All optical quantum control of a spin-quantum state and ultrafast transduction into an electric current.

The ability to control and exploit quantum coherence and entanglement drives research across many fields ranging from ultra-cold quantum gases to spin systems in condensed matter. Transcending different physical systems, optical approaches have proven themselves to be particularly powerful, since they profit from the established toolbox of quantum optical techniques, are state-selective, contact-less and can be extremely fast. Here, we demonstrate how a precisely timed sequence of monochromatic ultrafast (~ 2-5 ps) optical pulses, with a well defined polarisation can be used to prepare arbitrary superpositions of exciton spin states in a semiconductor quantum dot, achieve ultrafast control of the spin-wavefunction without an applied magnetic field and make high fidelity read-out the quantum state in an arbitrary basis simply by detecting a strong (~ 2-10 pA) electric current flowing in an external circuit. The results obtained show that the combined quantum state preparation, control and read-out can be performed with a near-unity (≥97%) fidelity.

Brain-derived neurotrophic factor prevents the loss of nigral neurons induced by excitotoxic striatal-pallidal lesions.

GABAergic neurons in the rat substantia nigra die after inhibitory inputs to the nigra have been killed, and glutamatergic inputs disinhibited, by striatal-pallidal injections of ibotenic acid. This delayed transneuronal injury model imitates the neuron loss observed in Huntington's disease, and may also imitate neuron loss distant from the primary injury in stroke and Parkinson's disease. Because the neurotrophins brain-derived neurotrophic factor and neurotrophin-3 can prevent excitotoxic killing of cultured GABA neurons, we tested whether either factor could protect nigral neurons from transneuronal degeneration. A continuous, three week supranigral infusion of brain-derived neurotrophic factor completely prevented the loss of nigral neurons caused by the ibotenic acid-induced destruction of the caudate-putamen and globus pallidus, and brain-derived neurotrophic factor increased nigral neuron size by 25%. These effects were specific to the TrkB tyrosine kinase receptor that mediates brain-derived neurotrophic factor actions, since supranigral infusions of saline or the TrkC preferring neurotrophin-3, did not prevent nigral neuron loss or induce a hypertrophic response. Neither trophic factor influenced the ibotenic acid destruction of striatal or pallidal neurons. These results demonstrate that exogenously supplied brain-derived neurotrophic factor can prevent delayed, transneuronal loss, and implicate decreased excitatory amino acid transmission or diminished nigral neuron susceptibility to glutamate inputs in the protective effect of brain-derived neurotrophic factor.

Heterocycles as physiological ligands for the benzodiazepine receptor and for other binding sites.

Recently pharmacologically active benzodiazepines, including diazepam, have been identified in common foodstuffs, e.g. wheat and potato. The chronical intake by way of plant food may explain the existence of benzodiazepines in the brain and in other tissues of various mammalians and man. Hitherto these alkaloid-like compounds were considered to be merely products of industrial synthesis. All the benzodiazepines used in therapy show a similar chemical structure. However, depending on particular substituents, agonistic benzodiazepines can be subdivided into groups of different pharmacological potency. Besides benzodiazepines, in the past years other alkaloid drugs, e.g. derivatives of morphine, norharmane and tetrahydronorharmane, have been isolated from animals. Some of these substances have been discussed as physiological ligands of specific neuronal binding sites. Indications have been provided that at least part of these compounds or their precursors may be of plant origin too. The presence of these compounds in plants used for food may suggest complex interactions between plant and animal, exceeding the nutritional aspect.

Increase of natural benzodiazepines in wheat and potato during germination.

Aqueous acid extracts of wheat grains and potato exhibit after HPLC separation a series of compounds that are able to inhibit the binding of benzodiazepines to benzodiazepine receptors of rat brain membranes. In wheat one of the inhibiting compounds was shown to be identical to diazepam by means of HPLC characterization and gas chromatography combined with mass spectrometry. In potato one of the most prominent components in terms of binding inhibiting activity was identified as lormetazepam. In wheat and potato germination increases total inhibiting activity of the whole plant extracts as well as the content of the benzodiazepines approximately by factor five. Because uptake of benzodiazepines from the surrounding was excluded these findings indicate the biosynthesis of the benzodiazepines diazepam and lormetazepam by the plants investigated.

Occurrence of pharmacologically active benzodiazepines in trace amounts in wheat and potato.

Aqueous acid extracts of wheat grains and of potato tuber were found to contain a series of compounds displaying a high affinity to the central type benzodiazepine receptor (BZR) in mammalian brain. Further analysis using different HPLC systems, as well as mass spectrometry and gas chromatography combined with mass spectrometry lead to the identification of compounds belonging to the classical 5-phenyl-1,4-benzodiazepinones. In wheat grains diazepam, N-desmethyldiazepam, delorazepam, deschloro-diazepam, delormetazepam, lormetazepam and isodiazepam were identified, while potato tuber contained diazepam, N-desmethyldiazepam, delorazepam, lorazepam and delormetazepam. The concentration of the benzodiazepines (BZ) was in the low ppb range. Their biosynthesis most probably takes place in the plant tissue. The availability of BZs in plant nutritives points to a possible source for the previously reported presence of BZ in brain and peripheral tissues of several animal species and man.

Diazepam and N-desmethyldiazepam are found in rat brain and adrenal and may be of plant origin.

Benzodiazepine-binding inhibitory (BBI) activity was detected in aqueous extracts of brain and peripheral tissues of rats. The BBI activity in brain and in adrenals was, at least partially, due to the presence of N-desmethyldiazepam and diazepam as shown by HPLC, UV-spectroscopy and mass spectrometry. In addition, BBI activity was found in standardized rat food, as well as in a variety of cereals and in other nutritive plant products. In wheat grains diazepam and N-desmethyldiazepam could be identified by HPLC and analysis by gas chromatography combined with mass spectrometry. The estimated amounts of the two benzodiazepines present in rat brain and adrenals and in wheat grains were in the low ppb range. Since laboratory contamination was rigorously excluded we conclude that diazepam and N-desmethyldiazepam are naturally occurring compounds. These findings may explain their occurrence in the brain and adrenals of animals.

Increase of circulating beta-endorphin-like immunoreactivity correlates with the change in feeling of pleasantness after running.

Twenty-one male regular long distance runners participated in two 10 km runs one week apart. Their beta-endorphin-like immunoreactivity (beta-EIR) was assayed in plasma before and immediately after running. Mood was monitored by an adjective check list (Eigenschaftswörterliste, EWL) pre- and post-run. beta-EIR was significantly elevated post-run. Self-reliance and good mood scored higher after running. Both mood elevation and plasma beta-EIR increase showed a considerable individual variability but there was a significant correlation in the mean values of the two runs between individual beta-EIR increases (delta beta-EIR) and the changes of ratings in feeling of pleasantness (delta FP). High delta beta-EIR corresponded to positive mood change post-run.

Endogenous benzodiazepine receptor agonist in human and mammalian plasma.

Using ultra-filtration steps and HPLC-separation, a low molecular weight ligand of the benzodiazepine receptor was isolated from plasma of various mammalian species including man. The endogenous ligand acts on benzodiazepine receptors agonistically and apparently has a receptor affinity similar to Diazepam. The ligand is not identical with Diazepam as indicated by HPLC and UV-spectroscopy.

Polypeptide antigens of the synaptic plasma membranes of the rat brain.

Antisera to two groups of polypeptides isolated from central nervous system synaptic plasma membranes of mature rats, were used to study antigenic polypeptides of new born and adult rats. Immunoprecipitation and acrylamide gel electrophoretic analysis demonstrated greater amounts of antigenic polypeptides in adult rats. These antigenic polypeptides may be involved in synaptogenesis.

Antagonistic effect of L-aspartic acid on decrease in body weight, and food and fluid intake, and naloxone reversible rectal temperature depression caused by D-aspartic acid.

Seventy-five rats, divided into five groups, were given D-aspartic acid (D-Asp), L-Asp and D + L-Asp in ratio 1/1 or 1/2 for one week. The body weight, food and fluid intakes, and rectal temperature of the rats received D-Asp or D + L-Asp in 1/1 ratio significantly decreased. The decrease in rectal temperature was antagonized by naloxone. L-Asp given together with D-Asp in 1/2 ratio prevented D-Asp-caused decrease in body weight, food and fluid intakes, and rectal temperature. Although D-amino acids, as antipeptidases have some effects through endorphinergic systems, D-Asp (an inhibitor of L-asparaginase) seems to act at the level of L-asparaginase presumably by increasing the level of endorphins since L-Asp antagonizes the inhibitory effect of both D-Asp and morphine.

The effects of D- and/or L-aspartic acids on the total weight of body, the weights of certain organs, and their protein, triglyceride and glycogen content.

125 rats which were divided into five groups were deprived of food or given orally D- (a potent inhibitor for L-asparaginase) and/or L-aspartic acids (Asp) for one week. The body weights before and at the end of the experiment were determined as well as post mortem the weights of brain, liver and kidneys, their protein contents, and the liver triglyceride and glycogen contents. D- and D+L-Asp caused significant decreases in the weights of body and liver, and in daily fluid intake; in addition liver and kidney protein, and liver triglyceride and glycogen contents were found to be lower than control. On the other hand, the food-deprived group which was subjected to more or less the same body weight loss due to food deprivation showed only a decrease in the liver triglyceride content. Since D-amino acids cause naloxone reversible analgesia which is, thus, considered as an involvement of endorphinergic system and of vasopressin, the effects of D-Asp were attributed to the changes in the availability of opioids and vasopressin, which simultaneously have an effect on each other as well as an effect of the release of ACTH. L-Asp appeared to antagonize the effects of D-Asp. Because L-Asp antagonizes the acute and chronic effects of morphine, including that on L-asparaginase activity, the hypothesis is proposed that the antagonizing effects of L-Asp observed may be caused at the level of L-asparaginase activity.

Immunochemical evidence for exocytosis in isolated chromaffin cells after stimulation with depolarizing agents.

After chemical stimulation with depolarizing agents (Ba2+ or Ca2+/carbachol) isolated living chromaffin cells display a drastically increased binding capacity for anti-DBH, distributed spotwise on or near the outer cell membrane. This effect is inhibited by noradrenaline; it is not evoked by the non-exocytotically releasing agents tyramine and reserpine. the effect of apparent externalization of DBH is paralleled by the observation of a DBH-dependent binding of 125I-labelled protein A upon the same depolarizing stimuli. These observations are discussed as possible evidence for exocytotic activities.