In vivo release of dopamine during perfusion of neurotensin in substantia nigra of the unrestrained rat

The functional effect of neurotensin on the kinetics of dopamine (DA) release in the substantia nigra of the freely moving rat was investigated. After guide tubes for push-pull perfusion were implanted stereotaxically just above the substantia nigra, endogenous stores of DA in this structure were labelled by micro-injection of 0.02–0.05 μCi of [¹⁴C]-DA. Then an artificial cerebrospinal fluid (CSF) was perfused within the site at a rate of 20 μl/min at successive 5 min intervals. Neurotensin added to the CSF perfusate in concentrations of 0.05–0.1 μg/μl evoked an immediate, Ca⁺⁺ dependent release of DA from sites directly within the substantia nigra or a delayed efflux when the peptide was perfused at the edge of this structure. Neurotensin failed to affect the pattern of release of this monoamine at sites which were not within the substantia nigra. Further, the body temperature of the rat also was not altered by neurotensin at any of the sites of perfusions. A relatively inactive analogue of the peptide, [D-Arg]⁹ neurotensin, was essentially without effect on DA activity. In double isotope experiments in which the substantia nigra of the rat was labelled with both [³H]-5-HT and [¹⁴C]-DA, the perfusion with neurotensin failed to affect 5-HT efflux while the release of DA was enhanced. Chromatographic analysis of the metabolites of DA in samples of push-pull perfusates revealed that neurotensin enhanced significantly the level of DOPAC and HVA. Overall, these results demonstrate that in the unrestrained rat neurotensin acts selectively within the substantia nigra to alter the presynaptic, Ca⁺⁺ dependent release of DA. It is suggested that the mechanism by which the tri-decapeptide functions within this brainstem structure is through its modulation of nigral dopaminergic neurons.     

Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats

Although endogenous cannabinoid systems have been implicated in the modulation of the rewarding effects of abused drugs and food, little is known about the direct effects of endogenous ligands for cannabinoid receptors on brain reward processes. Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans. Anandamide produced two distinctly different effects on dopamine levels: (1) a rapid, transient increase that was blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade. Both effects were blocked by infusing either tetrodotoxin (TTX, 1 microm) or calcium-free Ringer's solution through the microdialysis probe, demonstrating that they were dependent on the physiologic activation of dopaminergic neurotransmission. Thus, these results indicate that anandamide, through the activation of the mesolimbic dopaminergic system, participates in the signaling of brain reward processes.     

U7 snRNAs： A Computational Survey

U7 small nuclear RNA (snRNA) sequences have been described only for a handful of animal species in the past. Here we describe a computational search for func- tional U7 snRNA genes throughout vertebrates including the upstream sequence elements characteristic for snRNAs transcribed by polymerase Ⅱ. Based on the results of this search, we discuss the high variability of U7 snRNAs in both se- quence and structure, and report on an attempt to find U7 snRNA sequences in basal deuterostomes and non-drosophilids insect genomes based on a combination of sequence, structure, and promoter features. Due to the extremely short se- quence and the high variability in both sequence and structure, no unambiguous candidates were found. These results cast doubt on putative U7 homologs in even more distant organisms that are reported in the most recent release of the Rfam database.     

Nicotinic Receptor-Mediated Release of Noradrenaline in the Human Neuroblastoma SH-SY5Y

Abstract: Dimethylphenylpiperazinium iodide (a nicotinic agonist) evokes noradrenaline release from human neuroblastoma SH-SY5Y cells that have been pretreated with 12- O -tetradecanoylphorbol 13-acetate for 8 min. This effect of dimethylphenylpiperazinium iodide was inhibited by 1 μ M mecamylamine but not by 1 μ M atropine, which suggests that SH-SY5Y cells express nicotinic receptors coupled to the release of noradrenaline. Dimethylphenylpiperazinium iodide-evoked release was enhanced by 5 μ M Bay K 8644 (an L-type calcium agonist) and inhibited by 1 μ M nifedipine. Dimethylphenylpiperazinium iodide depolarised SH-SY5Y cells and enhanced the level of intracellular calcium in cells loaded with fura 2. The effects of dimethylphenylpiperazinium iodide on noradrenaline release, depolarisation, and intracellular calcium levels were all inhibited by 1 μ M desmethylimipramine. The results of this study show that nicotinic receptors in SH-SY5Y cells stimulate noradrenaline release by activation of L-type calcium channels.     

Tree-ring-based disturbance reconstruction in interdisciplinary research: Current state and future directions

Disturbances play an important role in forest dynamics. The determination of long-term spatiotemporal characteristics of disturbance regimes is essential for understanding forest dynamics and its shifts under global changes. Tree rings are known to provide detailed insight into both temporal and spatial patterns of forest disturbance history. One of the most commonly used indirect tree-ring techniques for investigating past disturbances is growth release detection (GRD), i.e. the abrupt radial growth increase of trees as a reaction to improved light conditions after the death of a disturbed neighbouring canopy tree or trees. However, there are several issues which have not been addressed so far. Here, an overview of GRD and guide for researchers aiming to incorporate GRD into their research is provided, with focus on conventional running mean methods. The aim is to cover various issues of the GRD procedure such as sampling strategy and data quality, selection of appropriate methods and parameter settings, suggested analysis procedures as well as result presentation. Overall, the importance of GRD incorporation in multidisciplinary studies of forest dynamics is highlighted, as it offers a precise tool for gathering long-term information about past disturbances. Lastly, this paper also suggests several future challenges focused on possible utilization of GRD in mainstream ecology to answer long-standing global ecological questions and improve understanding of past processes in forest ecosystems.     

Synthesis and biological evaluation of a novel photo-activated histone deacetylase inhibitor

Hydroxamic acid-based histone deacetylase inhibitors (HDACi) are a class of epigenetic agents with potentially broad therapeutic application to several disease states including post angioplasty mediated neointimal hyperplasia (NIH). Precise spatiotemporal control over the release of HDACi at the target blood vessel site is required for the safe and successful therapeutic use of HDACi in the setting of drug eluting balloon catheter (DEBc) angioplasty treatment of NIH. We aimed to develop and characterise a novel photoactive HDACi, as a potential coating agent for DEBc.Metacept-3 1 was caged with a photo-labile protecting group (PPG) to synthesise a novel UV365nm active HDACi, caged metacept-3 15. Conversion of caged metacept-3 15 to active/native metacept-3 1 by UV365nm was achievable in significant quantities and at UV365nm power levels in the milliwatt (mW) range.In vitro evaluation of the biological activity of pre and post UV365nm activation of caged metacept-3 15 identified significant HDACi activity in samples exposed to short duration, mW range UV365nm. Toxicity studies performed in human umbilical vein endothelial cells (HUVEC’s) identified significantly reduced toxicity of caged metacept-3 15 pre UV365nm exposure compared with native metacept-3 1 and paclitaxel (PTX).Taken together these findings identify a novel photo-activated HDACi, caged metacept-3 15, with pharmacokinetic activation characteristics and biological properties which may make it suitable for evaluation as a novel coating for targeted DEBc angioplasty interventions.     

Chinese plasma-derived products supply under the lot release management system in 2007–2011

In 2007, the Chinese State Food and Drug Administration (SFDA) implemented a management system for lot release of all plasma-derived products. Since then, there have been only a few systematic studies of the blood supply, which is a concern when considering the small amount of plasma collected per capita (approximately 3 L/1000 people). As a result, there may be a threat to the safety of the available blood supply. In this study, we examined the characteristics of the supply of Chinese plasma-derived products. We investigated the reports of lot-released biological products derived from all 8 national or regional regulatory authorities in China from 2007 to 2011. The market supply characteristics of Chinese plasma-derived products were analyzed by reviewing the changes in supply varieties, the batches of lot-released plasma-derived products and the actual supply. As a result, the national regulatory authorities can more accurately develop a specific understanding of the production and quality management information provided by Chinese plasma product manufacturers. The implementation of the lot release system further ensures the clinical validity of the plasma-derived products in China and improves the safety of using plasma-derived products. This work provides an assessment of the future Chinese market supply of plasma-derived products and can function as a theoretical basis for the establishment of hemovigilance.     

Reactions of Adriamycin with Microsomal Iron and Lipids

Iron plays a central role in oxidative injury, reportedly because it catalyzes superoxide- and hydrogen peroxide-dependent reactions yielding a powerful oxidant such as the hydroxyl radical. Iron is also thought to mediate the cardiotoxic and antitumour effects of adriamycin and related compounds. NADPH-supplemented microsomes reduce adriamycin to a semiquinone radical, which in turn re-oxidizes in the presence of oxygen to form superoxide and hence hydrogen peroxide. During this redox cycling membrane-bound nonheme iron undergoes superoxide dismutase- and catalase-insensitive reductive release. Membrane iron mobilization triggers lipid peroxidation, which is markedly enhanced by simultaneous addition of superoxide dismutase and catalase. The results indicate that : i) lipid peroxidation is mediated by the release of iron, yet the two reactions are governed by different mechanisms; and ii) oxygen radicals are not involved in or may actually inhibit adriamycin-induced lipid peroxidation. Microsomal iron delocalization and lipid peroxidation might represent oxyradical-independent mechanisms of adriamycin toxicity.     

DNA repair mechanisms in dividing and non-dividing cells

DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.     

Establishment,spread, and impact of an invasive planthopper on its invasive host plant: Prokelisia marginata (Homoptera: Delphacidae) exploiting Spartina anglica (Poales: Poaceae) in Britain

1. Since its recent arrival in Britain, the planthopper Prokelisia marginata has spread widely around saltmarshes on the east and south coast of England and south Wales, feeding on Common Cordgrass, Spartina anglica, itself an invasive non-native species. 2. Results suggest that P. marginata populations in Britain benefit from a degree of natural enemy release. No evidence of parasitism was found in over 71 000 eggs, nymphs, and adults inspected. The only potential natural enemy control was suggested by a positive correlation between the densities of planthoppers and generalist spiders. 3. Experimental exposure under both glasshouse and field conditions to typical field densities of planthoppers resulted in significant negative effects on a number of host plant performance metrics. 4. Spartina anglica is important for stabilising estuarine sediments and has been deliberately planted for this purpose in the past. Its weakening as a result of heavy planthopper herbivory could have serious consequences for the long-term stability of Britain's vulnerable saltmarsh habitats.