流域尺度水土保持生物措施减沙效益研究

1　引　　言黄土高原位于黄河中游 ,流经黄土高原的 9大支流进入河口镇至花园口的中游河段 ,总径流量为 187× 10 8ｍ3 ,输沙量占黄河流域总沙量的 90 % .建国以来以修建梯田坝地、造林种草、建谷坊、调整种植结构为主的水土保持工程、生物治理长年不懈 ,其目的在于减水减沙 ,改善流域生态环境 .但是 ,除部分中小尺度流域进入生态、经济效益良性循环的轨道外 ,大部分地区生态环境仍然十分脆弱 ,部分地区有恶化之势 .因此 ,定量评价水土保持工程、生物措施的治理效益是广为关注的研究课题 ,虽相关的研究成果不少 ,但是绝大部分工作是评价水土…     

The insulin paradox: aging, proteotoxicity and neurodegeneration

Distinct human neurodegenerative diseases share remarkably similar temporal emergence patterns, even though different toxic proteins are involved in their onset. Typically, familial neurodegenerative diseases emerge during the fifth decade of life, whereas sporadic cases do not exhibit symptoms earlier than the seventh decade. Recently, mechanistic links between the aging process and toxic protein aggregation, a common hallmark of neurodegenerative diseases, have been revealed. The insulin/insulin-like growth factor 1 (IGF1) signalling pathway - a lifespan, metabolism and stress-resistance regulator - links neurodegeneration to the aging process. Thus, although a reduction of insulin signalling can result in diabetes, its reduction can also increase longevity and delay the onset of protein-aggregation-mediated toxicity. Here we review this apparent paradox and delineate the therapeutic potential of manipulating the insulin/IGF1 signalling pathway for the treatment of neurodegenerative diseases.     

Arthropod food webs become increasingly lipid‐limited at higher trophic levels

Understanding why food chains are relatively short in length has been an area of research and debate for decades. We tested if progressive changes in the nutritional content of arthropods with trophic position limit the availability of a key nutrient, lipid, for carnivores. Arthropods at higher trophic levels had progressively less lipid and more protein in their bodies compared with arthropods at lower trophic levels. The nutrients present in arthropod bodies were directly related to the nutrients that predators extracted when feeding on those arthropods. As a consequence, nutrient assimilation shifted from lipid‐biased to protein‐biased as arthropods ascended trophic levels from herbivores to secondary carnivores. Successive changes in the nutritional consequences of predation may ultimately set an upper limit on the number of trophic levels in arthropod communities. Further work is needed to examine the influence of lipid and other nutrients on food web traits in a range of ecosystems.     

Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila

Parkinson's disease is a common neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of the protein alpha-synuclein into aggregates called Lewy bodies and Lewy neurites. Parkinson's disease can be modeled in Drosophila where directed expression of alpha-synuclein induces compromise of dopaminergic neurons and the formation of Lewy body-like aggregates. The molecular chaperone Hsp70 protects cells from the deleterious effects of alpha-synuclein, indicating a potential therapeutic approach to enhance neuron survival in Parkinson's disease. We have now investigated the molecular mechanisms by which the drug geldanamycin protects neurons against alpha-synuclein toxicity. Our studies show that geldanamycin sensitizes the stress response within normal physiological parameters to enhance chaperone activation, offering protection against alpha-synuclein neurotoxicity. Further, geldanamycin uncouples neuronal toxicity from Lewy body and Lewy neurite formation such that dopaminergic neurons are protected from the effects of alpha-synuclein expression despite the continued presence of (and even increase in) inclusion pathology. These studies indicate that compounds that modulate the stress response are a promising approach to treat Parkinson's disease.     

Increased Protein Oxidation in Human Substantia Nigra Pars Compacta in Comparison with Basal Ganglia and Prefrontal Cortex Measured with an Improved Dinitrophenylhydrazine Assay

Abstract: The dopaminergic phenotype of neurons in human substantia nigra deteriorates during normal aging, and loss of these neurons is prominent in Parkinson's disease. These degenerative processes are hypothesized to involve oxidative stress. To compare oxidative stress in the nigra and related regions, we measured carbonyl modifications of soluble proteins in postmortem samples of substantia nigra, basal ganglia, and prefrontal cortex from neurologically normal subjects, using an improved 2,4-dinitrophenylhydrazine assay. The protein carbonyl content was found to be about twofold higher in substantia nigra pars compacta than in the other regions. To further analyze this oxidative damage, the distribution of carbonyl groups on soluble proteins was determined by western immunoblot analysis. This method revealed that carbonyl content of the major proteins in each region was linearly dependent on molecular weight. This distribution raises the possibility that protein carbonyl content is controlled by a size-dependent mechanism in vivo. Our results suggest that oxidative stress is elevated in human substantia nigra pars compacta in comparison with other regions and that oxidative damage is higher within the dopaminergic neurons. Elevated oxidative damage may contribute to the degeneration of nigral dopaminergic neurons in aging and in Parkinson's disease.     

Quinoprotein Adducts Accumulate in the Substantia Nigra of Aged Rats and Correlate with Dopamine-Induced Toxicity in SH-SY5Y Cells

Parkinson’s disease (PD) is an age-dependent neurodegenerative disorder characterized by dopaminergic neuron loss in substantia nigra. Previous studies have implicated a role of dopamine oxidation in PD. Dopamine oxidation leads to the formation of dopamine quinone, which generates reactive oxygen species and covalently modifies cysteinyl proteins to form quinoprotein adduct. We compared quinoprotein adduct formation and lipid peroxidation in different brain regions of young and old rats. We found a prominent age-dependent accumulation of quinoprotein adducts in the substantia nigra, while no significant change of lipid peroxidation was detected in any brain regions of 2- to 15-month old rats. To determine whether quinoprotein adduct formation correlates with dopamine-induced cytotoxicity, we analyzed dopamine treated SH-SY5Y cells and found a strong correlation between quinoprotein adduct formation and cytotoxicity. Together, our results indicate that quinoprotein adduct formation may play a role in the age-dependent selective vulnerability of dopaminergic neurons in PD.     

Is malfunction of the ubiquitin proteasome system the primary cause of alpha-synucleinopathies and other chronic human neurodegenerative disease?

Neuropathological investigations have identified major hallmarks of chronic neurodegenerative disease. These include protein aggregates called Lewy bodies in dementia with Lewy bodies and Parkinson's disease. Mutations in the alpha-synuclein gene have been found in familial disease and this has led to intense focused research in vitro and in transgenic animals to mimic and understand Parkinson's disease. A decade of transgenesis has lead to overexpression of wild type and mutated alpha-synuclein, but without faithful reproduction of human neuropathology and movement disorder. In particular, widespread regional neuronal cell death in the substantia nigra associated with human disease has not been described. The intraneuronal protein aggregates (inclusions) in all of the human chronic neurodegenerative diseases contain ubiquitylated proteins. There could be several reasons for the accumulation of ubiquitylated proteins, including malfunction of the ubiquitin proteasome system (UPS). This hypothesis has been genetically tested in mice by conditional deletion of a proteasomal regulatory ATPase gene. The consequences of gene ablation in the forebrain include extensive neuronal death and the production of Lewy-like bodies containing ubiquitylated proteins as in dementia with Lewy bodies. Gene deletion in catecholaminergic neurons, including in the substantia nigra, recapitulates the neuropathology of Parkinson's disease.     

Immunocytochemical Quantification of Tyrosine Hydroxylase at a Cellular Level in the Mesencephalon of Control Subjects and Patients with Parkinson's and Alzheimer's Disease

Abstract: Parkinson's disease is characterized by massive degeneration of the melanized dopaminergic neurons in the substantia nigra. The functional capacity of the surviving nigral neurons is affected, as indicated by the subnormal levels of tyrosine hydroxylase (TH) mRNA in these neurons and the presence in the parkinsonian mesencephalon of melanized neurons lacking TH immunoreactivity. This is apparently in contradiction with the known overactivity of dopamine synthesis and release that occurs in the remaining dopaminergic terminals. To test the ability of the surviving neurons to express TH protein, a semiquantitative immunocytochemical method was developed. The relative amounts of TH were estimated with a computer-assisted image analysis system in the dopaminergic neurons of representative mesencephalic sections of control and parkinsonian brains and for comparison in brains from patients with Alzheimer's disease. In control brains, the mean TH content per neuron differed from one subject to another and between the different dopaminergic cell groups of the mesencephalon in the same subject. Within a given dopaminergic region, the level of TH was variable among neurons. In patients with Parkinson's disease, the ratio of TH protein content per neuron in the substantia nigra by reference to that of the central gray substance was reduced. In patients with Alzheimer's disease, the amount of TH was selectively reduced in the remaining dopaminergic neurons of the ventral tegmental area, a region characterized by a loss in dopaminergic neurons. The decrease in cellular TH content might therefore be related to the presence of the neurodegenerative process in the area considered. In patients with Parkinson's disease, the incapacity of the surviving neurons to express normal TH levels may reduce the efficiency of the hyperactivity mechanisms that develop in the remaining striatal dopaminergic terminals.     

Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease affecting thousands of people in the world and effective treatment is still not available. Over two decades of intense research using AD postmortem brains, transgenic mouse and cell models of amyloid precursor protein and tau revealed that amyloid beta (Aβ) and hyperphosphorylated tau are synergistically involved in triggering disease progression. Accumulating evidence also revealed that aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction initiate and contributes to the development and progression of the disease. The purpose of this article is to summarize the latest progress in aging and AD, with a special emphasis on the mitochondria, oxidative DNA damage including methods of its measurement. It also discusses the therapeutic approaches against oxidative DNA damage and treatment strategies in AD.     

Drp1的调控对PINK1突变转基因果蝇的保护作用

帕金森病（PD）是以黑质致密部多巴胺神经元选择性减少和胞浆内路易小体的形成为特征的神经退行性疾病。研究发现,PTEN诱导激酶1(PINK1)基因突变导致家族性早发型帕金森病的发生。在转基因果蝇中,PINK1功能丢失导致间接飞行肌缺陷,线粒体结构、功能障碍,多巴胺神经元丢失。本研究在PINK1突变PD转基因果蝇中,进行发动蛋白相关蛋白1（Drp1）过表达和敲低,探索Drp1对PD转基因果蝇的保护作用及其可能机制。本研究选用MHC-Gal4/UAS系统的PD转基因果蝇模型,特异性启动PINK1B9基因于果蝇肌肉组织中表达;运用Drp1基因过表达和RNA干扰干预PINK1B9转基因果蝇,研究其对PD转基因果蝇的作用。结果显示,不论过表达Drp1还是Drp1敲低均可挽救PINK1突变转基因果蝇,降低翅膀异常率,改善飞行能力,恢复间接飞行肌排列,调节线粒体形态,提高ATP生成量,上调NDUFS3蛋白表达水平。本文结果提示,Drp1的调控挽救PINK1突变转基因果蝇与线粒体呼吸链有关。     

Ultrastructure and Lipase Activity of Cotyledon cell During Pod Development in Peanut

A series of significant changes of the ultrastructure and lipase activity of cotyledon cell were found in peanut (Arachis hypogaea) during pod development. In he initial stage of cotyledon development there were many plastids which kept producing starch grain and there were low lipase activity and very few lipid and protein bodies in the cell. In the middle stage of cotyledon development, a great number of larger lipid bodies were seen in the cell and a lot of protein bodies formed in the vacuoles and continued to increase in size. Lipase activity increased in the cytoplasm, endoplasmic reticulum, protein bodies, plasmalemma and intercellular space. In the later stage of cotyledon development, the lipid bodies did not increase in number but became slightly larger. The protein bodies continued to increase both in number and in size. Lipase acttvity was even hegher in the cytoplasm. In the final stage the protein bodies became irregular in shape and some of them tended to disintegrate with their content entered into the space around the lipid bodies. The lipase activity in the cell declined. The results indicated that the lipid body originated in the cytoplasm and the protein body originated in the vacuole; that the accumulation of oil and protein in peanut cotyledon resulted from the formation and development of lipid and protein bodies in the cell, and that the changes of plasmid and lipase activity in the cell played a role in the development of lipid body during the development of cotyledon.     

Notes on the life-history and ecology of Tachypodoiulus niger (Diplopoda, Iulidae) in Britain

In some iulids females can moult several times after first attaining maturity but males cannot. Males of Tachypodoiulus niger (Leach) are exceptional in that they can moult, but they lose their functional intromittent organs in the process, regaining them after a second moult. The process can be repeated, a series of functional males alternating with nonfunctional males. This extension of the life and the consequent increase in number of segments led Verhoeff (1928) to postulate that the ancestral millipede was short-bodied and that many-segmented forms were derived from it. We think that this extension of life is of ecological rather than phylogenetic significance–adapting the species to disperse widely to scattered habitats. In particular, the extension of life of males as well as of females may ensure a reasonable sex ratio in those areas where the species is least dense.
In Britain, Tachypodoiulus niger lays eggs in spring which reach the fourth and fifth stadia by their first winter and the seventh, eighth and ninth stadia by their second winter. Maturity is usually attained by males in the eighth stadium but occasional specimens mature at stadium seven and others defer maturity until the ninth. Both sexes can proceed to the fourteenth stadium but adults in Britain usually belong to two generations of two and three years old, divided mainly between the eighth, ninth and tenth stadia. Details are given of a large collection made by the late Dr Scott of animals taking refuge in his house at Henley-on-Thames. Animals in Britain appear to have a similar life history to those in Germany as described by Verhoeff, but effective comparison has depended on correcting and re-interpreting some of Verhoeff's data.     

Harpagoside attenuates MPTP/MPP⁺ induced dopaminergic neurodegeneration and movement disorder via elevating glial cell line-derived neurotrophic factor

Parkinson's disease is a chronic neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. New therapeutic approaches aiming at delaying or reversing the neurodegenerative process are under active investigations. In this work, we found that harpagoside, an iridoid purified from the Chinese medicinal herb Scrophularia ningpoensis, could not only prevent but also rescue the dopaminergic neurodegeneration in MPTP/MPP(+) intoxication with promising efficacy. Firstly, in cultured mesencephalic neurons, harpagoside significantly attenuated the loss of TH-positive neuron numbers and the shortening of axonal length. Secondly, in a chronic MPTP mouse model, harpagoside dose-dependently improved the loco-motor ability (rotarod test), increased the TH-positive neuron numbers in the substantia nigra pars compacta (unbiased stereological counting) and increased the striatal DAT density ((125) I-FP-CIT autoradiography). Thirdly, harpagoside markedly elevated the GDNF mRNA and GDNF protein levels in MPTP/MPP(+) lesioned models. However, the protecting effect of harpagoside on the dopaminergic degeneration disappeared when the intrinsic GDNF action was blocked by either the Ret inhibitor PP1 or the neutralizing anti-GDNF antibody. Taken together, we conclude that harpagoside attenuates the dopaminergic neurodegeneration and movement disorder mainly through elevating glial cell line-derived neurotrophic factor.     

花生荚果发育过程中子叶细胞的超微结构和脂酶活性的研究

在花生(Arachis hypogaea)荚果发育过程中,子叶细胞的超微结构和脂酶活性皆发生了显著变化。子叶生长初期,缅胞中质体较多,并不断形成淀粉粒;脂酶活性低,脂体和蛋白体很少。子叶发育中期,子叶细胞质中出现大量体积较大的脂体,液泡中的蛋白体不断形成和增大,而且细胞质、内质网、蛋白体外膜、细胞质膜和细胞间隙上皆显示较强的脂酶活性。子叶发育后期,脂体数量不再增加,但体积略有增大,间质透明度也有提高;蛋白体增大较小,但数量却进一步增多;细胞质中仍显示较强的脂酶活性。至末期时,蛋白体形态变得不规则,甚至出现部分解体,其基质充挤脂体间隙;细咆中的脂酶活性减弱。研究表明,花生脂体起源于细胞质,蛋白体起源于液泡,子叶油分和蛋白质的积累足体内脂体和蛋白体不断发育的结果,细胞中脂酶活性的变化可能与脂体发育有关。     

Long-Term Induction of Tyrosine Hydroxylase Expression: Compensatory Response to Partial Degeneration of the Dopaminergic Nigrostriatal System in the Rat Brain

Abstract: The present study was undertaken to examine the adaptive changes occurring 1 and 6 months after moderate or severe unilateral 6-hydroxydopamine-induced lesions confined to the lateral part of the rat substantia nigra pars compacta (SNC). The expression of tyrosine hydroxylase (TH) enzyme was analyzed in the remaining dopaminergic nigral cell bodies and in the corresponding striatal nerve endings. In the cell bodies of the lesioned SNC, TH mRNA content was increased (+20 to +30%) 6 months after the lesion without changes in cellular TH protein amounts. The depletion of TH protein in the nerve terminal area was less severe than the percentage of cell loss observed in the SNC at 1- and 6-month postlesion intervals. Moreover, the decrease in TH protein in the ipsilateral striatum was less pronounced 6 months after lesion than 1 month after. That no corresponding change in TH protein content was observed in the cell bodies at a time when TH increased in nerve terminals suggests that the newly synthesized protein is probably rapidly transported to the striatal fibers. These results suggest the existence of a sequence of changes in TH expression between cell bodies and fibers, occurring spontaneously after partial denervation of the nigrostriatal pathway.     

A deadly spread: cellular mechanisms of α-synuclein transfer

Classically, Parkinson's disease (PD) is linked to dopamine neuron death in the substantia nigra pars compacta. Intracytoplasmic protein inclusions named Lewy bodies, and corresponding Lewy neurites found in neuronal processes, are also key features of the degenerative process in the substantia nigra. The molecular mechanisms by which substantia nigra dopamine neurons die and whether the Lewy pathology is directly involved in the cell death pathway are open questions. More recently, it has become apparent that Lewy pathology gradually involves greater parts of the PD brain and is widespread in late stages. In this review, we first discuss the role of misfolded α-synuclein protein, which is the main constituent of Lewy bodies, in the pathogenesis of PD. We then describe recent evidence that α-synuclein might transfer between cells in PD brains. We discuss in detail the possible molecular mechanisms underlying the proposed propagation and the likely consequences for cells that take up α-synuclein. Finally, we focus on aspects of the pathogenic process that could be targeted with new pharmaceutical therapies or used to develop biomarkers for early PD detection.     

Cucullanus costaricensis n. sp. (Nematoda: Cucullanidae), a parasite of Bagre pinnimaculatus (Siluriformes: Ariidae) from Río Tempisque, Costa Rica

A new species of nematode, Cucullanus costaricensis n. sp., is described from the Red Sea catfish Bagre pinnimaculatus from Río Tempisque, Costa Rica. The new species is characterized by the following traits: spicules and gubernaculum length (0.48 +/- 0.02 [0.45-0.50] and 0.20 +/- 0.02 [0.18-0.21], respectively); a protruding cloacal region in males, and the arrangement of caudal papillae (1 medial unpaired precloacal papilla and 10 pairs of papillae: 3 precloacals [first pair subventral and anterior to ventral sucker; second and third pairs posterior to ventral sucker; second pair asymmetric and subventral; third pair slightly subventral and closer to cloacal opening], 3 subventral adcloacal pairs [pairs 4-6], and 4 pairs of postcloacal papillae [seventh pair lateral, eighth pair subdorsal, ninth and tenth pairs subventral]); and lateral phasmids between the seventh and eighth pairs of postcloacal papillae. This finding represents the first record for a species of Cucullanus in Central America.     

Elevated oxidative stress in models of normal brain aging and Alzheimer's disease

Age-associated neurodegenerative disorders are becoming more prevalent as the mean age of the population increases in the United States over the next few decades. Both normal brain aging and Alzheimer's disease (AD) are associated with oxidative stress. Our laboratory has used a wide variety of physical and biochemical methods to investigate free radical oxidative stress in several models of aging and AD. Beta-amyloid (A beta), the peptide that constitutes the central core of senile plaques in AD brain, is associated with free radical oxidative stress and is toxic to neurons. This review summarizes some of our studies in aging and A beta-associated free radical oxidative stress and on the modulating effects of free radical scavengers on neocortical synaptosomal membrane damage found in aging and A beta-treated systems.     

Glial cell line-derived neurotrophic factor alters lipid composition and protein distribution in MPP+-injured differentiated SH-SY5Y cells

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and striatum. Glial cell line-derived neurotrophic factor (GDNF) can effectively promote the differentiation and survival of many types of neurons, especially dopaminergic neurons, suggesting it could be a treatment for PD. Lipid rafts are highly dynamic cell membrane domains that contain numerous signal protein receptors, providing an important platform for signal transduction. Compelling evidence indicates that alterations in lipid rafts are associated with PD, and some studies have reported that GDNF can regulate the expression of caveolin-1, a lipid raft-marker protein. However, the precise effects of GDNF on lipid rafts remain unknown. We developed a cellular PD model, purified detergent-resistant membranes (membrane rafts), and performed proteomic and lipid metabolomics analyses to examine changes in lipid rafts after GDNF treatment. The results showed considerable protein and lipid alterations in response to GDNF, especially altered levels of dopamine-β-hydroxylase, heat shock 70 kDa protein, neural cell adhesion molecule, cytoskeletal proteins, and long-chain polysaturated/unsaturated fatty acids. These findings reveal a new avenue to explore the relationships between GDNF, lipid rafts, and PD and support the hypothesis that GDNF may be a useful treatment for PD.