Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice

Serotonin systems have been implicated in the regulation of hippocampal function. Serotonin 5-HT2C receptors are widely expressed throughout the hippocampal formation, and these receptors have been proposed to modulate synaptic plasticity in the visual cortex. To assess the contribution of 5-HT2C receptors to the serotonergic regulation of hippocampal function, mice with a targeted 5-HT2C-receptor gene mutation were examined. An examination of long-term potentiation at each of four principal regions of the hippocampal formation revealed a selective impairment restricted to medial perforant path-dentate gyrus synapses of mutant mice. This deficit was accompanied by abnormal performance in behavioral assays associated with dentate gyrus function. 5-HT2C receptor mutants exhibited abnormal performance in the Morris water maze assay of spatial learning and reduced aversion to a novel environment. These deficits were selective and were not associated with a generalized learning deficit or with an impairment in the discrimination of spatial context. These results indicate that a genetic perturbation of serotonin receptor function can modulate dentate gyrus plasticity and that plasticity in this structure may contribute to neural mechanisms underlying hippocampus-dependent behaviors.     

Ein neues Maschinensystem für die Fixmaßbearbeitung in Großbetrieben

Ohne Zusammenfassung     

Congenital enterocyte heparan sulphate deficiency with massive albumin loss, secretory diarrhoea, and malnutrition

BACKGROUND: The molecular basis of protein-losing enteropathy is unknown. However it has been shown that sulphated glycosaminoglycans may be important in regulating vascular and renal albumin loss. METHODS: We describe three baby boys who presented within the first weeks of life with massive enteric protein loss, secretory diarrhoea, and intolerance of enteral feeds. All required total parenteral nutrition and repeated albumin infusions. No cause could be found in any case despite extensive investigations, including small intestinal biopsy sampling, which were repeatedly normal. FINDINGS: By specific histochemistry, we detected gross abnormality in the distribution of small intestinal glycosaminoglycans in all three infants, with complete absence of enterocyte heparan sulphate. The distribution of vascular and lamina propria glycosaminoglycans was, however, normal. INTERPRETATION: The presentation of these infants suggests that enterocyte heparan sulphate is important in normal small intestinal function.     

The LBA-problem and the deterministic tape complexity of two-way one-counter languages over a one-letter alphabet

Summary It is shown, that NTAPE(n) is equal to TAPE(n) if and only if every language L⊂⊣{1}^*⊢ which is acceptable by a nondeterministic two-way one-counter automaton whose counter length is bounded by the length of its input is contained in TAPE(log n).     

Comparison of biota-sediment accumulation factors across ecosystems

Sets of biota-sediment accumulation factors (BSAFs) for fish were compared across ecosystems for nonionic organic chemicals. The sets of BSAFs, when plotted against each other, in log-log space, formed linear relationships and demonstrated that the relative scaling or ranking of the individual BSAFs within a set are consistent, if not the same, across ecosystems. This behavior holds for chemicals that either are, or are not, metabolized by fish. These results demonstrate that sets of BSAF values can differ but with parallel shifts in magnitude between ecosystems (for example, all of the BSAFs in the set are uniformly larger in one ecosystem, while in another they all are uniformly smaller) in response to underlying differences in ecosystem conditions and parameters such as trophic level, diet of the organisms, and distribution of the chemical between the sediment and water column.     

Occurrence of a nitro metabolite of a defined nonylphenol isomer in soil/sewage sludge mixtures

Uniformly [14C]-ring-labeled 4-(3,5-dimethyl-3-heptyl)phenol (353-nonylphenol) is a highly relevant isomer of the technical nonylphenol mixture. We studied the sorption, desorption, and degradation of the synthesized isomer in an agricultural sandy loam at various soil/sewage sludge ratios. Sorption of 353-nonylphenol was high and differed with the amount of suspended soil in water. log Koc values, which are used to assess the risk of nonylphenol, ranged from 3.80 to 5.75. Desorption was slow and low and resulted in constant concentrations of about 15 ng/L353-nonylphenol in water after several desorption steps. In degradation studies up to 6% of the applied 353-nonylphenol in soil was volatilized; we consider this an important source of nonylphenol in the environment. With increasing amounts of sewage sludge in the soil/sewage sludge mixtures, 353-nonylphenol was stabilized, probably because of the lack of oxygen in sludge aggregates even under oxic conditions in flow-through systems. Unexpectedly, a less-polar metabolite was detected in amounts up to 40% of the applied nonylphenol after 135 days of incubation. This novel metabolite was identified as 4-(3,5-dimethyl-3-heptyl)-2-nitrophenol. This product formation might indicate the existence of novel metabolic pathways of nonylphenol in the environment.     

Einfluß der chemischen Zusammensetzung auf die Relaxationsbehinderung schweißsimulierter warmfester Feinkornbaustähle beim Spannungsarmglühen

Einfluß der Spurenelemente, Bedeutung der Stickstoff-Abbindungsverhältnisse, Aluminiumnitrid, Bornitrid, Absenkung des Kohlenstoffgehaltes, Auswirkung erhöhter Gehalte an Mischkristallbildnern, Warmzugversuche, Zugversuche unter konstanter Kraft.     

Synthesis,Inhibition Potency,Binding Mode,and Antiprotozoal Activities of Fluorescent Inhibitors of Trypanothione Reductase Based on Mepacrine‐Conjugated Diaryl Sulfide Scaffolds

Trypanothione reductase (TR) is a flavoenzyme unique to trypanosomatid parasites and a target for lead discovery programs. Various inhibitor scaffolds have emerged in the past, exhibiting moderate affinity for the parasite enzyme. Herein we show that the combination of two structural motifs of known TR inhibitors — diaryl sulfides and mepacrine — enables the simultaneous addressing of two hydrophobic patches in the active site. The binding efficacy of these conjugates is enhanced over that of the respective parent inhibitors. They show K_ic values for the parasite enzyme down to 0.9±0.1 μm and exhibit high selectivity for TR over human glutathione reductase (GR). Despite their considerable molecular mass and in some cases permanent positive charges, in vitro studies revealed IC₅₀ values in the low micromolar to sub‐micromolar range against Trypanosoma brucei rhodesiense and Trypanosoma cruzi, as well as the malaria parasite Plasmodium falciparum, which lack trypanothione metabolism. The inhibitors exhibit strong fluorescence due to their aminoacridine moiety. This feature allows visualization of the drugs in the parasite where high accumulation was observed by fluorescence microscopy even after short exposure times.