20 g, N = 8 in each group) infected withprotoscolices of Echinococcus granulosus. Viable protoscolices (N = 6 x 103) were cultured in vitro in 1640 medium and mortality was calculated daily. To determine the in vivo efficacy, mice were inoculated intraperitoneally with viable protoscolices and then treated once daily by gavage for three months with the alkaloids (50 mg kg-1 day-1) and albendazole (50 mg kg-1 day-1), separately and in combination (both alkaloids at 25 mg kg-1 day-1 and albendazole at 25 mg kg-1 day-1). Next, the hydatid cysts collected from the peritoneal cavity of the animals were weighed and serum IL-4, IL-2, and IgE levels were analyzed. Administration of alkaloids to cultured protoscolices showed significant dose- and time-dependent killing effects. The weight of hydatid cysts was significantly decreased upon treatment with each drug (P < 0.01), but the decrease was more prominent and the rate of hydatid cyst growth inhibition was much higher (76.1%) in the group receiving the combined treatments (18.3 ± 4.6 mg). IL-4 and total IgE were decreased (939 ± 447 pg/mL and 2.03 ± 0.42 IU/mL, respectively) in serum from mice treated with alkaloids and albendazole compared with the untreated control (1481 ± 619 pg/mL and 3.31 ± 0.37 IU/mL; P < 0.01). These results indicate that S. moorcroftiana alkaloids have protoscolicidal effects and the combination of alkaloids and albendazole has significant additive effects.

Chi-square analysis of the reduction of ATP levels in L-02 hepatocytes by hexavalent chromium

This study explored the reduction of adenosine triphosphate (ATP) levels in L-02 hepatocytes by hexavalent chromium (Cr(VI)) using chi-square analysis. Cells were treated with 2, 4, 8, 16, or 32 μM Cr(VI) for 12, 24, or 36 h. Methyl thiazolyl tetrazolium (MTT) experiments and measurements of intracellular ATP levels were performed by spectrophotometry or bioluminescence assays following Cr(VI) treatment. The chi-square test was used to determine the difference between cell survival rate and ATP levels. For the chi-square analysis, the results of the MTT or ATP experiments were transformed into a relative ratio with respect to the control (%). The relative ATP levels increased at 12 h, decreased at 24 h, and increased slightly again at 36 h following 4, 8, 16, 32 μM Cr(VI) treatment, corresponding to a "V-shaped" curve. Furthermore, the results of the chi-square analysis demonstrated a significant difference of the ATP level in the 32-μM Cr(VI) group (P < 0.05). The results suggest that the chi-square test can be applied to analyze the interference effects of Cr(VI) on ATP levels in L-02 hepatocytes. The decreased ATP levels at 24 h indicated disruption of mitochondrial energy metabolism and the slight increase of ATP levels at 36 h indicated partial recovery of mitochondrial function or activated glycolysis in L-02 hepatocytes.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

The efficacy of moxifloxacin-based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of randomized clinical trials

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitroand in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pyloritreatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients

Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situimmune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.

Single nucleotide polymorphisms predisposing to asthma in children of Mauritian Indian and Chinese Han ethnicity

Our objective was to investigate the distributions of six single nucleotide polymorphisms (SNPs) MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA I75V,IL4 C-590T, and IL13 C1923T in Mauritian Indian and Chinese Han children with asthma. This case-control association study enrolled 382 unrelated Mauritian Indian children, 193 with asthma and 189 healthy controls, and 384 unrelated Chinese Han children, 192 with asthma and 192 healthy controls. The SNP loci were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism for the Chinese Han samples and TaqMan real-time quantitative PCR for the Mauritian Indian samples. In the Mauritian Indian children, there was a significant difference in the distribution of IL13 C1923T between the asthma and control groups (P=0.033). The frequency of IL13 C1923T T/T in the Mauritian Indian asthma group was significantly higher than in the control group [odds ratio (OR)=2.119, 95% confidence interval=1.048-4.285]. The Chinese Han children with asthma had significantly higher frequencies ofMS4A2 C-109T T/T (OR=1.961, P=0.001) and ADRB2 R16G A/A (OR=2.575, P=0.000) than the control group. The IL13 C1923T locus predisposed to asthma in Mauritian Indian children, which represents an ethnic difference from the Chinese Han population. TheMS4A2 C-109T T/T and ADRB2 R16G A/Agenotypes were associated with asthma in the Chinese Han children.

Serotonin regulates osteoblast proliferation and function in vitro

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1Breceptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivoantitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

The role of necroptosis in neurosurgical diseases

Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex

MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptorCTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.