Das Hörvermögen der Nachtschmetterlinge

Zusammenfassung An zahlreichen Exemplaren von Noctuiden, Geometriden, Notodontiden und Arctiiden wurden Reaktionen auf Schallwellen des Frequenzbereiches 15–175 kHz beobachtet, die sämtlich Flucht- oder Totstellreaktionen waren und nach Häufigkeit und Intensität ihre niedrigste Schwelle im Bereich von 40–80 kHz haben.Die Reaktionen sind nicht artspezifisch.Durch Exstirpationsversuche konnte gezeigt werden, daß die Schallreize peripher in den Tympanalorganen aufgenommen, zentral kritisch verarbeitet werden und dann zu den beschriebenen Reaktionen führen. Diese sind also nicht reflektorisch entstanden, sondern müssen als Ausdruck echten Hörens aufgefaßt werden.Dieselben Reaktionen werden beobachtet, wenn Nachtfalter mit Fledermäusen konfrontiert werden, deren Orientierungslaute im selben Frequenzbereich liegen wie die niedrigsten Schwellen der Nachtfalter.Aus allem wird der Schluß gezogen, daß Nachtfalter Fledermäuse hören können, sich ihrem Zugriff durch Flucht oder Totstellen entziehen und dadurch einen relativen Schutz vor ihren Feinden besitzen.     

Microtubule affinity-regulating kinase 2 (MARK2) turns on phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) at Thr-313, a mutation site in Parkinson disease: effects on mitochondrial transport

The kinase MARK2/Par-1 plays key roles in several cell processes, including neurodegeneration such as Alzheimer disease by phosphorylating tau and detaching it from microtubules. In search of interaction partners of MARK2, we identified phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), which is important for the survival of neurons and whose mutations are linked to familial Parkinson disease (PD). MARK2 phosphorylated and activated the cleaved form of PINK1 (ΔN-PINK1; amino acids 156-581). Thr-313 was the primary phosphorylation site, a residue mutated to a non-phosphorylatable form (T313M) in a frequent variant of PD. Mutation of Thr-313 to Met or Glu in PINK1 showed toxic effects with abnormal mitochondrial distribution in neurons. MARK2 and PINK1 were found to colocalize with mitochondria and regulate their transport. ΔN-PINK1 promoted anterograde transport and increased the fraction of stationary mitochondria, whereas full-length PINK1 promoted retrograde transport. In both cases, MARK2 enhanced the effects. The results identify MARK2 as an upstream regulator of PINK1 and ΔN-PINK1 and provide insights into the regulation of mitochondrial trafficking in neurons and neurodegeneration in PD.     

Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2

MARK/Par-1, a kinase family with diverse functions particularly in inducing cell polarity, can phosphorylate microtubule-associated proteins in their repeat domain and cause their detachment from microtubules, and thereby microtubule destabilization. Because of its role in abnormal phosphorylation of the Tau protein in Alzheimer disease, we searched for regulatory kinases. MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. Because GSK3beta can also phosphorylate Tau at sites outside the repeat domain, the activation of GSK3beta, and concomitant inactivation of MARK can shift the pattern of pathological phosphorylation of Tau protein in Alzheimer disease.     

Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor

Fumarylacetoacetate hydrolase (FAH) catalyzes the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step of Phe and Tyr degradation. This unusual reaction is an essential human metabolic function, with loss of FAH activity causing the fatal metabolic disease hereditary tyrosinemia type I (HT1). An enzymatic mechanism involving a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole was previously proposed based on recently determined FAH crystal structures. Here we report the development and characterization of an FAH inhibitor, 4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid (HMPOBA), that competes with the physiological substrate with a K(i) of 85 microM. The crystal structure of FAH complexed with HMPOBA refined at 1.3-A resolution reveals the molecular basis for the competitive inhibition, supports the proposed formation of a tetrahedral alkoxy transition state intermediate during the FAH catalyzed reaction, and reveals a Mg(2+) bound in the enzyme's active site. The analysis of FAH structures corresponding to different catalytic states reveals significant active site side-chain motions that may also be related to catalytic function. Thus, these results advance the understanding of an essential catabolic reaction associated with a fatal metabolic disease and provide insight into the structure-based development of FAH inhibitors.     

Der Energiestoffwechsel in verschiedenen Organen der Ratte nach Ganzkörperbestrahlung mit verschiedenen Strahlendosen

Ohne Zusammenfassung     

Transmedulla Neurons in the Sky Compass Network of the Honeybee (Apis mellifera) Are a Possible Site of Circadian Input

Honeybees are known for their ability to use the sun’s azimuth and the sky’s polarization pattern for spatial orientation. Sky compass orientation in bees has been extensively studied at the behavioral level but our knowledge about the underlying neuronal systems and mechanisms is very limited. Electrophysiological studies in other insect species suggest that neurons of the sky compass system integrate information about the polarization pattern of the sky, its chromatic gradient, and the azimuth of the sun. In order to obtain a stable directional signal throughout the day, circadian changes between the sky polarization pattern and the solar azimuth must be compensated. Likewise, the system must be modulated in a context specific way to compensate for changes in intensity, polarization and chromatic properties of light caused by clouds, vegetation and landscape. The goal of this study was to identify neurons of the sky compass pathway in the honeybee brain and to find potential sites of circadian and neuromodulatory input into this pathway. To this end we first traced the sky compass pathway from the polarization-sensitive dorsal rim area of the compound eye via the medulla and the anterior optic tubercle to the lateral complex using dye injections. Neurons forming this pathway strongly resembled neurons of the sky compass pathway in other insect species. Next we combined tracer injections with immunocytochemistry against the circadian neuropeptide pigment dispersing factor and the neuromodulators serotonin, and γ-aminobutyric acid. We identified neurons, connecting the dorsal rim area of the medulla to the anterior optic tubercle, as a possible site of neuromodulation and interaction with the circadian system. These neurons have conspicuous spines in close proximity to pigment dispersing factor-, serotonin-, and GABA-immunoreactive neurons. Our data therefore show for the first time a potential interaction site between the sky compass pathway and the circadian clock.     

Trypanosoma cruzi: isolation and characterization of membrane and flagellar fractions.

A cell fractionation procedure for obtaining membrane and flagellar fractions was developed using Trypanosoma cruzi epimastigote forms. The cells, swollen in an hypotonic medium, were disrupted in the presence of a nonionic detergent, and fractions were isolated by differential centrifugation. The flagellar fraction, pelleted in 10 min at 10,000g, was further purified on a sucrose gradient. The membrane fraction was obtained by centrifugation of the supernatant at 27,000g for 30 min. Electron microscopy of the isolated fractions demonstrated a high degree of purity of each fraction. The membrane fraction showed homogeneous vesicles with low ribosome content. In frozen-etched preparations, the distribution of intramembranous particles on the vesicles was similar to that of the plasma membrane of intact cells. Enzymatic assays indicated that the membrane and flagellar fractions had low contamination with mitochondria and lysosomes. 5′-Nucleotidase activity was not detected in the membrane fraction; Mg²⁺-dependent ATPase activity was slightly enhanced, although, the enzyme was not sensitive to Na⁺, K⁺, and Ca²⁺ ions. The membrane fraction showed about five times the adenylyl cyclase activity of the whole homogenate. Gel immunodiffusion revealed the whole antigen of T. cruzi extracted by formamide to be identical to the membrane fraction when both were tested against rabbit anti- T. cruzi (epimastigote) immune serum.     

Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance

Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo.     

Predation by and activity patterns of 'parasitic' beetles of the genus Amblyopinus (Coleoptera: Staphylinidae)

This study explores the relationship between staphylinid beetles of the genus Amblyopinus and their small mammal hosts. Previous studies had concluded that these beetles were parasitic and fed directly on blood, skin exudates, or other epidermal derivatives of their hosts. We examined the mode of attachment, behaviour, and feeding activities of 254 Amblyopinus (A. tiptoni and A. emarginatus ) on 69 hosts which were captured in Sherman live traps. In addition, similar information and diurnal activity patterns were monitored for 11 beetles kept on two hosts ( Peromyscus nudipes ) over a period of 14 days. Beetles were found to be attached to the host only by grasping clumps of fur in their mandibles. No sign of damage to the skin of the host could be found. Feeding by the beetles on parasitic arthropods was observed and concluded to be the primary feeding habit. Beetles showed a strong circadian activity pattern, in which they are attached to the host during night-time hours and actively hunt in the nest during daylight hours. Attachment to the host is hypothesized to be primarily a vehicle for tracking prey of the beetles within the variety of nests used by any individual host. We conclude that these beetles are not parasitic but, instead, highly specialized predators on ectoparasitic arthropods, with specialized behavioural and morphological adaptations for their unique life style.