Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia

Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia.     

The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2

The human C-type lectin-like molecule CLEC-2 is expressed on the surface of platelets and signaling through CLEC-2 causes platelet activation and aggregation. CLEC-2 is a receptor for the platelet-aggregating snake venom protein rhodocytin. It is also a newly identified co-receptor for human immunodeficiency virus type 1 (HIV-1). An endogenous ligand has not yet been identified. We have solved the crystal structure of the extracellular domain of CLEC-2 to 1.6-A resolution, and identified the key structural features involved in ligand binding. A semi-helical loop region and flanking residues dominate the surface that is available for ligand binding. The precise distribution of hydrophobic and electrostatic features in this loop will determine the nature of any endogenous ligand with which it can interact. Major ligand-induced conformational change in CLEC-2 is unlikely as its overall fold is compact and robust. However, ligand binding could induce a tilt of a 3-10 helical portion of the long loop region. Mutational analysis and surface plasmon resonance binding studies support these observations. This study provides a framework for understanding the effects of rhodocytin venom binding on CLEC-2 and for understanding the nature of likely endogenous ligands and will provide a basis for rational design of drugs to block ligand binding.     

Uraninschwellen des Protoplasmas der BraunalgeStypocaulon scoparium

Ohne Zusammenfassung     

Zum Bewegungssehen des Mehlkäfers Tenebrio molitor

Summary The locomotory turns of the beetle Tenebrio molitor were recorded from free walking animals which were held in stationary position and orientation by means of a tread compensator. Striped patterns revolved around an animal elicit optomotor responses which undergo an inversion at smaller stripe widths. The position of the inversion point characterizes the resolving power of the motion detectors, and corresponds to a 6.5° average angle between the optical axes of interacting elements in the motion detecting device. This indirectly determined value is consistent with the anatomically measured 7° average angle between the axes of neighbouring ommatidia in the Tenebrio compound eye.     

Antennale Rezeptoren für Queen Substance und Sterzelduft bei der Honigbiene

Zusammenfassung Auf den Antennen aller drei Kasten von Apis mellifica konnten elektrophysiologisch 2 Typen von Riechzellen identifiziert werden, die auf Pheromone der Biene antworten. Der eine Typ ist auf Queen substance (9-Oxo-trans-2-decensäure), der andere auf den Sterzelduft der Arbeiterin spezialisiert. Beide Zelltypen werden bei Ableitungen von Porenplatten gefunden.

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Antennal receptors for queen substance and scent gland odour in honeybees

Summary Electrophysiologically, we could identify two types of olfactory receptor cells, which respond to pheromones of the honeybee. These cells are associated with the poreplates on the antennae of all three castes of Apis mellifica. One of the cell types is specialized for the queen substance (9-oxo-trans-2-decenoic acid) while the other responds to the scent of the Nasanov gland.

     

Metallothionein induction by nonsteroidal antiinflammatory drugs

In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA).     

Different oligosaccharides accumulate in the brain and urine of a cat with α-mannosidosis: structure determination of five brain-derived and seventeen urinary oligosaccharides

Five brain-derived and 17 urinary oligomannose-type oligosaccharides were isolated by ion-exchange chromatography on Mono Q or Dowex, followed by HPLC on Lichrosorb-NH₂ from a Persian cat suffering from -mannosidosis. The structures ofthe carbohydrate chains were determined by 500- or 600-MHz¹H-NMR spectroscopy. Different oligosaccharide patterns were found in brain and urine. 99% of the urinary oligosaccharides possess an (1-6)-linked mannose residue attached to -mannose, whereas only 5% of the brain-derived oligosaccharides contain such a residue. Furthermore, of the urinary carbohydrate chains 71% end with Man1-4GlcNAc1-4GlcNAc and 29% end with Man1-4GlcNAc, whereas the corresponding amounts are 23% and 77%, respectively, for the brain-derived oligosaccharides.Abbreviations MLEV-17 composite pulse devised by M. Levitt - HOHAHA homonuclear Hartman-Hahn spectroscopy - TPPI time-proportional phase incrementation - 2D two dimensional - GlcNAc N-acetylglucosamine - Man mannose - Fuc fucose     

Summer zooplankton dynamics in the limnetic and littoral zones of a humic acid lake

The limnetic and littoral zooplankton were studied during summer 1989 in Triangle Lake, a humic acid (pH 4.9) bog lake in Ohio, USA. The limnetic zooplankton showed low species richness and biomass, and dominance by the rotifers Kellicottia bostoniensis and Polyarthra vulgaris. In the littoral, species richness and biomass were markedly higher, and the crustaceans Alona guttata, Ceriodaphnia quadrangula, Chydorus sphaericus, Simocephalus serrulatus and Tropocyclops prasinus, and the rotifer Ascomorpha ecaudis were the dominants. The extreme rotifer dominance and lack of cladocerans in the limnetic zone were likely the result of Chaoborus predation. A pronounced mid-summer decline in cladoceran biomass in the littoral was likely due to predation by T. prasinus and Utricularia (bladderwort).     

Sleep Promotes the Extraction of Grammatical Rules

Grammar acquisition is a high level cognitive function that requires the extraction of complex rules. While it has been proposed that offline time might benefit this type of rule extraction, this remains to be tested. Here, we addressed this question using an artificial grammar learning paradigm. During a short-term memory cover task, eighty-one human participants were exposed to letter sequences generated according to an unknown artificial grammar. Following a time delay of 15 min, 12 h (wake or sleep) or 24 h, participants classified novel test sequences as Grammatical or Non-Grammatical. Previous behavioral and functional neuroimaging work has shown that classification can be guided by two distinct underlying processes: (1) the holistic abstraction of the underlying grammar rules and (2) the detection of sequence chunks that appear at varying frequencies during exposure. Here, we show that classification performance improved after sleep. Moreover, this improvement was due to an enhancement of rule abstraction, while the effect of chunk frequency was unaltered by sleep. These findings suggest that sleep plays a critical role in extracting complex structure from separate but related items during integrative memory processing. Our findings stress the importance of alternating periods of learning with sleep in settings in which complex information must be acquired.