Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] Prevents 6-Hydroxydopamine-induced Dopamine Depression in Mouse Striatum and Increases Superoxide Scavenging Activity in Serum

As superoxide (·O₂^–) and hydroxyl radical (·OH) have been implicated in pathogenesis of Parkinsons disease, free radical scavenging, antioxidant, and neuroprotective agents have attracted attention as ways to prevent progression. We examined effects of zingerone, an alkaloid extracted from ginger root, on 6-hydroxydopamine (6-OHDA)-induced dopamine (DA) reduction in mouse striatum. Zingerone administration 1 h before and for 6 more days following one intracerebroventricular 6-OHDA injection prevented reductions of striatal DA and its metabolites, and increased serum ·O₂^– scavenging activity. Zingerone did not change activities of catalase or glutathione peroxidase in striatum or serum, or ·O₂^– scavenging activity in striatum. Treatment with diethyldithiocarbamate, SOD inhibitor, abolished the protective effect of zingerone against 6-OHDA-induced DA reduction. In vitro, zingerone scavenged ·O₂^– and ·OH and suppressed lipid peroxidation only weakly. Thus, direct antioxidant effects may be a minor component of its putative neuroprotective effect; instead, zingerone acted mainly by increasing systemic superoxide dismutase activity. Effects of zingerone treatment in this model suggest possible value in treatment of Parkinsons disease.     

Afferent bursting activity of ruff lateral line induced by background noise stimulation

Summary Single unit resting activities were recorded from fibres innervating a neuromast of the supra-orbital canal of the lateral line system of the ruff (Acerina cernua). The interval histogram of 1 of the 4 types of resting activity had a bimodal distribution (bursting activity). The resting activity of these fibres was compared with the measured vibration of the experimental table. The conclusion that the bursting activity is not spontaneous but is caused by small background vibrations of the table was supported by recording of extracellular hair cell responses.Abbreviation ISI Interspike interval     

Gene therapy in Parkinson’s disease

Gene therapy in Parkinsons disease appears to be at the brink of the clinical study phase. Future gene therapy protocols will be based on a substantial amount of preclinical data regarding the use of ex vivo and in vivo genetic modifications with the help of viral or non-viral vectors. To date, the supplementation of neurotrophic factors and substitution for the dopaminergic deficit have formed the focus of trials to achieve relief in animal models of Parkinsons disease. Newer approaches include attempts to influence detrimental cell signalling pathways and to inhibit overactive basal ganglia structures. Nevertheless, current models of Parkinsons disease do not mirror all aspects of the human disease, and important issues with respect to long-term protein expression, choice of target structures and transgenes and safety remain to be solved. Here, we thoroughly review available animal data of gene transfer in models of Parkinsons disease.     

The role of synphilin-1 in synaptic function and protein degradation

The name synphilin-1 comes from its identification as an alpha-synuclein-interacting protein (SNCAIP) in yeast two-hybrid screens. Since alpha-synuclein (PARK1) was the first gene identified as causing inherited forms of Parkinsons disease (PD), synphilin-1 was quickly implicated in neurodegeneration in PD. Recently, the first genetic evidence for the direct contribution of synphilin-1 in the pathogenesis of PD has been defined with the identification of an R621C mutation as a susceptibility factor for PD in two German patients. Extensive in vitro studies have determined the physiological functions of synphilin-1, identified novel synphilin-1-interacting proteins, and linked synphilin-1 to ubiquitin-mediated protein degradation. The present article provides an overview of the current concepts of the role of synphilin-1 in synaptic function and protein degradation and in the molecular mechanisms leading to neurodegeneration in PD.The work of R.K. on synphilin-1 is supported by a grant from the Fritz Thyssen Foundation, a grant from the Federal Ministry of Education and Research (Fö 01KS9602), and the Interdisciplinary Center of Clinical Research Tübingen (IZKF)     

Synucleins and their relationship to Parkinson’s disease

Parkinsons disease (PD) is one of the most common neurodegenerative motor disorders, marked by chronic progressive loss of neurons in the substantia nigra. It has long been believed that PD is caused by environmental factors. The discovery of genetic factors involved in PD has improved the understanding of the pathology of the disease. The first gene found to be mutated in PD encodes for the presynaptic protein -synuclein. -Synuclein is a major component of Lewy bodies and Lewy neurites, which represent the morphological hallmarks of the disease. The mechanisms by which -synuclein is involved in nigral cell death remain poorly understood. Moreover, the factors triggering the formation of -synuclein-positive inclusion bodies remain enigmatic. Indeed, even the normal cellular functions of -synuclein and of the other synucleins (-synuclein and -synuclein) are still unknown. Several lines of evidence suggest that they play a role in the regulation of vesicular turnover under normal nonpathological conditions.The work of O. von Bohlen und Halbach is supported by the DFG (Forschergruppe FOR 302 and SFB 636)     

Latitudinal variation in the shape of the species body size distribution: an analysis using freshwater fishes

Many taxonomic and ecological assemblages of species exhibit a right-skewed body size-frequency distribution when characterized at a regional scale. Although this distribution has been frequently described, factors influencing geographic variation in the distribution are not well understood, nor are mechanisms responsible for distribution shape. In this study, variation in the species body size-frequency distributions of 344 regional communities of North American freshwater fishes is examined in relation to latitude, species richness, and taxonomic composition. Although the distribution of all species of North American fishes is right-skewed, a negative correlation exists between latitude and regional community size distribution skewness, with size distributions becoming left-skewed at high latitudes. This relationship is not an artifact of the confounding relationship between latitude and species richness in North American fishes. The negative correlation between latitude and regional community size distribution skewness is partially due to the geographic distribution of families of fishes and apparently enhanced by a nonrandom geographic distribution of species within families. These results are discussed in the context of previous explanations of factors responsible for the generation of species size-frequency distributions related to the fractal nature of the environment, energetics, and evolutionary patterns of body size in North American fishes.     

Silver nitrate and aminoethoxyvinylglycine affect <Emphasis Type="Italic">Agrobacterium</Emphasis>-mediated apple transformation

In Fuji, the production of ethylene was increased with the addition of AgNO₃ and inhibited with the addition of 10 M aminoethoxyvinylglycine (AVG). The addition of 80 M AgNO₃ to transformed explants of Fuji cultured on selection medium resulted in increased ethylene production (20 l l^–1) at 3 weeks. Under examining the effect of AgNO₃ in Fuji, the 40 M AgNO₃ showed with higher 33.8% and 6.5% in the efficiency of regeneration and transformation. However, ethylene production in Gala explants treated with 10M AgNO₃ (3 l l^–1) decreased after 2 weeks compared with the control (5 l l^–1). Although the regeneration efficiency of Gala with 10 M AgNO₃ was higher (41.1%) than the control (20.1%), there was no significant difference in the transformation efficiency at the same concentration. Shoot regeneration of Fuji and Gala was completely inhibited with 10 M AVG. These results suggest that the addition of AgNO₃ affects the efficiency of Agrobacterium-mediated gene transfer in Fuji.Eun Soo Seong, Ill Min Chung- These two Authors Contributed equally to this work     

The state of the environment of the Loosdrecht lakes

The Loosdrecht lakes are a system of shallow, interconnected, peat lakes in the centre of The Netherlands. The main environmental functions of the Loosdrecht lakes are nature and recreation. From the point of view of the Dutch policy, a Specific Environmental Quality (Bijzondere Milieukwaliteit) should be set for these lakes.The most serious environmental problem of the area is eutrophication. The Loosdrecht lakes have, by increasing external phosphorus loading, changed, from clear lakes with few macrophytes, followed by a period of abundant characean growth, to turbid lakes dominated by cyanobacteria and detrital matter. Eutrophication was counteracted by use of sewerage systems and dephosporization of the supply water. The resultant decrease in external phosphorus loading did not result in a decrease of turbidity by suspended particles.The eutrophication of the lake ecosystems was described as a series of phases. One of those phases, the status around 1940, has been used as an ecological reference system.By means of a graphical presentation technique, the so-called AMOEBE-approach, the state of the environment of the Loosdrecht lakes has been visualized. Thirty-two ecological parameters, including both biotic and abiotic factors, have been selected and quantified. Concrete target values for these parameters have been derived from historical reports and from Lake Western Loenderveen, located close to the Loosdrecht lakes, but less eutrophic.The general conclusion is that the state of the environment of the Loosdrecht lakes is far from what is required with respect to a Specific Environmental Quality, as many of the selected parameters, like water transparency, total phosphorus, mineral nitrogen, cyanobacteria, bream, pike, macrophytes, birds and otter, deviate by over an order of magnitude from their desired levels.     

Mictic patterns of the rotifer Brachionus plicatilis Müller in small ponds

Populations of the rotifer Brachionus plicatilis were monitored in three small ponds in a marsh on the Mediterranean coast. Samples were taken approximately every three weeks from July 1992 to November 1993. Salinity, temperature, conductivity, pH and oxygen concentration were measured in the field. Population density was determined from preserved quantitative samples. Individuals were classified as mictic females, amictic females, non-ovigerous females, and males, differentiating between two morphotypes (S and L). From these counts, a level of mixis was calculated. We also determined the proportion of mictic females in natural populations by culturing females isolated from fresh samples. From these data, mictic patterns over time and correlation between levels of mixis and environmental and population parameters were analyzed. From a previous study S and L morphotypes were known to correspond to genetically different clonal groups. Our data showed that reproduction was predominantly parthenogenetic in these clonal groups, but mictic females were found in most samples, the proportion of mictic females ranging from 0 to 29%. The clonal groups showed different patterns of mixis. L clonal group presented a continuous sexual reproductive pattern. In contrast, S clones showed a rather punctuated mictic pattern. A positive correlation between levels of sexual reproduction and population density was found for S and L groups. However, they differed in their density threshold for mictic reproduction. The adaptive meaning of these patterns and their implications in maintaining genetic diversity within and between populations are discussed.     

Molecular link between cholesterol,cytokines and atherosclerosis

Current investigation on the origin of atherosclerosis has initiated an intense debate over whether atherosclerosis results from hypercholesterolemia or an inappropriate immune response to vascular injury. Although the role of the immune system has been questioned, the overwhelming body of evidence clearly indicates that atherogenesis is initiated by the interplay between cholesterol and cellular secretion of cytokines (especially IL-6) and apolipoprotein E within the arterial wall. Recent studies have revealed that cells possess two cholesterol-sensors: (a) Receptor-C_k which senses the extracellular cholesterol and initiates signalling pathway responsible for the regulation of genes involved in the cell cycle, cell death, cellular cholesterol homeostasis and cytokines including IL-6; (b) LxR which senses intracellular oxysterols and controls genes involved in cell death, cellular cholesterol homeostasis and cytokine IL-8. These cholesterol sensors define the molecular mechanism responsible for cholesterol-depended regulation of cellular synthesis and secretion of cytokines (IL-6, IL-8) within arterial wall. On the basis of this mechanism, presence of cholesterol and its oxy-derivative in the modified LDL will result in transient activation/deactivation of Receptor-C_k-dependent genes which will give rise to repeated cycles of growth coupled with apoptosis leading to a situation where apoptotic-deficient cells in the arterial wall, would be selected resulting in their accumulation and formation of oligoclonal atherosclerotic plaque.     

Imaging gene expression in the brain with peptide nucleic acid (PNA) antisense radiopharmaceuticals and drug targeting technology

Summary Antisense oligomers are potential pharmaceutical and radiopharmaceutical agents that can be used to modulate and image gene expression. Progress with in vivo gene targeting using antisense-based therapeutics has been slower than expected during the last decade, owing to poor trans-cellular delivery of antisense agents. This chapter suggests that if antisense pharmacology is merged with drug targeting technology, then membrane barriers can be circumvented and antisense agents can be delivered to tissues in vivo. Without the application of drug targeting, the likelihood of success for an antisense drug development program is low, particularly for the brain which is protected by the blood-brain barrier (BBB). Among the different classes of antisense agents, peptide nucleic acids (PNA) present advantages for in vivo applications over conventional and modified oligodeoxynucleotides (ODN), including phosphorothioates (PS)-ODN. Some advantages of PNAs include their electrically neutral backbone, low toxicity to neural cells, resistance to nucleases and peptidases, and lack of binding to plasma proteins. PNAs are poorly transported through cellular membranes, however, including the BBB and the brain cell membrane (BCM). Because the mRNA target for the antisense agent lies within the cytosol of the target cell, the BBB and the BCM must be circumvented in vivo, which is possible with the use of chimeric peptide drug targeting technology. Chimeric peptides are formed by conjugation of a non-transportable drug, such as a PNA, to a drug delivery vector. The vector undergoes receptor-mediated transcytosis (RMT) through the BBB and receptor-mediated endocytosis through the BCM in vivo. When labeled with a radioisotope (e.g., ¹²⁵I or ¹¹¹In), the antisense chimeric peptide provides imaging of gene expression in the brain in vivo in a sequence-specific manner. Further development of antisense radiopharmaceutical agents may allow for in vivo imaging of genes in pathological states, and may provide tools for the analysis of novel genes with functional genomics.     

Stages in the development of Parkinson’s disease-related pathology

The synucleinopathy, idiopathic Parkinsons disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1–2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3–4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5–6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.Funding for this project was made available by the German Research Council (Deutsche Forschungsgemeinschaft)     

The wise use of wetlands: identifying development options for Ghana's coastal Ramsar sites

The Government of Ghana has recently declared five coastal wetlands to be Ramsar sites. This requires the wise use of wetlands of international importance for bird habitat, but does not preclude human habitation or ecologically friendly development. The sites are Muni-Pomadze, Densu Delta, Sakumo, Songor and Keta. An attempt was made to identify and assess a range of development options for initiation within the sites that would be compatible with the environmental concerns of Ramsar, while also being technically and economically viable and socially acceptable to the communities in the sites. The appraisal included developing a detailed understanding of the physical, biological, human and institutional resources of the areas, the land uses and prevailing livelihood systems of local people, and the pressures placed on the natural resources of the wetlands. Many of the developments nominated by stakeholders were rejected, but twenty topics passed the initial tests. These were considered in more detail using information collected for the study by national specialists. Most of the options were considered suitable for local level implementation by community groups or local entrepreneurs. Government assistance will be needed to ensure an enabling institutional framework for small-scale business development is provided.     

The giant neurone system in ophiuroids

Summary The radial nerve cords of members of the class Ophiuroidea consist of two parts, the ectoneural and the hyponeural tissues, which are separated by an acellular basal lamina. The hyponeural tissue is composed entirely of motor fibres. The cell bodies of the hyponeural neurones are arranged in ganglia, one to each segment of the arm, and each containing approximately one hundred cell bodies. Synaptic contact between the two tissues occurs across the basal lamina. Ultrastructural evidence shows that the majority of these synapses operate in the ectoneural to hyponeural direction. Three pairs of nerve bundles, each containing approximately thirty five large motor fibres arise from each ganglion and innervate the intervertebral muscles. The large motor fibres divide into a number of pre-terminal axons in the region in which the motor fibre enters the muscle block. The terminal axons run at right-angles across the muscle fibres and neuromuscular junctions are found at the points of contact between the two; each terminal axon makes contact with a large number of muscle fibres. The hyponeural axons also pass through the juxtaligamental tissue before they reach the muscle blocks and there is some evidence of synaptic contact with the juxtaligamental cells. The juxtaligamental tissue is thought to be associated with changes in the structural properties of the collagenous ligaments of the arm during arm autotomy (Wilkie 1979). Degeneration studies confirmed the layout of the hyponeural motor axons.     

Are biodiversity ‘hotspots’ correlated with current ecoclimatic stability? A pilot study using the NOAA-AVHRR remote sensing data

The GAC (Global Area Coverage) by the NOAA-AVHRR satellites represents an excellent data set for studying global and regional patterns of variations in surface conditions driven in part by climatic variation. In this pilot study we examined whether biodiversity hotspots, defined from peak concentrations of neoendemics as well as geographically relict forms, differ in ecoclimatic stability from surrounding areas under present-day climatic conditions. Coefficients of variation of the ratio between brightness surface temperature (Ts) and the Normalized Difference Vegetation Index (NDVI) based upon 10 years' monthly composited scenes of tropical Africa revealed distinctive geographical patterns of interannual variability in surface conditions. Regions with a predominance of old species are characterized by spatial uniformity in the ecoclimatic variability, while regions where rapidly radiating groups dominate are spatially complex in this respect. However, the exact hotspots, with peak concentrations of endemic species, are characterized by a local reduction in ecoclimatic variability, or placement on the boundary to a stable region. This relationship was supported statistically by comparing ecoclimatic profiles across montane forests representing hotspots, and those of other montane forests. It is suggested that, because of interactions between prevailing atmospheric flows, topography and vegetation, the impact of extreme weather is moderated locally. The correlation between current stability and aggregates of neoendemics as well as old relics indicate that local moderation of climatic extremes persist through shifting climatic periods, permitting populations of unique species to survive in these places. The results are used to identify study sites for better ground truthing and for paleoclimatological studies which may be useful for more thorough studies of these relationships.     

Histological changes of the dopaminergic nigrostriatal system in aging

Although the maximum human lifespan has not increased in recent history, average life expectancy has risen dramatically since the beginning of the last century. Lengthening of lifespan has little merit if the quality of life is not preserved. In the elderly, the decline in memory and cognitive abilities is of great concern, as is motor weakening, which increases with age. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. Therefore, the aging of this system has both clinical and vocational aspects. This review includes studies quantitating age-related changes of the nigrostriatal system, with emphasis on the use of stereological methods, and provides tables of stereological studies performed in the nigrostriatal system.We acknowledge the Danish Parkinson Foundation and the Foundation of Stockbroker Henry Hansen and wife for financial support     

Polyphenols as Regulators of Plant-litter-soil Interactions in Northern California's Pygmy Forest: A Positive Feedback?

The convergent evolution of polyphenol-rich plant communities has occurred on highly acidic and infertile soils throughout the world. The pygmy forest in coastal northern California is an example of an ecosystem on an extremely infertile soil that has exceptionally high concentrations of polyphenols. Many negative feedbacks have been identified whereby plants degrade fertile soils through production of polyphenol-rich litter, sequestering soil nutrients into unavailable form and creating unfavorable conditions for seed germination, root growth, and nutrient uptake. But in the context of plant-litter-soil interactions in ecosystems adapted to soils that are inherently acidic and infertile (such as the pygmy forest), there are also many positive feedbacks that result from polyphenol production. By inhibiting decomposition, polyphenols regulate the formation of a mor-humus litter layer, conserving nutrients and creating a more favorable medium for root growth. Polyphenols shift the dominant pathway of nitrogen cycling from mineral to organic forms to minimize potential N losses from the ecosystem and maximize litter-N recovery by mycorrhizal symbionts. Polyphenol complexation of Al, Mn and Fe reduce potential Al toxicity and P fixation in soil. Polyphenols regulate organic matter dynamics, leading to the accumulation of organic matter with cation exchange capacity to minimize leaching of nutrient cations. Humic substances derived from polyphenolic precursors coat rhizosphere soil surfaces, improving physical and chemical conditions for root growth and nutrient cycling. Although their long-accepted adaptive value for antiherbivore defense is now in doubt, polyphenol alteration of soil conditions and regulation of nutrient cycling illustrate how fitness can be influenced by the extended phenotype in plant-litter-soil interactions.     

The role of ‘Norin 10’ dwarfing genes in photosynthetic and respiratory activity of wheat leaves

Summary A comparative analysis of eight cultivars of spring wheat (Triticum aestivum) classified by height as tall (T), semi-dwarf (D₁), dwarf (D₂) and very dwarf (D₃) was conducted to study their efficiency of oxygen exchange during photosynthesis and dark respiration. Two cultivars were included in each height group.Cultivars carrying Norin 10 dwarfing genes (D₁, D₂ and D₃) were found to have a significantly higher photosynthetic rate per unit leaf area than talls (T) that lack these genes. Among the Norin gene carriers, dwarf group (D₂) was most efficient, followed by very dwarf (D₃) and semi-dwarf (D₁).Photosynthetic rate and respiratory rate were found to have a positive relationship.     

Evidence suggesting energy-dependent formaldehyde transport in an RuMP-type methylotroph (T15)

Formaldehyde accumulation ratios ([¹⁴CH₂O]_i/[¹⁴CH₂O]_o) as high as 12-fold were measured in anaerobic, CH₃OH-energized, whole cell suspensions of the ribulose monophosphate (RuMP)-type methylotrophic strain T15. Uptake kinetics were extremely rapid, enabling the attainment of equilibrium in only 10–30 s. Transport appears to be energy-dependent and associated with the protonmotive force (pmf). Anaerobic incubation with 5 M carbonyl p-(trifluoromethoxy)-phenylhydrazone (FCCP) led to 70%–90% reduction of the accumulation ratio. Though not as pronounced, diminished uptake was also observed in the presence of 140 M nigericin, 161 M valinomycin and 90 mM KSCN, commensurate with their effects on pmf. Accumulation of CH₂O as a function of external pH followed a trend more similar to that of pmf than either pH or . Preventing energization by incubation with 100 M N,N-dicyclohexylcarbodiimide (DCCD) led to nearly 80% inhibition of CH₂O transport. Over short time periods it was possible to chase accumulated ¹⁴CH₂O from previously loaded cells by collapsing pmf; however, this technique also indicated that significant ¹⁴CH₂O incorporation began to occur within 3 min.Abbreviations FCCP Carbonyl cyanide p-(trifluoromethyoxy)-phenylhydrazone - DCCD N,N-dicyclohexylcarbodiimide - RuMP ribulose monophosphate - TPP⁺ tetra[U-¹⁴C]phenylphosphonium - pmf protonmotive force