hybrids

杂种
  • 文章类型: Journal Article
    酵母优化对于提高啤酒生产的质量和效率至关重要。世界上消费最广泛的饮料之一。在这种情况下,稀有交配杂交是酵母优化产生新的和改进的非GMO菌株的有前途的技术。这种技术的局限性在于缺乏有关可与酿酒酵母杂交的酵母菌株的知识和可比数据,可能是啤酒生产中最重要的酵母品种。酵母属酵母,Naumovozyma,Nakaseomyces和Kazachstania已被描述为能够与酿酒酵母形成杂种。在本研究中,在酿造条件下分析了242株酵母菌株,包括酵母属物种(S.酿酒酵母,S.kudriavzevii,S.uvarum,S.eubayanus,美国悖论,S.mikatae,S.jurei和S.arboricola)和非酵母属物种(Naumovozyma,Nakaseomyces和Kazaschtania),代表到研究开始时描述的全部遗传变异性(物种和亚群)。通过监测发酵期间的重量损失来分析发酵曲线,以确定动力学参数和CO2产生。进行代谢分析以确定糖(麦芽三糖,麦芽糖和葡萄糖),醇(乙醇,甘油和2,3-丁二醇)和有机酸(苹果酸,琥珀酸和乙酸)。麦芽糖和麦芽三糖是啤酒麦芽汁中的主要糖。消耗这些糖的能力决定了最终产品的特性。然后对物种进行数据集比较,亚群和隔离源级别。在这项研究中获得的结果表明,存在于酵母属和该属的每个物种内的巨大表型变异性,这可能有助于优化酿造混合动力车的产生。在酿造条件下可以发现具有不同发酵能力和发酵行为的酵母。酿酒酵母,S.uvarum和S.eubayanus是含有与商业菌株具有相似发酵性能的菌株的物种。
    Yeast optimisation has been crucial in improving the quality and efficiency of beer production, one of the world\'s most widely consumed beverages. In this context, rare mating hybridisation is a promising technique for yeast optimization to generate novel and improved non-GMO strains. The limitation of this technique is the lack of knowledge and comparable data on yeast strains hybridisable to Saccharomyces cerevisiae, probably the most important yeast species in beer production. Yeast from the genera Saccharomyces, Naumovozyma, Nakaseomyces and Kazachstania have been described to be able to form hybrids with S. cerevisiae. In the present study, 242 yeast strains were analysed under brewing conditions, including Saccharomyces species (S. cerevisiae, S. kudriavzevii, S. uvarum, S. eubayanus, S. paradoxus, S. mikatae, S. jurei and S. arboricola) and non-Saccharomyces species (Naumovozyma, Nakaseomyces and Kazaschtania), representing the full genetic variability (species and subpopulations) described up to the start of the study. The fermentation profile was analysed by monitoring weight loss during fermentation to determine kinetic parameters and CO2 production. Metabolic analysis was performed to determine the concentration of sugars (maltotriose, maltose and glucose), alcohols (ethanol, glycerol and 2,3-butanediol) and organic acids (malic acid, succinic acid and acetic acid). Maltose and maltotriose are the predominant sugars in beer wort. The ability to consume these sugars determines the characteristics of the final product. Dataset comparisons were then made at species, subpopulation and isolation source level. The results obtained in this study demonstrate the great phenotypic variability that exists within the genus Saccharomyces and within each species of this genus, which could be useful in the generation of optimised brewing hybrids. Yeasts with different fermentative capacities and fermentative behaviours can be found under brewing conditions. S. cerevisiae, S. uvarum and S. eubayanus are the species that contain strains with similar fermentation performance to commercial strains.
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  • 文章类型: Journal Article
    阿尔茨海默病(AD)是一种进行性神经退行性疾病,可导致认知功能下降和记忆障碍。它的特征是淀粉样β(Aβ)斑块的积累,tau蛋白的异常磷酸化形成神经原纤维缠结,通常伴有神经炎症和氧化应激,导致神经元丢失和脑萎缩.目前,临床抗AD药物大多是单靶点,提高AD患者的认知能力,但未能有效减缓AD的进展。因此,研究有效的多靶点AD药物已成为亟待解决的问题。羟基肉桂酸的主要衍生物,咖啡酸,和阿魏酸,广泛存在于自然界中,具有许多药理活性,如抗菌剂,抗氧化剂,抗炎,神经保护,抗Aβ沉积,等等。AD的发生发展常伴有病理,如氧化应激,神经炎症,和Aβ沉积,表明咖啡酸和阿魏酸可用于抗AD药物的研究。因此,在这篇文章中,综述了近年来以咖啡酸和阿魏酸为基础的多靶点抗AD衍生物,并讨论了肉桂酸衍生物作为骨架化合物的新设计方向。希望本综述能为基于肉桂酸衍生物的抗AD药物提供一些有用的策略。
    Alzheimer\'s Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aβ) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aβ deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aβ deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.
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  • 文章类型: Journal Article
    对来自6种Colocasia(天南星科)的17个样品的完整叶绿体基因组进行了测序,组装,并与两个先前报道的来自芋(Colocasiaesculenta)的完整基因组序列进行比对。分析为东南亚的芋和密切相关的野生科罗卡西亚物种提供了良好的系统发育树。两个叶绿体谱系(CI和CII)形成了明确定义的单倍型组,并在被称为var的栽培芋中发现。esculenta(dasheen,CI),var.antiquorum(eddoe,CII),在广泛的,共生野生形式称为var。水草(CI)。在被称为var的野生芋中也发现了第三谱系(CIII)。水草和野生物种C.lihengiae,C.formosana,和C.海绵体。我们建议三种不同的情况来解释CIII野生芋的分组(C.esculenta)与其他野生Colocasia物种。C.esculenta和未知亲本物种中的叶绿体谱系CI和CIII可能涉及尚未过时的杂交史,叶绿体捕获,和范围扩展。在进一步研究作物的形态和遗传多样性后,可能需要对C.esculenta进行大量的分类学修订。在野生种群中,和密切相关的野生物种。结果还指出,孟加拉三角洲是未来研究热带湿地芋起源的主要兴趣区域。
    Complete chloroplast genomes of 17 samples from six species of Colocasia (Araceae) were sequenced, assembled, and aligned together with two previously reported complete genome sequences from taro (Colocasia esculenta). Analysis provides a well-supported phylogenetic tree for taro and closely-related wild Colocasia species in Southeast Asia. Two chloroplast lineages (CI and CII) form a well-defined haplotype group and are found in cultivated taros known as var. esculenta (dasheen, CI), var. antiquorum (eddoe, CII), and in a widespread, commensal wild form known as var. aquatilis (CI). A third lineage (CIII) is also found in wild taros known as var. aquatilis and in the wild species C. lihengiae, C. formosana, and C. spongifolia. We suggest three different scenarios to explain the grouping of CIII wild taros (C. esculenta) with other wild Colocasia species. Chloroplast lineages CI and CIII in C. esculenta and an unknown parent species may be involved in an as yet undated history of hybridization, chloroplast capture, and range extension. Substantial taxonomic revision may be needed for C. esculenta after further studies of morphological and genetic diversity within the crop, in wild populations, and in closely related wild species. The results also point to the Bengal delta as a region of key interest for future research on the origins of tropical wetland taros.
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  • 文章类型: Journal Article
    通过表面改性制备了可光固化的有机-无机杂化复合材料,并利用连续辊对辊制造策略制造了3D图案结构。纳米晶体的表面是用双功能配体设计的,该配体是丙烯酸2-羧乙酯,其一端具有羧酸部分,另一端具有丙烯酸酯官能度部分,产生丙烯酸酯官能化纳米晶体。通过使用软雕刻模具的UV固化以2.5m/min的速度连续制造微尺度3D图案(每侧测量为147μm)。利用傅里叶变换红外光谱研究了功能化纳米晶的表面性质及其紫外光固化条件。使用扫描电子显微镜测量3D膜的形态。销盘式摩擦计测量显示官能化颗粒和树脂之间的相互作用得到改善。
    Photocurable hybrid organic-inorganic composites were prepared via surface modification and 3D-patterned structures were fabricated by utilizing a continuous roll-to-roll manufacturing strategy. The surfaces of nanocrystals were engineered with a bifunctional ligand that is a 2-carboxyethyl acrylate, which possesses a carboxylic acid moiety at one end and an acrylate functionality moiety at the other end, yielding acrylate-functionalized nanocrystals. Micro-scale 3D patterns (protruding pyramidal shapes with each side measuring 147 μm) were continuously manufactured at a speed of 2.5 m/min via UV curing with a soft engraved mold. The surface properties of the functionalized nanocrystals and their UV curing condition were explored with Fourier transform infrared spectroscopy. The morphology of the 3D film was measured using scanning electron microscopy. A pin-on-disk tribometer measurement revealed an improved interaction between the functionalized particles and resins.
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  • 文章类型: Journal Article
    通过促进物种形成和生态多样化,杂交和多倍化在维管植物中很常见,也是生物多样性的重要驱动因素。在杂种和异源多倍体生物多样性研究中进行广泛的合成发现的主要限制是缺乏标准化的框架来比较研究和生物学尺度上的数据。
    这里,我提出了一个新的定量框架来研究和解释杂种和异源多倍体生物学中的模式,称为发散指数(DI)。DI框架产生标准化数据,这些数据在研究和变量之间具有可比性。为了展示如何使用DI框架来合成数据,我分析了发表的生化,生理,杂种和异源多倍体的生态性状数据。我还在杂种和多倍体生物学中应用关键的生态和进化概念来翻译名义结果,包括过犯,中介,扩展,和收缩,在连续DI空间中。
    生化,生理,生态,进化数据都可以被分析,可视化,并在DI框架中解释。DI框架特别适合标准化和比较具有非常不同尺度的变量。当使用DI框架来理解利基分歧时,生态位重叠的度量可以用来补充对质心和宽度变化的见解。
    DI框架是杂种和异源多倍体生物学的可访问框架,代表了一种灵活而直观的工具,可用于调和植物生物多样性研究中的突出问题。
    UNASSIGNED: Hybridization and polyploidization are common in vascular plants and important drivers of biodiversity by facilitating speciation and ecological diversification. A primary limitation to making broad synthetic discoveries in hybrid and allopolyploid biodiversity research is the absence of a standardized framework to compare data across studies and biological scales.
    UNASSIGNED: Here, I present a new quantitative framework to investigate and interpret patterns in hybrid and allopolyploid biology called the divergence index (DI). The DI framework produces standardized data that are comparable across studies and variables. To show how the DI framework can be used to synthesize data, I analyzed published biochemical, physiological, and ecological trait data of hybrids and allopolyploids. I also apply key ecological and evolutionary concepts in hybrid and polyploid biology to translate nominal outcomes, including transgression, intermediacy, expansion, and contraction, in continuous DI space.
    UNASSIGNED: Biochemical, physiological, ecological, and evolutionary data can all be analyzed, visualized, and interpreted in the DI framework. The DI framework is particularly suited to standardize and compare variables with very different scales. When using the DI framework to understand niche divergence, a metric of niche overlap can be used to complement insights to centroid and breadth changes.
    UNASSIGNED: The DI framework is an accessible framework for hybrid and allopolyploid biology and represents a flexible and intuitive tool that can be used to reconcile outstanding problems in plant biodiversity research.
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  • 文章类型: Journal Article
    为了提高药物发现的成功率,一个实用的策略是开始分子杂交。在单个单元中两个或更多个药效团的存在导致药理学效力大于每个单独部分的效力的总和。杂环化合物在自然界中分布非常广泛,对生命活动至关重要。苯并咪唑和恶二唑是药物化学中的特权结构,由于其广泛的生物学特性而被广泛用于药物发现和开发。通过分子杂交方法,苯并咪唑-恶二唑嵌合分子可以改善单个支架的药物样特性(如药代动力学和药效学)。苯并咪唑和恶二唑核可以稠合或使用官能团/键并入。在过去的几十年里,药物发现科学家预测,这些部分可以相互连接,产生一种新的或修饰的杂合化合物。苯并咪唑和恶二唑杂种被确定为最有效的抗癌,抗菌,抗炎,抗氧化剂,抗惊厥药,抗抑郁药,抗高血压和抗结核药。在这种情况下,本综述描述了苯并咪唑-恶二唑(1,3,4和1,2,4)杂种的生物学特性,它们可能的结构-活性关系和作用机制研究。这篇综述文章旨在激发新的想法,以寻找更活跃,毒性更小的苯并咪唑-恶二唑混合前瞻性治疗候选药物的合理设计,以及更有效的诊断试剂和病理探针。
    To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety\'s potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole-oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole-oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure-activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole-oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.
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  • 文章类型: Journal Article
    由于几个葡萄回交与最初的V.viniferaL.×V.rotundifolia(以前是Muscadiniarotundifolia)种间杂交,MrRUN1/MrRPV1基因座(对绒毛和白粉病的抗性)在表型上接近V.vinifera品种的基因型中渗入。为了检查叶枯草基因组渗入部分对果实发育过程中基因表达的影响,我们对来自不同葡萄品种和葡萄品种的单一浆果进行了RNA-seq比较研究。包括\'G5\'和两个衍生的微藤系,MrRUN1/RPV1基因座的\'MV102\'(抗性)和\'MV32\'(易感)分离。从草本高原结束到成熟阶段,对一组完整的单个浆果进行了RNA-Seq分析。对端读段在两个维尼费拉PN40024上进行比对。V4参考基因组,V.圆叶cv\“托盘\”和cv\“卡洛斯\”,以及来自NCBI原始V.rotundifoliacv\'52\'亲本的少数抗性基因。加权基因共表达网络分析(WGCNA)导致将差异表达的基因分为15个模块,这些模块优先与抗性或浆果物候和组成相关。抗性正相关转录本主要定位在从MrRUN1/MrRPV1基因座开始的12号环叶弧菌染色体的4-5Mb远端区域,而负相关的映射在直系同源葡萄属病毒区域,在连续的回交过程中,LG12的这种大末端仍然难以内部重组。在该区域以外的较低密度处也观察到了一些组成型表达的圆叶弧菌基因。抗性种质在发育中的浆果中过表达的基因,要么从轮叶弧菌渗入,要么由这些在葡萄基因组中引发,跨越各种功能组,包括钙信号转导,激素信号,转录因子,植物-病原体相关的相互作用,抗病蛋白,ROS和苯丙素生物合成。这种转录组学见解为理解这些杂种品种固有的抗病性提供了基础,并表明NIRNBSLRR触发钙信号的组成型表达。此外,这些结果说明了回交杂种中渐渗的V.rotundifolia背景引起的转录组变化的幅度,在大量功能上,大大超过了在单个抗性基因转化体中组成型表达的功能。
    Thanks to several Vitis vinifera backcrosses with an initial V. vinifera L. × V. rotundifolia (previously Muscadinia rotundifolia) interspecific cross, the MrRUN1/MrRPV1 locus (resistance to downy and powdery mildews) was introgressed in genotypes phenotypically close to V. vinifera varieties. To check the consequences of introgressing parts of the V. rotundifolia genome on gene expression during fruit development, we conducted a comparative RNA-seq study on single berries from different V. vinifera cultivars and V. vinifera × V. rotundifolia hybrids, including \'G5\' and two derivative microvine lines, \'MV102\' (resistant) and \'MV32\' (susceptible) segregating for the MrRUN1/RPV1 locus. RNA-Seq profiles were analyzed on a comprehensive set of single berries from the end of the herbaceous plateau to the ripe stage. Pair-end reads were aligned both on V. vinifera PN40024.V4 reference genome, V. rotundifolia cv \'Trayshed\' and cv \'Carlos\', and to the few resistance genes from the original V. rotundifolia cv \'52\' parent available at NCBI. Weighted Gene Co-expression Network Analysis (WGCNA) led to classifying the differentially expressed genes into 15 modules either preferentially correlated with resistance or berry phenology and composition. Resistance positively correlated transcripts predominantly mapped on the 4-5 Mb distal region of V. rotundifolia chromosome 12 beginning with the MrRUN1/MrRPV1 locus, while the negatively correlated ones mapped on the orthologous V. vinifera region, showing this large extremity of LG12 remained recalcitrant to internal recombination during the successive backcrosses. Some constitutively expressed V. rotundifolia genes were also observed at lower densities outside this region. Genes overexpressed in developing berries from resistant accessions, either introgressed from V. rotundifolia or triggered by these in the vinifera genome, spanned various functional groups, encompassing calcium signal transduction, hormone signaling, transcription factors, plant-pathogen-associated interactions, disease resistance proteins, ROS and phenylpropanoid biosynthesis. This transcriptomic insight provides a foundation for understanding the disease resistance inherent in these hybrid cultivars and suggests a constitutive expression of NIR NBS LRR triggering calcium signaling. Moreover, these results illustrate the magnitude of transcriptomic changes caused by the introgressed V. rotundifolia background in backcrossed hybrids, on a large number of functions largely exceeding the ones constitutively expressed in single resistant gene transformants.
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  • 文章类型: Journal Article
    基因型-环境相互作用由环境条件变化引起的个体基因型的不同反应组成。它的意义是一种使育种过程非常困难的现象。一方面,育种者期望稳定的基因型,即,无论环境条件如何,产量都是相似的。另一方面,为每个地区选择最佳基因型是育种者和农民面临的关键挑战之一。这项研究的目的是评估由植物育种SmoliceCo.Ltd.开发的新型玉米杂交种中基因型与环境的相互作用对谷物产量的影响。利用加性主效应和乘性相互作用(AMMI)模型。调查涉及69种玉米(ZeamaysL.)杂种,在随机完整区组设计中的五个位置进行测试,重复三次。谷物产量从8.76tha-1(Smolice中的SMH_16417)到16.89tha-1(Pswaczkowo中的SMH_16043)不等,平均产量为13.16tha-1。AMMI分析确定了基因型的显着影响,环境,以及它们对谷物产量的相互作用。方差分析表明,粮食产量总变化的25.12%是由环境因素引起的,35.20%的基因型差异,和21.18%的基因型通过环境相互作用。由于杂种SMH_1706和SMH_1707具有较高的稳定性和优异的平均谷物产量,因此推荐用于进一步的育种计划。
    Genotype-environment interaction consists of the different response of individual genotypes resulting from changing environmental conditions. Its significance is a phenomenon that makes the breeding process very difficult. On the one hand, the breeder expects stable genotypes, i.e., yielding similarly regardless of environmental conditions. On the other hand, selecting the best genotypes for each region is one of the key challenges for breeders and farmers. The aim of this study was to evaluate genotype-by-environment interaction for grain yield in new maize hybrids developed by Plant Breeding Smolice Co. Ltd., utilizing the additive main effects and multiplicative interaction (AMMI) model. The investigation involved 69 maize (Zea mays L.) hybrids, tested across five locations in a randomized complete block design with three replications. Grain yield varied from 8.76 t ha-1 (SMH_16417 in Smolice) to 16.89 t ha-1 (SMH_16043 in Płaczkowo), with a mean yield of 13.16 t ha-1. AMMI analysis identified significant effects of genotype, environment, and their interaction on grain yield. Analysis of variance indicated that 25.12% of the total variation in grain yield was due to environment factor, 35.20% to genotypic differences, and 21.18% to genotype by environmental interactions. Hybrids SMH_1706 and SMH_1707 are recommended for further breeding programs due to their high stability and superior average grain yield.
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  • 文章类型: Journal Article
    化学污染物和/或气候变化有可能打破物种之间的生殖障碍并促进杂交。混合带可能是由于环境梯度和以前的异形种群之间的二次接触而产生的。或者由于引入了非本地物种。在淡水生态系统中,现场观察表明,水质和化学性质的变化,由于污染和气候变化,与杂交频率增加相关。水质的物理和化学干扰可以改变感官环境,从而影响鱼类之间的化学和视觉交流。此外,多种化合物(例如药物,金属,杀虫剂,和工业污染物)可能会损害鱼类的生理机能,潜在影响与配偶选择相关的表型性状(例如信息素生产,求爱,和着色)。尽管变暖的水域导致了有记录的范围变化,化学污染在淡水生态系统中无处不在,很少有研究测试有关这些压力源如何促进杂交以及这对生物多样性和物种保护意味着什么的假设。通过跨学科(即生态毒理学和进化生物学)的系统文献综述,我们评估生物相互作用,毒性机制,以及物理和化学环境应激源(即化学污染和气候变化)在破坏配偶偏好和诱导淡水鱼种间杂交中的作用。我们的研究表明,气候变化驱动的水质和化学污染变化可能会影响对配偶选择至关重要的视觉和化学交流,从而促进淡水生态系统中鱼类之间的杂交。为未来的研究和保护管理提供信息,我们强调进一步研究以确定影响配偶选择的化学和物理应激源的重要性,了解这些互动背后的机制,确定它们发生的浓度,并评估它们对个人的影响,人口,物种,人类世的生物多样性。
    Chemical pollutants and/or climate change have the potential to break down reproductive barriers between species and facilitate hybridization. Hybrid zones may arise in response to environmental gradients and secondary contact between formerly allopatric populations, or due to the introduction of non-native species. In freshwater ecosystems, field observations indicate that changes in water quality and chemistry, due to pollution and climate change, are correlated with an increased frequency of hybridization. Physical and chemical disturbances of water quality can alter the sensory environment, thereby affecting chemical and visual communication among fish. Moreover, multiple chemical compounds (e.g. pharmaceuticals, metals, pesticides, and industrial contaminants) may impair fish physiology, potentially affecting phenotypic traits relevant for mate selection (e.g. pheromone production, courtship, and coloration). Although warming waters have led to documented range shifts, and chemical pollution is ubiquitous in freshwater ecosystems, few studies have tested hypotheses about how these stressors may facilitate hybridization and what this means for biodiversity and species conservation. Through a systematic literature review across disciplines (i.e. ecotoxicology and evolutionary biology), we evaluate the biological interactions, toxic mechanisms, and roles of physical and chemical environmental stressors (i.e. chemical pollution and climate change) in disrupting mate preferences and inducing interspecific hybridization in freshwater fish. Our study indicates that climate change-driven changes in water quality and chemical pollution may impact visual and chemical communication crucial for mate choice and thus could facilitate hybridization among fishes in freshwater ecosystems. To inform future studies and conservation management, we emphasize the importance of further research to identify the chemical and physical stressors affecting mate choice, understand the mechanisms behind these interactions, determine the concentrations at which they occur, and assess their impact on individuals, populations, species, and biological diversity in the Anthropocene.
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  • 文章类型: Journal Article
    分子杂交是药物发现和开发过程中广泛使用的策略,其由两种生物活性化合物向新实体的组合组成。在目前的研究中,两个来自倍半萜对应物双氢青蒿素和青蒿琥酸的杂合衍生物库,带有一系列单萜,合成并通过对原发性和转移性黑色素瘤细胞系的细胞活力测定进行评估。几乎所有获得的化合物都显示出微摩尔的抗黑素瘤活性和对该癌症转移形式的选择性。含有紫苏醇的四种杂化衍生物,香茅醇,nerol作为单萜的对应物成为该系列中最好的化合物,nerol与两种倍半萜结合时都有活性,双氢青蒿素和青蒿琥酸。对作用机理的初步研究表明,新合成的杂种的药理活性取决于碳和氧为中心的自由基的形成。这项研究表明,由于与单萜对应物的杂交,青蒿素半合成衍生物双氢青蒿素和青蒿琥酸的药效学作用具有正调节作用。
    Molecular hybridization is a widely used strategy in drug discovery and development processes that consists of the combination of two bioactive compounds toward a novel entity. In the current study, two libraries of hybrid derivatives coming from the linkage of sesquiterpene counterparts dihydroartemisinin and artesunic acid, with a series of monoterpenes, were synthesized and evaluated by cell viability assay on primary and metastatic melanoma cell lines. Almost all the obtained compounds showed micromolar antimelanoma activity and selectivity toward the metastatic form of this cancer. Four hybrid derivatives containing perillyl alcohol, citronellol, and nerol as monoterpene counterpart emerged as the best compounds of the series, with nerol being active in combination with both sesquiterpenes, dihydroartemisinin and artesunic acid. Preliminary studies on the mechanism of action have shown the dependence of the pharmacological activity of newly synthesized hybrids on the formation of carbon- and oxygen-centered radical species. This study demonstrated the positive modulation of the pharmacodynamic effect of artemisinin semisynthetic derivatives dihydroartemisinin and artesunic acid due to the hybridization with monoterpene counterparts.
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