Syntheses and antitumor activities of N′1,N′3-dialkyl-N′1,N′3-di-(alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

A series of N′¹,N′³-dialkyl-N′¹,N′³-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.     

Elevated oxidative damage is correlated with reduced fitness in interpopulation hybrids of a marine copepod

Aerobic energy production occurs via the oxidative phosphorylation pathway (OXPHOS), which is critically dependent on interactions between the 13 mitochondrial DNA (mtDNA)-encoded and approximately 70 nuclear-encoded protein subunits. Disruptive mutations in any component of OXPHOS can result in impaired ATP production and exacerbated oxidative stress; in mammalian systems, such mutations are associated with ageing as well as numerous diseases. Recent studies have suggested that oxidative stress plays a role in fitness trade-offs in life-history evolution and functional ecology. Here, we show that outcrossing between populations with divergent mtDNA can exacerbate cellular oxidative stress in hybrid offspring. In the copepod Tigriopus californicus, we found that hybrids that showed evidence of fitness breakdown (low fecundity) also exhibited elevated levels of oxidative damage to DNA, whereas those with no clear breakdown did not show significantly elevated damage. The extent of oxidative stress in hybrids appears to be dependent on the degree of genetic divergence between their respective parental populations, but this pattern requires further testing using multiple crosses at different levels of divergence. Given previous evidence in T. californicus that hybridization disrupts nuclear/mitochondrial interactions and reduces hybrid fitness, our results suggest that such negative intergenomic epistasis may also increase the production of damaging cellular oxidants; consequently, mtDNA evolution may play a significant role in generating postzygotic isolating barriers among diverging populations.     

Book review

Fucoid macroalgae are important primary producers and habitat modifiers on North Atlantic intertidal rocky shores. With decreasing latitude, western European fucoid populations display reduced levels of abundance, biomass and recruitment, while experiencing higher levels of physical environmental stress during summer months. We hypothesized that such reduction in the south is accompanied by a detectable decline in fucoid reproductive capacity. To test this hypothesis, morphological and reproductive traits of core (Welsh) and marginal (Portuguese) populations of two common fucoid species, Fucus vesiculosus and F. spiralis (Ochrophyta, Fucales), were examined. Morphological measurements showed that for a given thallus length, both fucoid species had smaller thallus volume and lower biomass in the southerly marginal part of the range. Significantly lower biomass of reproductive tissue of F. vesiculosus and a smaller number of receptacles per individual on specimens of both species indicate that levels of reproductive output are probably lower in southern populations. Despite the differences in reproductive traits observed between regions, reproductive effort (measured as the percentage of total dry biomass represented by reproductive tissue) of both species remained similar, as algae from both regions made similar investments in reproduction. The results indicate that stressful conditions reduced growth and number of receptacles of both species and amount of reproductive biomass of F. vesiculosus in the south but do not seem to change the way these algal species invest their energy. The decline in mass and reproductive biomass of specimens from southern shores found in this study, when combined with the lower abundance of adults and lower recruitment levels previously observed, is a strong indication of fucoid populations with lower levels of propagule output. This is an important factor when considering responses of these populations to a changing environment.     

Effects of light and hydrogen peroxide on gene expression of newly identified antioxidant enzymes in the harmful algal bloom species Chattonella marina

ABSTRACT

Antioxidant enzymes are essential proteins that maintain cell proliferation potential by protecting against oxidative stress. They are present in many organisms including harmful algal bloom (HAB) species. We previously identified the antioxidant enzyme 2-Cys peroxiredoxin (PRX) in the raphidophyte Chattonella marina. This enzyme specifically decomposes a hydrogen peroxide (H₂O₂). PRX is the only antioxidant enzyme so far identified in C. marina. This study used mRNA-seq, using Trinity assemble and blastx for annotation, to identify a further five antioxidant enzymes from C. marina: Cu Zn superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GPX), catalase (CAT), ascorbate peroxidase (APX) and thioredoxin (TRX). In the gene expression analysis of six enzymes (Cu/Zn-SOD, GPX, CAT, APX, TRX and PRX) using light-acclimated (100 μmol photons m^?2 s^?1) C. marina cells, only PRX gene expression levels were significantly increased by strong light irradiation (1000 μmol photons m^?2 s^?1). H₂O₂ concentration and scavenging activity were also increased and significantly positively correlated with PRX gene expression levels. In dark-acclimated cells, expression levels of all antioxidant enzymes except APX were significantly increased by light irradiation (100 μmol photons m^?2 s^?1). Expression decreased the following day, with the exception of PRX expression. With the exception of CAT, gene expression of antioxidant enzymes was not significantly induced by artificial H₂O₂ treatment, although average gene expression levels were slightly increased in some enzymes. Thus, we suggest that light is the main trigger of gene expression, but the resultant oxidative stress is also a possible factor affecting the gene expression of antioxidant enzymes in C. marina.     

Synthesis,antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes

A convenient synthetic route and the characterization of complexes trans-[PtCl₂(L)(PPh₃)] (L = Et₂NH (2), (PhCH₂)₂NH (3), (HOCH₂CH₂)₂NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration.     

Plant proteomics in India and Nepal: current status and challenges ahead

Plant proteomics has made tremendous contributions in understanding the complex processes of plant biology. Here, its current status in India and Nepal is discussed. Gel-based proteomics is predominantly utilized on crops and non-crops to analyze majorly abiotic (49 %) and biotic (18 %) stress, development (11 %) and post-translational modifications (7 %). Rice is the most explored system (36 %) with major focus on abiotic mainly dehydration (36 %) stress. In spite of expensive proteomics setup and scarcity of trained workforce, output in form of publications is encouraging. To boost plant proteomics in India and Nepal, researchers have discussed ground level issues among themselves and with the International Plant Proteomics Organization (INPPO) to act in priority on concerns like food security. Active collaboration may help in translating this knowledge to fruitful applications.     

环境因子对木棉种子萌发的影响

木棉(Bombax malabaricum DC.)是一种可以生长在干热河谷的落叶大乔木.河谷内,木棉成年树木生长良好,有大量结实,而其周围却很少有种苗出现.通过室内条件研究木棉种子的物理特性和萌发的生物学特性,可以了解该物种种子萌发对环境因子的需求,为探讨木棉在干热河谷内自然种群更新难和萌发阶段对这一特殊生境的适应性提供理论依据.经测定,木棉种子千粒重为39.08 g,比同科的其它物种要轻.四唑(TTC,1.O％)染色测定种子生活力的结果表明有生活力种子占64.0％.种皮对吸胀无障碍,种子在25℃吸胀2d时就开始萌发.检测了环境因子对种子萌发和幼苗生长的影响,结果表明,种子萌发对光照不敏感而且对温度有较广的适应性,15-35℃都可以萌发,25-35℃萌发率无显著差异,但随温度升高,萌发速率加快,幼苗长势增加;萌发过程对渗透胁迫敏感,聚乙二醇(PEG)浓度为0.10 g/mL时萌发率较对照显著下降,0.15 g/mL时种子就不能萌发;室温吸胀24h的种子对热激敏感,42℃热激2h后萌发率就已经显著下降;室湿下水杨酸(SA,1,10,100 mg/L)浸种24h,没有提高种子在萌发期间对干旱和热激的抗性.可见,高温和干旱是限制木棉种子成功萌发的关键因子,然而发现,温度较高时水分过大也会造成萌发后幼苗的死亡.     

黑河中游湿地景观破碎化过程及其驱动力分析

在遥感和GIS技术支持下,基于1975-2010年长时间序列遥感影像,选取斑块密度指数(PD)、景观内部生境面积指数(IA)、斑块平均面积指数(MPS)、斑块形状破碎化指数(FS1、FS2)等具有典型生态意义的景观指数模型,系统分析了黑河中游湿地景观的破碎化过程,并结合灰色关联分析、主成分分析等方法,探讨了影响研究区湿地景观破碎化过程的各驱动因子.结果表明:近35年来,研究区湿地景观破碎化主要表现为斑块平均面积的萎缩,斑块密度的上升以及斑块形状破碎化指数的增大.整个研究时段内,研究区湿地斑块平均面积减少了48.95hm2,斑块密度的上升0.006个/hm2;导致黑河中游湿地景观破碎化发生和发展的驱动力包含自然和人文两个方面.自然因子对湿地景观破碎化进程的影响则主要体现在气温和降水上,而且气温对湿地景观破碎化进程的影响程度明显大于降水.但在1975-2010年间的这一较小时间尺度上,人类活动对湿地景观破碎化的贡献率明显高于自然因子,人类活动能力的增强以及影响范围的不断扩大是引发黑河中游湿地景观破碎化的主因.