Eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells

Background: Gene therapy has attracted attention for its potential to specifically and efficiently target cancer cells with minimal toxicity to normal cells. At present, it offers a promising direction for the treatment of cancer patients. Numerous vectors have been engineered for the sole purpose of killing cancer cells, and some have successfully suppressed malignant tumours. Many plant proteins have anticancer properties; consequently, genes encoding some of these proteins are being used to design constructs for the inhibition of multiplying cancer cells. Results: Data addressing the function of vectors harbouring genes specifically encoding ricin, saporin, lunasin, linamarase, and tomato thymidine kinase 1 under the control of different promoters are summarised here. Constructs employing genes to encode cytotoxic proteins as well as constructs employing genes of enzymes that convert a nontoxic prodrug into a toxic drug are considered here. Conclusion: Generation of eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells may permit the broadening of cancer gene therapy strategy, particularly because of the specific mode of action of anticancer plant proteins.     

The archaeology of Australia's tropical rainforests

Archaeological research in the Australia's northeast Queensland rainforest and margins has revealed a human antiquity of at least 8000 cal year BP within the rainforest and at least 30,000 years on the western edge. Rainforest occupation before 2000 cal year BP was at generally very low levels, after which time settlement of this environment became intensive and probably permanent. Exploitation of toxic varieties of nuts began about 2500 cal year BP, peaking after 1500 cal year BP. This economic development appears crucial to successful human adaptation to rainforests in the area and was pivotal in facilitating the long-term permanent human settlement of the wet tropics. The role of fire, El Niño Southern Oscillation (ENSO) activity and shifting vegetation regimes were important catalysts in providing opportunities for permanent Australian rainforest Aboriginal occupation. The results have implications for global understandings of rainforest occupation by modern people. It demonstrates the wide temporal and spatial variability of human rainforest colonization processes worldwide.     

Toxic and trace metal concentrations in liver and kidney of dogs: influence of diet, sex, age, and pathological lesions

The aim of this study was to provide data on the main toxic and trace metals in the liver and kidney of domestic dogs in Galicia, NW Spain and to evaluate the influence of diet, sex, age, and pathological lesions on metal accumulation. Samples of the liver and kidney from 77 male and female dogs, aged between 6 mo and 18 yr, were collected during ordinary necropsy. Samples were acid-digested and metal concentrations determined by inductively coupled plasma (ICP)-mass spectrometry and ICP-atomic emission spectrometry. Mean toxic metal concentrations (geometric means for liver and kidney respectively) were 11.5 and 15.8 μg/kg wet weight for As, 56.3 and 166 μg/kg for Cd, 32.7 and 51.9 μg/kg for Hg, and 60.1 and 23.6 μg/kg for Pb. For the trace metals, these concentrations were respectively 16.3 and 21.0 μg/kg for Co, 57.6 and 43.9 μg/kg for Cr, 42.1 and 5.95 mg/kg for Cu, 394 mg/kg and 95.7 mg/kg for Fe, 2.39 and 0.956 mg/kg for Mn, 0.522 and 0.357 mg/kg for Mo, 23.8 and 26.8 μg/kg for Ni, 0.686 and 1.39 mg/kg for Se, and 46.7 and 26.0 mg/kg for Zn. Cd concentrations in the kidney significantly increased with age, and Co concentrations in the liver and kidney significantly decreased with age. Hepatic Pb concentrations were significantly higher in growing (<1 yr) and old (>10 yr) dogs. Animals with pathological lesions showed significantly higher Co and lower Mn and Zn concentrations in liver than animals with-out macroscopic abnormalities. Dogs that received commercial diets in general showed low variability in hepatic mineral status compared to animals that receive homemade feeds or a mixture of commercial and homemade feeds.     

Brain Iron Toxicity: Differential Responses of Astrocytes,Neurons, and Endothelial Cells

Iron accumulation or iron overload in brain is commonly associated with neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases, and also plays a role in cellular damage following hemorrhagic stroke and traumatic brain injury. Despite the brain’s highly regulated system for iron utilization and metabolism, these disorders often present following disruptions within iron metabolic pathways. Such dysregulation allows saturation of proteins involved in iron transport and storage, and may cause an increase in free ferrous iron within brain leading to oxidative damage. Not only do astrocytes, neurons, and brain endothelial cells serve unique purposes within the brain, but their individual cell types are equipped with distinct protective mechanisms against iron-induced injury. This review evaluates iron metabolism within the brain under homeostatic and pathological conditions and focuses on the mechanism(s) of brain cellular iron toxicity and differential responses of astrocytes, neurons, and brain vascular endothelial cells to excessive free iron. Special issue dedicated to Dr. Moussa Youdim. An erratum to this article can be found at     

硝酸盐还原促进毒害性有机污染物降解的研究进展

大量具有高毒性、持久性和生物蓄积性的有机污染物被排放到环境中,对生态环境和人类健康造成了严重威胁。近年来,利用硝酸盐作电子受体在厌氧条件下降解毒害性有机污染物,已取得一定的进展。本文综述了硝酸盐还原体系中几种典型毒害性有机污染物(多环芳烃、单环或杂环芳烃类有机物及卤代有机物)的厌氧降解研究进展。在此基础上,提出了硝酸盐还原促进毒害性有机污染物降解研究中存在的主要问题及其在加速污染环境净化方面的应用前景。     

Investigation of the Effects of Some Phenolic Compounds on the Activities of Glucose‐6‐Phosphate Dehydrogenase and 6‐Phosphogluconate Dehydrogenase from Human Erythrocytes

Polyphenols are the important compounds that have various bioactivities. They constitute vital active agents of not only daily diet but also natural medicines that are used traditionally. It is generally considered that they are safe because they are natural. In some conducted studies, different negative effects of these compounds were mentioned. Twelve phenolic compounds have been assayed to determine the effect of inhibition on glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro studies, the enzymes were purified from human erythrocytes using 2′,5′‐ADP Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid, ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin, only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect. Chlorogenic acid, p‐coumaric acid, and syringic acid did not exhibit an effect on the activity of the two enzymes.     

Toxic and essential elements in children's blood (<6 years) from Kinshasa,DRC (the Democratic Republic of Congo)

In this study we determined the concentration of 9 trace elements (As, Cd, Cu, Hg, Mn, Mo, Pb, Se and Zn) in whole blood of children (n = 100, 64 girls, 36 boys and median age: 36 months) using inductively coupled plasma mass spectrometry (ICP-MS). The proportion of children potentially deficient in essential elements or poisoned by toxic elements was evaluated. The aging effects on the concentration of these elements were also investigated. The median values were 3.17 μg/L (As), 0.15 μg/L (Cd), 1.1 mg/L (Cu), 2.1 μg/L (Hg), 10.4 μg/L (Mn), 17.7 μg/L (Mo), 8.7 μg/dL (Pb), 10.7 μg/L (Se) and 5.0 mg/L (Zn). The concentration of many elements (As, Cd, Hg, Mn, Pb and Zn) showed significant age variations but not sex influence. Regarding levels of the essential elements (Cu, Mn, Mo, Se and Zn), B-Cu, B-Mn, B-Se and B-Zn were in the normal range, whereas exceeded levels were observed for B-Mo. None of these children was deficient in essential elements. Except B-Cd, all toxic elements showed exceeded blood levels. The proportion of children potentially poisoned by toxic elements varies from 10% (n = 10) to 95% (n = 95) and depends on toxic element: 95% for As, 10% for Hg and 35% for Pb. The main health concerns emerging from this study are the high As, Hg and Pb exposures of the Kinshasan children requiring further documentation, corrective actions and the implementation of appropriate regulations.     

The global distributional patterns of toxic, bloom dinoflagellates recorded from the Eurasian Arctic

The global distributional patterns are presented for 14 toxic and potentially toxic dinoflagellate species (PSP, DSP, yessotoxin, azaspiracid and their analogues, ichthyotoxic and haemolytic compound producers) recorded from the Eurasian Arctic and which have caused harmful blooms elsewhere. The distributional patterns are based on materials collected during 28 expeditions to the Eurasian Arctic during the period from 1976 to 1999 (1810 samples from 539 stations) and about 500 literary sources. All Russian literature on the occurrences of dinoflagellates in the Eurasian Arctic was analyzed and relevant references are given.     

Noncooperative cadmium(II) binding to human metallothionein 1a

The two-domain (βα) mammalian metallothionein binds seven divalent metals, however, the binding mechanism is not well characterized and recent reports require the presence of the partially metallated protein. In this paper, step-wise metallation of the metal-free, two-domain βα-rhMT and the isolated β-rhMT using Cd(II) is shown to proceed in a noncooperative manner by analysis of electrospray ionization mass spectrometric data. Under limiting amounts of Cd(II), all intermediate metallation states up to the fully metallated Cd₃-β-rhMT and Cd₇-βα-rhMT were observed. Addition of excess Cd(II), resulted in formation of the supermetallated (metallation in excess of normal levels) Cd₄-β- and Cd₈-βα-metallothionein species. These data establish that noncooperative cadmium metallation is a property of each isolated domain and the complete two-domain protein. Our data now also establish that supermetallation is a property that may provide information about the mechanism of metal transfer to other proteins.     

Highlights of large lake research and management in Europe

Lakes in Europe have a bipolar distribution by latitude with higher lake densities in the north (58–65° N) and south (38–48° N). By area, 95% of the large lakes (>100 km²) are located at altitudes lower than 100 m above sea level (ASL) and only 1% lie higher than 1,000 m ASL. Physically large lakes exhibit several similarities to seas and oceans in their thermal structure and circulation dynamics. From the chemical point of view, lakes are important accumulation sites for substances transported from the watershed or built up in the lake itself but they may contribute positively to global greenhouse gas emission. Fauna and flora of ancient large lakes such as the Caspian Sea and Lake Ohrid include large numbers of endemic species, which become endangered if conditions change because of direct human impact, alien species invasions or climate change. Large lakes offer a wide range of ecosystem services to society, the multiple use of which creates multiple pressures on these water bodies such as nutrient load and toxic pollution, modification of hydrology and shore line structure, and shifting of the food web balance by stocking or harvesting various species. Although large lakes are among the best-studied ecosystems in the world, the application to them of environmental regulations such as the European Water Framework Directive is a challenging task and requires that several natural and management aspects specific to these water bodies are adequately considered.