Catalytic biotransformation of physiologically active 1-methyl-4- aryl-1,2,3,6-tetrahydropyridines under the action of monoaminooxidase

Kinetics of monoamine oxidase (MAO) catalyzed dehydrogenation of neurotropic analogues of biogenic monoamines in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine series were studied. It is shown that methyl substitution in the phenyl ring increases significantly the enzyme-substrate affinity, but the substituent's effect on the catalytic stage largely depends upon its position in the ring. o- and m-Methyl derivatives were preferably oxidized by B type of MAO, whereas p-total derivative was oxidized by B type as well as by A type of the enzyme. In the course of the oxidation reactions MAO is irreversibly inhibited by the dihydropyridinium product of the reaction, particularly in case of methyl derivatives. The significant and structure-dependent inhibition of the enzyme might be responsible for the differences in neurotropic properties of the above substrate homologues.     

Fused in Sarcoma (FUS) Protein Lacking Nuclear Localization Signal (NLS) and Major RNA Binding Motifs Triggers Proteinopathy and Severe Motor Phenotype in Transgenic Mice

Dysfunction of two structurally and functionally related proteins, FUS and TAR DNA-binding protein of 43 kDa (TDP-43), implicated in crucial steps of cellular RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. The proteins are intrinsically aggregate-prone and form non-amyloid inclusions in the affected nervous tissues, but the role of these proteinaceous aggregates in disease onset and progression is still uncertain. To address this question, we designed a variant of FUS, FUS 1–359, which is predominantly cytoplasmic, highly aggregate-prone, and lacks a region responsible for RNA recognition and binding. Expression of FUS 1–359 in neurons of transgenic mice, at a level lower than that of endogenous FUS, triggers FUSopathy associated with severe damage of motor neurons and their axons, neuroinflammatory reaction, and eventual loss of selective motor neuron populations. These pathological changes cause abrupt development of a severe motor phenotype at the age of 2.5–4.5 months and death of affected animals within several days of onset. The pattern of pathology in transgenic FUS 1–359 mice recapitulates several key features of human ALS with the dynamics of the disease progression compressed in line with shorter mouse lifespan. Our data indicate that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in transgenic mice.     

Calcium-dependent chloride current in rat cerebellar Purkinje cell membranes

The presence of calcium-dependent potential-activated chloride currents in the membranes of freshly isolated rat cerebellar Purkinje cells (12–15 days) was shown by the whole-cell patch clamp technique. Chloride currents appeared in a sodium-free external solution and reversibly disappeared in the absence of external chloride and calcium ions.     

Molecular changes in inbred mice with individual vulnerability vs resilience to stress-induced depressive-like state

The C57BL/6 mice were subjected to a chronic combined stress which resulted in the induction of a depressive-like state. The occurrence of a depressive-like state was defined by a decrease in sensitivity to the reward determined by the diminished preference of sweetened solutions over regular drinking water. Such decrease is generally considered as a sign of an unhedonic-like state: one of the key features of clinical depression. Applied here, the paradigm in mice allows unhedonia induction in a subpopulation of stressed animals (54% in the current study); remaining mice are regarded as resilient to stress-induced hedonic deficit. The resilient subgroup is taken, therefore, as a "functional control" for those effects of stress that are not accompanied by development of the stress-induced depressive-like state in mice. The analysis of the mRNA extracted from the hippocampi of stress-subjected and home-cage control mice enabled the assessment of gene expression level of over 13 000 genes. This study showed that unhedonic mice are characterized by an up-regulation of 278 and down-regulation of 174 genes related mostly to the CNS development and functions, inter-cellular interactions and signalling, neurological disorders, apoptosis and behavioural regulation. Resilient animals demonstrated up-regulation of 924 and down-regulation of only 29 genes that control formation of cell assemblies, molecular transport, CNS functioning, neurological disorders and various biochemical reactions. Thus, gene expression profiles in the hippocampus of susceptible vs resilient to stress-induced unhedonia inbred subgroups of animals are strictly distinct in both quantity and quality.     

Intra-annual genetic variation in the downstream larval drift of sutchi catfish (Pangasianodon hypophthalmus) in the Mekong river

Larvae of the sutchi catfish Pangasianodon hypophthalmus were collected during peak downstream drift in the Lower Mekong river on four occasions over an 8-week period during the 2003 spawning season, and genotyped using seven microsatellite loci. We provide evidence for several heterogeneous groups within and among the temporally discrete larval peak samples. Strong evidence for a significant deficit of heterozygotes was observed for each larval sample and the pooled sample, possibly due to population admixture. Although individual-based assignment tests suggested that each larval peak sample was admixed, significant but low genetic differentiation was observed among larval samples ( F _ST = 0.0052, P  < 0.01). The lack of significant relatedness confirms the multifamily composition of each larval group, excluding family bias to explain the observed genetic heterogeneity. Both the entire larval peak and each temporally separated larval peak originated from spawning groups with heterogeneous allelic composition involving several distinct spawning events. We propose three explanations to account for our findings: (1) the ecological match/mismatch hypothesis; (2) the genetic 'sweepstakes' selection hypothesis; and (3) life-history-specific characteristics of the spawning populations. Finally, an intra-annual shift in the contribution of the spawning populations to the larval drift was detected on successive occasions.  © 2006 The Linnean Society of London, Biological Journal of the Linnean Society , 2006, 89 , 719–728.     

Insecticidal activities of Ginkgo biloba seed coat extracts against Spodoptera exigua (Lepidoptera: Noctuidae)

The present study relates to a methanol extract of the seed coat of Ginkgo biloba, and tested particularly on the third instar larvae of Spodoptera exigua. The extract was found to have an inhibitory effect on the growth of the larvae besides bringing a change in the nutrient reserves in the body of the insect. Topical application of five different doses of the methanol extract resulted in a mortal effect to third instar larvae of S. exigua that is very much dependent on the dose as well as duration of exposure. Lower doses revealed lower mortality after 24 h of application. At doses of 1.00, 2.00, 4.00, 8.00 and 16.00 ng/larva, mortalities were 9.25, 26.07, 50.32, 56.28 and 92.44%, respectively. The dose for 50% mortality (LD₅₀) of methanol extracts by applied by a topical method with 1 µL of acetone solution was 1.92 ng/larva. Nutrient reserves like protein, glycogen and lipid are known to regulate pupation and adult emergence. These reserves have been found to be lower in treated larvae, indicating the insecticidal role of methanol extracts from G. biloba against third instar larvae of S. exigua.     

Riccia fruticulosa O.F.Müll., 1782 and blue Metzgeria (Marchantiophyta) in Europe

Riccia fruticulosa O.F.Müll., 1782 from Norway is a valid name, referring to Riccardia palmata (Hedw.) Carruth. In 1785 Dickson misidentified British plants of a blue Metzgeria as R. fruticulosa . The European blue species of Metzgeria is conspecific with M. violacea (Ach.) Dumort., which replaces M. fruticulosa auct. The true origin of the type of Jungermannia violacea Ach., 1805 is probably Tierra del Fuego (rather than Dusky Bay, New Zealand), where the species is widespread. Reports from Australasia, Asia and Africa are all erroneous. The blue colour of Jungermanniales is found only in living plants and is derived from the oil-bodies. In contrast, that of Metzgeria appears only after death; its biological function is unknown.  © 2003 The Linnean Society of London, Botanical Journal of the Linnean Society, 2003, 142 , 229−235.     

Evaluation of the capability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and pyridine derivatives to evoke parkinsonism

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produce an irreversible parkinsonian-like syndrome in humans, monkeys and mice C57BL/6. Experimental parkinsonism produced by MPTP on mice C57BL/6 were studied with the aim of working up the method for testing MPTP-like substances. It has been shown that intraperitoneal administration the maximal tolerated doses of MPTP cause significant decrease (by 40-60%) of dopamine content on the mice brain. Number of injections did not influence the results. The similar administration of 4-phenyl-pyridyl and 4,4'-dipyridyl derivates, including known herbicides paraquat and cyperquat, produce neither decrease of dopamine content in the brain, nor the development of parkinsonian-like behavioral syndrome.     

Variations in the life-history parameters of Hemipyrellia ligurriens (Diptera: Calliphoridae) in response to larval competition for food

Abstract. 1. Larval rearing densities of Hemipyrellia ligurriens (Wiedemann) (Diptera: Calliphoridae) in standardized carrion were manipulated in order to investigate changes in life-history parameters in response to larval competition for food.
2. Competition was of the typical scramble type. Survivorship remained high at densities up to 32 larvae g liver^-1 but decreased rapidly as larval density increased further.
3. Emergent adults were undersized with reduced fecundity and longevity. Variations in adult body size apparently reduced the effects of competition on larval mortality.
4. Females of dry weight corresponding to only 10.4% of the potential maximum emerged at the highest rearing densities of 128 larvae g liver-1. However, these females had a nearly four-fold increase in reproductive investment (per unit weight) when compared to the largest individuals.
5. The duration of larval development declined when competition was intense (i.e. at high larval densities).
6. The short adult life of H.ligurriens, combined with the unpredictability of larval habitat availability, may reduce the value of long-range dispersal so that females 'do better' by maintaining reproductive investment despite a concomitant decline in dispersal ability.