RESUMEN

Aberrant activation of the JAK-STAT pathway is evident in various human diseases including cancers. Proteolysis targeting chimeras (PROTACs) provide an attractive strategy for developing novel JAK-targeting drugs. Herein, a series of CRBN-directed JAK-targeting PROTACs were designed and synthesized utilizing a JAK1/JAK2 dual inhibitor-momelotinib as the warhead. The most promising compound 10c exhibited both good enzymatic potency and cellular antiproliferative effects. Western blot analysis revealed that compound 10c effectively and selectively degraded JAK1 in a proteasome-dependent manner (DC50 = 214 nM). Moreover, PROTAC 10c significantly suppressed JAK1 and its key downstream signaling. Together, compound 10c may serve as a novel lead compound for antitumor drug discovery.

Asunto(s)

Antineoplásicos , Proliferación Celular , Janus Quinasa 1 , Proteolisis , Humanos , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 1/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proteolisis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Descubrimiento de Drogas , Estructura Molecular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Dosis-Respuesta a Droga , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo

RESUMEN

Hepatocellular carcinoma (HCC) is a major contributor to global mortality rates, but current treatment options have limitations. Advanced theranostics are needed to effectively integrate diagnosis and therapeutic of HCC. Glycyrrhetinic acid (GA) has abundant binding sites with glycyrrhetinic acid receptors (GA-Rs) on the surface of HCC cells and has also been reported to possess ligands with mitochondrial-targeting capability but with limited efficacy. Herein, we report a near-infrared (NIR) luminescent theranostic complex 1 through conjugating an iridium(III) complex to GA, which exhibits the desired photophysical properties and promotes mitochondrial-targeting capability. Complex 1 was selectively taken up by HepG2 liver cancer cells and was imaged within mitochondria with NIR emission. Complex 1 targeted mitochondria and opened mitochondrial permeability transition pores (MPTPs), resulting in ROS accumulation, mitochondrial damage, disruption of Bax/Bcl-2 equilibrium, and tumor cell apoptosis, resulting in significantly improved anticancer activity compared to GA. This work offers a methodology for developing multifunctional theranostic probes with amplified specificity and efficacy.

Asunto(s)

Carcinoma Hepatocelular , Ácido Glicirretínico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Medicina de Precisión , Iridio/farmacología , Iridio/química , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/química , Mitocondrias/metabolismo , Línea Celular Tumoral

RESUMEN

Temozolomide (TMZ) is an anticancer agent used to treat glioblastoma, typically following radiation therapy and/or surgical resection. However, despite its effectiveness, at least 50% of patients do not respond to TMZ, which is associated with repair and/or tolerance of TMZ-induced DNA lesions. Studies have demonstrated that alkyladenine DNA glycosylase (AAG), an enzyme that triggers the base excision repair (BER) pathway by excising TMZ-induced N3-methyladenine (3meA) and N7-methylguanine lesions, is overexpressed in glioblastoma tissues compared to normal tissues. Therefore, it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glioblastomas. Herein, we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods. As a proof-of-concept, this assay was used to screen 1440 food and drug administration-approved drugs against AAG, resulting in the repurposing of sunitinib as a potential AAG inhibitor. Sunitinib restored glioblastoma (GBM) cancer cell sensitivity to TMZ, inhibited GBM cell proliferation and stem cell characteristics, and induced GBM cell cycle arrest. Overall, this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

RESUMEN

Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed in human diseases, especially cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues. Currently, drug resistance is a main impediment for cancer therapy. KDMs have been found to mediate drug tolerance of many cancers via altering the metabolic profile of cancer cells, upregulating the ratio of cancer stem cells and drug-tolerant genes, and promoting the epithelial-mesenchymal transition and metastatic ability. Moreover, different cancers show distinct oncogenic addictions for KDMs. The abnormal activation or overexpression of KDMs can alter gene expression signatures to enhance cell survival and drug resistance in cancer cells. In this review, we describe the structural features and functions of KDMs, the KDMs preferences of different cancers, and the mechanisms of drug resistance resulting from KDMs. We then survey KDM inhibitors that have been used for combating drug resistance in cancer, and discuss the opportunities and challenges of KDMs as therapeutic targets for cancer drug resistance.

Asunto(s)

Histonas , Neoplasias , Humanos , Histonas/química , Lisina/química , Lisina/metabolismo , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Neoplasias/genética

RESUMEN

Herein, for the first time, we present a novel solution method for controllable synthesis of the overlooked cubic phase Cu2GeTe3 nanocrystals. The resulting Cu2GeTe3 nanocrystals are of high quality with monodispersed size and uniform shape. Optical characterization demonstrates that Cu2GeTe3 nanocrystals have a broad absorption in the visible to near-infrared region. Furthermore, an optoelectronic device based on Cu2GeTe3 nanocrystals exhibits excellent stability, reproducibility and responsivity. The novel synthetic route presented here not only can open a new avenue for fabricating Cu2GeTe3 nanocrystals, especially at the nanoscale, but also may further expand their applications.

RESUMEN

Acetylation of NF-κB's RelA subunit at lysine-310 (AcLys310) helps to maintain constitutive NF-κB activity in cancers such as triple-negative breast cancer (TNBC). Bromodomain-containing factor BRD4 binds to acetylated RelA to promote the activity of NF-κB. Hence, interfering with the acetylated RelA-BRD4 interaction is a potential strategy for treating NF-κB-driven TNBC. Here, a new compound 13a was obtained by structural optimization and modification of our previously reported compound. In comparison with the well-known BRD4 inhibitor (+)-JQ1, 13a showed more potent anticancer activity in NF-κB-active MDA-MB-231 cells. Mechanistically, 13a antagonized the protein-protein interaction (PPI) between BRD4 and acetylated RelA, decreased levels of IL-6, IL-8, Snail, Vimentin, and ZEB1, induced cell senescence and DNA damage, and weakened the adhesion, metastasis, and invasion ability of TNBC cells. Our results provide insights into avenues for the further development of potent BRD4-acetylated RelA PPI inhibitors. Moreover, our findings highlight the effectiveness and feasibility of blocking the interaction between BRD4 and acetylated RelA against NF-κB-active cancers, and of screening antagonists of this PPI.

Asunto(s)

Antineoplásicos/farmacología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Indoles/farmacología , FN-kappa B/antagonistas & inhibidores , Ácidos Pentanoicos/farmacología , Factores de Transcripción/antagonistas & inhibidores , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/química , Modelos Moleculares , Estructura Molecular , FN-kappa B/metabolismo , Ácidos Pentanoicos/química , Relación Estructura-Actividad , Factores de Transcripción/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología

RESUMEN

The ubiquitin-proteasome system oversees cellular protein degradation in order to regulate various critical processes, such as cell cycle control and DNA repair. Ubiquitination can serve as a marker for mutation, chemical damage, transcriptional or translational errors, and heat-induced denaturation. However, aberrant ubiquitination and degradation of tumor suppressor proteins may result in the growth and metastasis of cancer. Hence, targeting the ubiquitination cascade reaction has become a potential strategy for treating malignant diseases. Meanwhile, computer-aided methods have become widely accepted as fast and efficient techniques for early stage drug discovery. This review summarizes ubiquitination regulators that have been discovered via virtual screening and their applications for cancer treatment.

RESUMEN

BACKGROUND: It has been reported that the polyadenylate-binding protein-interacting protein 1 (PAIP1) pathway is closely connected with the progression of some malignant tumors. Here we examined the potential functional mechanism of PAIP1 in tongue squamous cell carcinoma (TSCC). METHODS: PAIP1 was knocked down in TSCC cell lines and proliferation and apoptosis in vitro analyzed. The molecular features of TSCC were determined using quantitative proteome and succinylome analyses. The results were confirmed in the mouse model. RESULTS: PAIP1 promoted cell proliferation and inhibited apoptosis. Its knockdown decreased Ki67 and Pcna expressions and increased Bax/Bcl2 index and Caspase-3 expression. Bioinformatics analysis for proteomics revealed that PAIP1 knockdown correlated with the changes in differential protein expression. CONCLUSIONS: Upregulation of PAIP1 induces cell proliferation and inhibits apoptosis in TSCC; PAIP1 might be a diagnostic biomarker and a significant drug target.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de la Lengua , Animales , Apoptosis , Carcinoma de Células Escamosas/genética , Proteínas Portadoras/genética , Línea Celular Tumoral , Proliferación Celular , Ratones , Factores de Iniciación de Péptidos , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN , Lengua , Neoplasias de la Lengua/genética

RESUMEN

This article was designed by using a network pharmacological approach to reveal the therapeutic targets and molecular mechanisms of oxyresveratrol (Oxyres) treating colorectal cancer (CRC). Furthermore, several bioinformatic findings would be validated. Pathogenetic targets of CRC and pharmacological targets of Oxyres were identified by web-available databases. All identifiable biotargets were collected for functional enrichment analyses to reveal the biological processes and signaling pathways of Oxyres treating CRC. In addition, human CRC, non-CRC samples, and cell line study were used to validate the predictive biotargets of Oxyres treating CRC. In network pharmacological analyses, top therapeutic targets of mitogen-activated protein kinase 1 (MAPK1), insulin growth factor 1 (IGF1), hematopoietic prostaglandin D synthase (HPGDS), GTPase HRas (HRAS), and cytochrome P450 2C9 (CYP2C9) in Oxyres treating CRC were identified, respectively. As shown in functional analysis, biological processes of Oxyres treating CRC were mainly involved in modulating cell communication, signal transduction, apoptosis, cell motility, cell proliferation, and lipid metabolism. Furthermore, top 10 signaling pathways of Oxyres treating CRC were identified, respectively. In human study, CRC samples resulted in increased neoplastic expressions of Ki-67, MAPK1, IGF1, characterized with clinical imaging inspection, pathological diagnosis, and altered blood lipids in these CRC cases. In cell culture study, Oxyres-dosed CRC cells exhibited reduced cell proliferation, promoted cellular apoptosis. Furthermore, significantly decreased proteins of intracellular Ki-67, MAPK1, and IGF1 were observed in Oxyres-dosed cells when compared to those in controls. Collectively, anti-CRC pharmacological activity of Oxyres may be mainly associated with induction of apoptosis and suppression of cell proliferation as revealed in bioinformatic findings. In addition, all core biotargets and molecular mechanisms of Oxyres treating CRC are unveiled respectively. Interestingly, the identifiable MAPK1, IGF1 biotargets may be potential molecules for treating and screening CRC.

Asunto(s)

Neoplasias Colorrectales/tratamiento farmacológico , Biología Computacional/métodos , Extractos Vegetales/farmacología , Estilbenos/farmacología , Anciano , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos

RESUMEN

BACKGROUND AND PURPOSE: Autophagy is a critical cellular catabolic process in cell homoeostasis and brain function. Recent studies indicate that receptor for activated C kinase 1 (RACK1) is involved in autophagosome formation in Drosophila and mice, and that it plays an essential role in morphine-associated memory. However, the exact mechanism of the role of RACK1 in morphine-induced autophagy is not fully understood. EXPERIMENTAL APPROACH: SH-SY5Y cells were cultured and morphine, rapamycin, 3-methyladenine and RACK1 siRNA were used to evaluate the regulation of RACK1 protein in autophagy. Western blotting and immunofluorescence were used to assess protein expression. KEY RESULTS: Activation of autophagy (i.e. autophagosome accumulation and an increase in the LC3-II/LC3-I ratio) induced by morphine contributes to the maintenance of conditioned place preference (CPP) memory in mice. Moreover, morphine treatment significantly increased Beclin-1 expression and decreased the p-mTOR/mTOR and SQSTM1/p62 levels, whereas knockdown of RACK1 prevented morphine-induced autophagy in vitro. Furthermore, we found that in the mouse hippocampus, knockdown of RACK1 also markedly suppressed morphine-induced autophagy (decreased LC3-II/LC3-I ratio and increased p-mTOR/mTOR ratio). Importantly, morphine-induced autophagy in a RACK1-dependent manner. Conversely, morphine-induced RACK1 upregulation in vitro is partially inhibited by autophagy feedback. CONCLUSIONS AND IMPLICATIONS: Our findings revealed a critical role for RACK1-dependent autophagy in morphine-promoted maintenance of CPP memory in mice and supported the notion that control of RACK1-dependent autophagic pathways may become an important target for novel therapeutics for morphine-associated memory.

Asunto(s)

Autofagia , Morfina , Animales , Beclina-1/genética , Línea Celular , Ratones , Morfina/farmacología , Neuronas , Receptores de Cinasa C Activada

RESUMEN

In this study, colorectal cancer (CRC)-diseased targets and resveratrol (Res)-associated targets were combined and constructed by the use of grouped databases for identification of the predicted targets. After production of target-functional protein interaction network of Res anti-CRC, the topological analysis was used to create the core targets of Res anti-CRC. All core targets performed the analyses of biological function and pathway enrichment to optimize the biological processes and key signaling pathways of Res anti-CRC. The resultant five core therapeutic targets of Res anti-CRC were identified as protein kinase B1 (AKT1), interleukin 6 (IL6), Tumor protein p53 (TP53), vascular endothelial growth factor, and mitogen-activated protein kinase 1, respectively. Biological processes of Res anti-CRC were predominantly associated with regulating apoptosis, immune response, cellular communication, signal transduction, and metabolism of the nuclide. In addition, the top 10 key signaling pathways were identified, respectively. In human CRC sample assays, CRC histologic sections showed elevated expression of AKT1 and IL6 proteins, accompanied with abnormal changes in blood molecules. In pharmacological experiments of Res anti-CRC in vitro, Res-treated HCT116 cells showed inhibited cell growth, induced cell death. In addition, downregulation of intracellular AKT1 and IL6 expression were checked in Res-treated HCT116 cells. Taken together, these bioinformatic findings and preliminary validated data uncovered pharmacological molecular mechanisms associated with Res anti-CRC, and further identified top five core therapeutic targets. Beneficially, these five predicted targets might serve as potential biomolecules for anti-CRC treatment.

RESUMEN

Strobilurin fungicides play a crucial role in protecting plants against different pathogens and securing food supplies. A series of 1,2,3-thiadiazole and thiazole-based strobilurins were rationally designed, synthesized, characterized, and tested against various fungi. Introduction of 1,2,3-thiadiazole greatly improved the fungicidal activity of the target molecules. Compounds 8a, 8c, 8d, and 10i exhibited a relatively broad spectrum of fungicidal activity. Compound 8a showed excellent activities against Gibberella zeae, Sclerotinia sclerotiorum, and Rhizoctonia cerealis with median effective concentrations (EC50) of 2.68, 0.44, and 0.01 µg/mL, respectively; it was much more active than positive controls enestroburin, kresoxim-methyl, and azoxystrobin with EC50 between 0.06 and 15.12 µg/mL. Comparable or better fungicidal efficacy of compound 8a compared with azoxystrobin and trifloxystrobin against Sphaerotheca fuliginea and Pseudoperonspera cubensis was validated in cucumber fields at the same application dosages. Therefore, compound 8a is a promising fungicidal candidate worthy of further development.

Asunto(s)

Fungicidas Industriales/síntesis química , Fungicidas Industriales/farmacología , Tiadiazoles/química , Tiadiazoles/farmacología , Ascomicetos/efectos de los fármacos , Ascomicetos/fisiología , Cucumis sativus/microbiología , Fungicidas Industriales/química , Estructura Molecular , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Tiadiazoles/síntesis química

RESUMEN

The inhibition of free ammonia (FA) to the granule-based enhanced biological phosphorus removal (EBPR) system and the recoverability from macro- to micro-scale were investigated in this study. FA was found to seriously deteriorate the EBPR performance and sludge characteristic (settleability and morphology). The FA inhibitory threshold of 17.76 mg NL(-1) was established. Acclimation phenomenon took place when poly-phosphate accumulating organisms (PAOs) were exposed for long time to constant FA concentration (8.88 mg NL(-1)). The repressed polysaccharides excretion could lead to breaking the stability and integrity of the granules. Therefore, the reduced particle size and granule disintegration were observed. The molecular analysis revealed that FA had a significant influence on the microbial communities and FA inhibition may provide a competitive advantage to glycogen accumulating organisms (GAOs) over PAOs. Interestingly, the community composition was found irreversible by recovery (Dice coefficients, 36.3%), although good EBPR performance was re-achieved.

Asunto(s)

Amoníaco/metabolismo , Fósforo/aislamiento & purificación , Aguas del Alcantarillado/química , Secuencia de Bases , Biodegradación Ambiental , Análisis de la Demanda Biológica de Oxígeno , Electroforesis en Gel de Gradiente Desnaturalizante , Espacio Extracelular/química , Glucógeno/metabolismo , Tamaño de la Partícula , Polihidroxialcanoatos/biosíntesis , Reacción en Cadena de la Polimerasa , Polifosfatos/metabolismo , ARN Ribosómico 16S/genética , Volatilización

RESUMEN

An optimal operating condition for ammonia removal at low temperature, based on fully coupled activated sludge model (FCASM), was determined in a full-scale oxidation ditch process wastewater treatment plant (WWTP). The FCASM-based mechanisms model was calibrated and validated with the data measured on site. Several important kinetic parameters of the modified model were tested through respirometry experiment. Validated model was used to evaluate the relationship between ammonia removal and operating parameters, such as temperature (T), dissolved oxygen (DO), solid retention time (SRT) and hydraulic retention time of oxidation ditch (HRT). The simulated results showed that low temperature have a negative effect on the ammonia removal. Through orthogonal simulation tests of the last three factors and combination with the analysis of variance, the optimal operating mode acquired of DO, SRT, HRT for the WWTP at low temperature were 3.5 mg L(-1), 15 d and 14 h, respectively.

Asunto(s)

Amoníaco/aislamiento & purificación , Frío , Modelos Químicos , Aguas del Alcantarillado , Calibración , Oxidación-Reducción , Aguas Residuales

RESUMEN

This study investigated the long-term effect of nitrite on the granule-based enhanced biological phosphorus removal (EBPR) system and the reversibility from macro- to micro-scale. Nitrite was found to seriously deteriorate the EBPR performance and result in severe sludge bulking. The inhibited polysaccharides excretion could lead to breaking the stability and integrity of the granules. Therefore, the reduced particle size and granule disintegration were observed. In this study, granules with lower ratio of proteins to polysaccharides (1.76) had better structure and function than the higher (3.84). Experimental results demonstrated that the microbial community structure was largely changed due to the presence of nitrite. In comparison, glycogen accumulating organisms (GAOs) had stronger resistibility and higher recovery rate than poly-phosphate accumulating organisms (PAOs). Interestingly, the community composition was unable to recover (Dice coefficients, 33.0%), although good EBPR performance was achieved only by propagating other types of PAOs.

Asunto(s)

Bacterias/efectos de los fármacos , Reactores Biológicos/microbiología , Restauración y Remediación Ambiental/métodos , Nitritos/farmacología , Fósforo/aislamiento & purificación , Aguas del Alcantarillado/microbiología , Bacterias/metabolismo , Biología Computacional , Electroforesis en Gel de Gradiente Desnaturalizante , Glucógeno/análisis , Hibridación Fluorescente in Situ , Microscopía Fluorescente , Tamaño de la Partícula , Fósforo/metabolismo , Polisacáridos/análisis , Proteínas/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Aguas del Alcantarillado/análisis

RESUMEN

Influence of Cr(VI) on P removal in enhanced biological phosphorus removal (EBPR) system was investigated with respect to the composition of poly-phosphate-accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), the transformation of poly-ß-hydroxyalkanoates (PHA) and glycogen, enzymes' activities, and the intracellular Cr. Whether EBPR system could revive after Cr(VI) shock was also explored. Results showed P removal performance was completely inhibited by Cr(VI) with the concentration more than 5 mg L(-1). PAOs were more sensitive to Cr(VI) than GAOs and the other bacteria were. PHA consumption, glycogen synthesis and adenylate kinase's activity had been inhibited by 5 mg L(-1) Cr(VI). Both adenylate kinase's activity and P removal efficiency were negatively correlated with the intracellular Cr. Recovery experiments revealed that P removal performance with 5 mg L(-1) Cr(VI) shock could revive after a 2-day recovery treatment, while systems with high level Cr(VI) (20 and 60 mg L(-1)) shock could not.

Asunto(s)

Bacterias/metabolismo , Reactores Biológicos , Cromo/toxicidad , Fósforo/aislamiento & purificación , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/análisis , Purificación del Agua/métodos , Adenilato Quinasa/metabolismo , Bacterias/efectos de los fármacos , Análisis de la Demanda Biológica de Oxígeno , Cromo/análisis , Glucógeno/metabolismo , Hibridación Fluorescente in Situ , Microscopía Fluorescente , Polihidroxialcanoatos/metabolismo , Espectrofotometría Atómica

RESUMEN

A symbiotic ecosystem between Tubificidae and microorganisms was established at a full-scale wastewater treatment plant (WWTP). In this ecosystem Tubificidae were inoculated, and then adhered to the outer layers of carrier materials in an oxidation tank. During the long-term treatment of sewage volumes of 20,000 m(3)d(-1), the excess sludge production rate was reduced from 0.21 to 0.051 kg m(-3) and sludge settleability was significantly improved. When the influent concentrations of COD, NH(4)(+)-N, PO(4)(-)-P, and SS were in the ranges of 130.0-459.0 mg L(-1), 14.2-27.5 mg L(-1), 1.6-7.0 mg L(-1), and 60.0-466.0 mg L(-1), respectively, the COD and SS removal efficiency was increased by 8.7% and 13.6% within the symbiotic system compared to the control without Tubificidae. In addition, NH(4)(+)-N and phosphorus removal efficiency can also be improved. The results showed that both sludge reduction and nutrient removal were enhanced simultaneously significantly within the system utilizing the symbiotic interactions of Tubificidae and microorganisms.

Asunto(s)

Bacterias/metabolismo , Oligoquetos/metabolismo , Aguas del Alcantarillado/microbiología , Aguas del Alcantarillado/parasitología , Eliminación de Residuos Líquidos/métodos , Amoníaco/aislamiento & purificación , Animales , Biodegradación Ambiental , Análisis de la Demanda Biológica de Oxígeno , Oligoquetos/crecimiento & desarrollo , Fósforo/aislamiento & purificación , Reproducción/fisiología , Volatilización , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminación del Agua

RESUMEN

In animal cells, myo-inositol is an important regulatory molecule in several physiological and biochemical processes, including signal transduction and membrane biogenesis. However, the fundamental biological functions of myo-inositol are still far from clear in plants. Here, we report the genetic characterization of three Arabidopsis thaliana genes encoding D-myo-inositol-3-phosphate synthase (MIPS), which catalyzes the rate-limiting step in de novo synthesis of myo-inositol. Each of the three MIPS genes rescued the yeast ino1 mutant, which is defective in yeast MIPS gene INO1, and they had different dynamic expression patterns during Arabidopsis embryo development. Although single mips mutants showed no obvious phenotypes, the mips1 mips2 double mutant and the mips1 mips2 mips3 triple mutant were embryo lethal, whereas the mips1 mips3 and mips1 mips2⁺/⁻ double mutants had abnormal embryos. The mips phenotypes resembled those of auxin mutants. Indeed, the double and triple mips mutants displayed abnormal expression patterns of DR5:green fluorescent protein, an auxin-responsive fusion protein, and they had altered PIN1 subcellular localization. Also, membrane trafficking was affected in mips1 mips3. Interestingly, overexpression of PHOSPHATIDYLINOSITOL SYNTHASE2, which converts myo-inositol to membrane phosphatidylinositol (PtdIns), largely rescued the cotyledon and endomembrane defects in mips1 mips3. We conclude that myo-inositol serves as the main substrate for synthesizing PtdIns and phosphatidylinositides, which are essential for endomembrane structure and trafficking and thus for auxin-regulated embryogenesis.

Asunto(s)

Arabidopsis/embriología , Ácidos Indolacéticos/metabolismo , Fosfatos de Inositol/metabolismo , Inositol/metabolismo , Membranas Intracelulares/metabolismo , Fosfatidilinositoles/metabolismo , Arabidopsis/enzimología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico/genética , Cotiledón/genética , Cotiledón/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Prueba de Complementación Genética , Liasas Intramoleculares/genética , Luz , Modelos Biológicos , Mutación/genética , Mio-Inositol-1-Fosfato Sintasa/metabolismo , Fenotipo , Hojas de la Planta/embriología , Hojas de la Planta/genética , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Semillas/citología , Semillas/genética , Estrés Fisiológico/genética

RESUMEN

The growth kinetics of aquatic worms was investigated from juvenile to decline phase for 18 weeks by cultivating with activated sludge in batch test. Results showed that the growth of aquatic worms well fit Gauss function for cultivating 18 weeks. The maximum specific growth rate, growth yield of aquatic worms and sludge reduction rate was 0.41 d(-1), 0.32 and 25.5%, respectively. When the concentration of substrate and dissolved oxygen change from low to high, the relationship between the specific growth rate with dissolved oxygen, and substrate concentration meet the Monod equation. Compared with the dissolved oxygen, the substrate concentration had greater effect on the specific growth rate of aquatic worms, and aquatic worms can live in the environment with low dissolved oxygen. Furthermore, the breath test showed the oxygen uptake rate of aquatic worms was almost 6.39, 10.10, 11.31 and 5.74 mg x (L x g x h)(-1) from juvenile to decline phase, the dissolved oxygen demand of the rapid growth and mature stage was higher than juvenile and decline phase.

Asunto(s)

Arguloida/crecimiento & desarrollo , Arguloida/fisiología , Eliminación de Residuos/métodos , Aguas del Alcantarillado/química , Animales , Organismos Acuáticos/crecimiento & desarrollo , Organismos Acuáticos/fisiología , Técnicas de Cultivo , Conducta Alimentaria , Cinética , Oxígeno/metabolismo , Eliminación de Residuos Líquidos/instrumentación , Eliminación de Residuos Líquidos/métodos

RESUMEN

This paper assesses the potential of NanoChem zeolite for ammonia removal from synthetic solution and actual landfill leachate. The data from experiments in batch study were applied to Langmuir isotherm. The saturated amount of NH4(+) -N adsorbed per unit weight of NanoChem zeolite was about 364 mg x g(-1), which yield significantly 3-30 times higher ammonium adsorption capacity than nature zeolite and Microporous molecular sieves. The results of batch study showed that the contact time needed at least 20 h in order to attain exchange equilibrium; the ammonia removal capacity of NanoChem zeolite increased with the increase of initial ammonia concentration, while the ammonia removal rate decreased with the increase of initial ammonia concentration; the pH had an effect on ammonia removal efficiency as it can influence both the character of the exchanging ions and the NanoChem zeolite itself; regeneration made little change on ammonia removal efficiency, repeatability was good. In column study, the NanoChem zeolite was used for high ammonia nitrogen removal such as actual landfill leachate and the ammonia nitrogen was removed 100%.

Asunto(s)

Intercambio Iónico , Nanopartículas , Compuestos de Amonio Cuaternario/aislamiento & purificación , Eliminación de Residuos Líquidos/métodos , Zeolitas/química , Adsorción , Nitrógeno/aislamiento & purificación