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关键词： Abiotic stress   Taxanes   Paclitaxel   Total phenol   Antioxidant  

摘要： The metabolic stimulation induced by abiotic stress is an efficient strategy for the production of secondary metabolites in sterile and controlled plant cell, tissue, and organ cultures. Paclitaxel (taxol), one of the most widely used therapeutic compounds for the treatment of various cancers, is mainly produced through cell culture of the European yew (Taxus baccataL.). In this work, aT. baccatacallus culture was subjected to drought stress inducedin vitroby mannitol and sorbitol (1, 2, 3, and 4%) and sucrose (6 and 8%) to evaluate its impact on physiological and biochemical traits as well as paclitaxel and 10-deacetyl baccatin III (10-DBA) production. It was observed that drought stress caused a significant increase (P< 0.05) in dry weight, proline, soluble sugars, hydrogen peroxide, lipid peroxidation, total phenolics, flavonoids, and flavonols, and a decrease in relative water content, fresh weight, relative growth rate, and cell viability. Constitutive activities of superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase were enhanced by the induced stress. The content of paclitaxel and 10-DBA was higher in stressed cultures than in the control. It can be concluded thatT. baccatacells have a protection mechanism against oxidative damage involving induced activities of enzymatic and non-enzymatic antioxidants. The induction of moderate drought stress could therefore be an effective strategy for increasing taxanes production inT. baccatacallus cultures.

关键词： Antioxidant capacity   Carotenoids   Cyanobacteria   Fatty acids   Lipids   Photosynthetic activity   Phycobiliproteins  

摘要： Cyanobacteria are able to absorb light over a wide spectral range due to the presence of photoreceptors, making it possible to modulate the production of high-value compounds by inducing specific pathways. In order to evaluate the influence of light quality in cyanobacteria metabolism,Cyanobiumsp. was grown in five different light conditions, by using low-pressure sodium vapor lamp (SOX) supplemented with low irradiances of green, red, and blue light and UV radiation compared to a control with only SOX. The effects of light supplementation on biomass productivity, photosynthetic activity, biochemical composition, and total antioxidant capacity were evaluated. No changes in biomass productivity were induced by any light supplements. The supplementation of red light triggered the production of lipids, phycocyanin, carotenoids, and total antioxidant compounds, while supplementation of green light increased the content of carbohydrates and chlorophylla. Thus, supplementation of blue light and UV radiation showed little or no improvements to the culture, whereas under UV radiation the photosynthetic activity was reduced. Overall,Cyanobiumsp. is a promising strain, mainly due to its accessibility to metabolism photoregulation as to produce various bioactive compounds.

关键词： Morphogenesis   Force   Signaling   Actomyosin   Tension   Yap   Taz   Eph   Ephrin   PIEZO   Development  

摘要： Morphogenesis is a physical process that requires the generation of mechanical forces to achieve dynamic changes in cell position, tissue shape, and size as well as biochemical signals to coordinate these events. Mechanical forces are also used by the embryo to transmit detailed information across space and detected by target cells, leading to downstream changes in cellular properties and behaviors. Indeed, forces provide signaling information of complementary quality that can both synergize and diversify the functional outputs of biochemical signaling. Here, we discuss recent findings that reveal how mechanical signaling and biochemical signaling are integrated during morphogenesis and the possible context-specific advantages conferred by the interactions between these signaling mechanisms.

关键词： Iron oxides   Nitrous oxide   Nitrification   AOA   AOB  

摘要： Purpose Iron (Fe) oxides play an important role in regulating nitrification and N2O emissions, but there is very little study on the biological-chemical comprehensive effects of Fe oxides on nitrification and N2O emissions. Materials and methods A laboratory incubation experiment was performed to evaluate the effect of goethite addition on nitrification and N2O emissions from acidic and alkaline paddy soils. Results and discussion The cumulative N2O emissions from alkaline paddy soil were significantly higher than those from acidic paddy soil, no matter whether goethite had been added or not. Adding goethite decreased the average net rate of soil nitrification in acidic paddy soil by 33.2% in comparison with the treatment without adding goethite;however, adding goethite scarcely decreased the average net rate in alkaline paddy soil. Adding goethite increased the maximal N2O emissions by 85.6% in alkaline paddy soil, but had no obvious effect in acidic paddy soil. Adding goethite significantly increased the abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB)amoAgenes in both alkaline and acidic paddy soils. High-throughput pyrosequencing of 16S rRNA gene showed that adding goethite significantly increased the relative abundance ofNitrosomonadaceaein alkaline paddy soil and that the dominant species of AOB and AOA wereNitrosomonadaceaeandNitrososphaeraceae, respectively. Conclusions N2O emissions in alkaline paddy soil were higher than those in acidic paddy soil. The enhancement of N2O emissions by goethite was more significant in alkaline paddy soil than in acidic paddy soil. Goethite stimulated the abundance ofamoAgene (both of AOB and AOA) and participated in nitrification process via chemical reaction with intermediates.

关键词： precocious puberty   DLK1   genetics   mutations  

摘要： Background: Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood. Objective: Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations. Patients: A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed. Results: Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401_404 + 8del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (<0.4 ng/mL), indicating that the deletion led to complete lack of DLK1 production. Three others rare allelic variants of DLK1 were also identified (***134=;g.-222 C>A and g.-223 G>A) in 2 girls with CPP. However, both had normal DLK1 serum levels. Conclusion: Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing.

关键词： fluoride   cerebellum   oxidative stress   proteomic  

摘要： Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.

关键词： Urea cycle disorder   Hyperammonemia   Amino acid   Acylcarnitine   Choline   N-acetylaspartic acid  

摘要： Background: Ornithine transcarbamylase deficiency (OTCD) is pleomorphic congenital hyperammonemia, in which the prognosis of the patient is determined both by genotype and environmental factors. This study investigated the clinical and biochemical characteristics of OTCD patients with different prognosis. Method: Of 35 OTCD patients, six males deceased at the first disease-onset, 17 males survived and had controllable ammonia levels after treatment, and 12 females survived through the first disease-onset but had in tractable hyperammonemia and high mortality. Fasting blood samples from patients collected at three disease stages were used for the analysis of amino acid (AA) profile, acylcarnitine profile, and micronutrients. Differences in profiles between patients and healthy controls and within patient groups were studied. Results: All OTCD patients had accumulation of glutamine, homocitrulline, lysine, glutamate, cystathionine, and pipecolic acid, as well as deficiency of citrulline, tryptophan, threonine, and carnitine. For male non-survivors, most other AAs and long-chain acylcarnitines were elevated at disease onset, of which the levels of creatine, Nacetylaspartic acid, and homoarginine were remarkably high. Male survivors and female patients had most other AAs at low to normal levels. Compared with male survivors, female patients had much lower protein-intolerance, as indicated by significantly lower levels of protein consumption indicators, including essential AAs, 1-methylhistidine, acylcarnitines et al., but high levels of ammonia. Female patients still had significantly higher levels of citrulline, homocitrulline, and citrulline/arginine compared to male survivors. Conclusion: Unique profiles were observed in each group of OTCD patients, indicating specific physiological changes that happened to them.

关键词： Flavoproteins   D-amino acids   Structure-function relationships   Protein stability   Cofactor binding  

摘要： D-amino acids research field has recently gained an increased interest since these atypical molecules have been discovered to play a plethora of different roles. In the mammalian central nervous system, D-aspartate (D-Asp) is critically involved in the regulation of glutamatergic neurotransmission by acting as an agonist of NMDA receptor. Accordingly, alterations in its metabolism have been related to different pathologies. D-Asp shows a peculiar temporal pattern of emergence during ontogenesis and soon after birth its brain levels are strictly regulated by the catabolic enzyme D-aspartate oxidase (DASPO), a FAD-dependent oxidase. Rodents have been widely used as in vivo models for deciphering molecular mechanisms and for testing novel therapeutic targets and drugs, but human targets can significantly differ. Based on these considerations, here we investigated the structural and functional properties of the mouse DASPO, in particular kinetic properties, ligand and flavin binding, oligomerization state and protein stability. We compared the obtained findings with those of the human enzyme (80% sequence identity) highlighting a different oligomeric state and a lower activity for the mouse DASPO, which apoprotein species exists in solution in two forms differing in FAD affinity. The features that distinguish mouse and human DASPO suggest that this flavoenzyme might control in a distinct way the brain D-Asp levels in different organisms.

关键词： Ferric uptake regulator   Metal binding   DNA interactions   Aliivibrio salmonicida   Electrophoretic mobility shift assay  

摘要： Iron is an essential nutrient for bacteria, however its propensity to form toxic hydroxyl radicals at high intracellular concentrations, requires its acquisition to be tightly regulated. Ferric uptake regulator (Fur) is a metal-dependent DNA-binding protein that acts as a transcriptional regulator in maintaining iron metabolism in bacteria and is a highly interesting target in the design of new antibacterial drugs. Fur mutants have been shown to exhibit decreased virulence in infection models. The protein interacts specifically with DNA at binding sites designated as 'Fur boxes'. In the present study, we have investigated the interaction between Fur from the fish pathogenAliivibrio salmonicida(AsFur) and its target DNA using a combination of biochemical and in silico methods. A series of target DNA oligomers were designed based on analyses of Fur boxes from other species, and affinities assessed using electrophoretic mobility shift assay. Binding strengths were interpreted in the context of homology models of AsFur to gain molecular-level insight into binding specificity.

关键词： PFASs   Siberian tiger   Daily intake   Biochemical parameters  

摘要： Per- and polyfluoroalkyl substances (PFASs) have been ubiquitously detected in the environment and marine animals. However, little is known about these substances and their associations with health parameters in wild terrestrial mammals. In this study, we determined PFAS levels and distribution in the blood of captive Siberian tigers in Harbin, China, and evaluated potential exposure pathways by daily intake. In addition, for the first time, we explored the associations between serum PFAS concentrations and clinical parameters. Results showed that perfluorooctanoate (PFOA) was the dominant PFAS compound in blood (accounting for 64%), followed by perfluorooctanesulfonate (PFOS). In addition, 6:2 chlorinated polyfluorinated ether sulfonate (6:2 CI-PFESA) concentrations were also detected in blood and dietary food. Furthermore, significant positive age relationships were observed for levels of perfluoroheptanoate (PFHpA), PFOA, PFOS, and 6:2 CI-PFESA in the blood of female tigers. Results showed that PFOA and PFOS in dietary food accounted for over 70% of total daily intake of PFASs, indicating that meat consumption is a predominant exposure pathway in tigers. We also found positive associations between higher exposure to PFASs (including PFOA, PFOS, and 6:2 CI-PFESA) and elevated serum levels of alanine transaminase (ALT), a marker of liver damage. Thus, comprehensive health assessments of PFAS burdens in wildlife are needed. (C) 2020 Elsevier Ltd. All rights reserved.