Accumulation of pest insects on eucalyptus in California: random process or smoking gun

Eucalyptus spp., native to Australia, have been introduced into many parts of the world as important timber and ornamental trees. Although the trees have important silvicultural qualities, they also have generated intense dissatisfaction, particularly among groups of individuals in California. The trees have benefited from the lack of insect pests and diseases in their adventive ranges but that has changed over the past four decades. In California, two species of insect herbivores were introduced between the time trees were first introduced to the state in the middle of the 19th century and 1983. Between 1983 and 2008, an additional 16 Australian insect pests of eucalyptus have become established in the state. The modes or routes of introduction have never been established. However, examinations of different temporal and spatial patterns suggest that the introductions were nonrandom processes. It is possible that they occurred because of increased trade or movement of people, but the hypothesis that there were intentional introductions also must be considered. The rapid accumulation of introduced herbivores on an ornamental plant system in a single state is a cautionary example of what could happen if a major food or fiber crop were intentionally targeted.     

Mechanism of nicotine-induced pulmonary fibroblast transdifferentiation

We tested the hypothesis that in vitro nicotine exposure disrupts specific epithelial-mesenchymal paracrine signaling pathways and results in pulmonary interstitial lipofibroblast (LIF)-to-myofibroblast (MYF) transdifferentiation, resulting in altered pulmonary development and function. Studies were done to determine whether nicotine induces LIF-to-MYF transdifferentiation and to elucidate underlying molecular mechanism(s) involved and to determine whether nicotine-induced LIF-to-MYF transdifferentiation could be prevented by stimulating specific alveolar interstitial fibroblast lipogenic pathway. WI38 cells, a human embryonic pulmonary fibroblast cell line, were treated with nicotine with or without specific agonists of alveolar fibroblast lipogenic pathway, PTHrP, DBcAMP, or the potent PPARgamma stimulant rosiglitazone (RGZ) for 7 days. Expression of key lipogenic and myogenic markers was examined by RT-PCR, Western hybridization, and immunohistochemistry. The effect of nicotine on triglyceride uptake by WI38 cells and PTHrP binding to its receptor was also determined. Finally, the effect of transfecting WI38 cells with a PPARgamma expression vector on nicotine-induced LIF-to-MYF transdifferentiation was determined. Nicotine treatment resulted in significantly decreased expression of lipogenic and increased expression of myogenic markers in a dose-dependent manner, indicating nicotine-induced LIF-to-MYF transdifferentiation. This was accompanied by decreased PTHrP receptor binding to its receptor. The nicotine-induced LIF-to-MYF transdifferentiation was completely prevented by concomitant treatment with PTHrP, DBcAMP, RGZ, and by transiently overexpressing PPARgamma. Our data suggest nicotine induces alveolar LIF-to-MYF transdifferentiation through a mechanism involving downregulation of lipogenic PTHrP-mediated, cAMP-dependent PKA signaling pathway, which can be prevented using specific molecular targets. Potential therapeutic implications of these observations against in utero nicotine-induced lung injury remain to be tested.     

Characterization of nicotine-induced contraction in the canine bronchus

1. The modes of action of nicotine on the dog bronchial smooth muscle preparation was investigated, in order to compare with those on the bronchial preparations from the guinea-pig, rabbit and monkey. 2. Nicotine induced a contraction in the dog bronchial preparation, and this response was abolished by hexamethonium and atropine and potentiated by physostigmine. 3. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and due to the release of acetylcholine. 4. Tetrodotoxin did not inhibit the contractile response to nicotine in the dog bronchial preparation, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 5. The present observations in the dog bronchial preparations coincided with those in the rabbit and monkey bronchi but not with the findings in the guinea-pig bronchus.     

基因枪技术及其在基因治疗中的应用进展

目前基因转染载体主要分为病毒型载体和非病毒型载体,病毒载体虽转染率较高、表达时间长,但其安全性令人担忧,非病毒载体中基因枪的优势最为明显,临床化趋势最强。通过分析非病毒基因转染技术面临的障碍,介绍了基因枪技术的产生和原理及其显著的优势,并总结了当前基因枪技术在基因治疗中的应用,指出了基因枪技术发展面临的问题和发展方向。     

Stress-induced anorexia: implications for anorexia nervosa

Recent studies have suggested that stress may be a precipitating factor in the etiology of anorexia nervosa. The present paper examines the possible mechanisms involved in stress-induced anorexia and suggests how stress-induced changes in opiate systems, the hypothalamic-pituitary-adrenal axis and serotonergic systems may provide an explanation of many of the physiological and behavioral responses observed in anorexia nervosa. The present paper suggests that certain psychosocial and endocrinological factors may interact to provide the setting conditions for the syndrome. Finally, it is suggested that a dual therapeutic approach is required in that the syndrome needs to be treated both physiologically and psychologically to prevent relapse.     

Photothermal detection of nicotine-induced apoptotic effects in pancreatic cancer cells

The objective of this study was to evaluate the capability of a photothermal (PT) assay in determining the effects of graded doses of nicotine in a pancreatic acinar cell line (AR42J). The cellular response to nicotine was detected through the monitoring of PT signals from light-absorbing endogenous cellular structures that have been used as natural indicators for nicotine's action. It was demonstrated that introducing nicotine to cultured acinar cells in vitro leads to changes in cellular absorbing structures, thereby altering the microstructure of PT cell images and the temporal shape of PT signals. The results showed that the dependence of specific PT parameters was almost proportional to nicotine concentrations ranging from 1 nM to 100 μM, with the saturation maximum at and around 100 μM - 1 mM; thereafter, PT signals decreased rapidly to control levels and even lower, in the range of 1 - 50 mM. Conventional fluorescent tests (Annexin V - Propidium Iodide) performed in parallel showed no effect with nicotine at a concentration <1 μM (three orders of magnitude greater than the sensitivity threshold of the PT assay). With an increase in nicotine concentration from 1 mM to 50 mM, rapidly growing apoptotic and necrotic cells were detected. Thus, the PT assay demonstrated the capability for high-sensitivity detection of nicotine's impact, which may be related to a change in cell metabolism, apoptosis, or necrosis, depending on nicotine concentration.     

Role of nitric oxide in the nicotine-induced pituitary-adrenocortical response.

Nitric oxide (NO) is a major signaling molecule and biological mediator of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the role of NO formed by endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) in the stimulatory effect of nicotine on the HPA axis in rats under basal conditions. Also possible interaction of NOS systems with endogenous prostaglandins (PG) in that stimulation was assessed. NOS and cyclooxygenase inhibitors were administered i.p. 15 min prior to nicotine (2, 5 mg/kg i.p.). Plasma ACTH and serum corticosterone levels were measured 1 h after nicotine injection. NOS blockers given alone did not markedly affect the resting ACTH and corticosterone levels. L-NAME (2-10 mg/kg), a broad spectrum NOS inhibitor considerably and dose dependently enhanced the nicotine-induced ACTH and corticosterone secretion. L-NNA (2 mg/kg) and 7-nitroindazole (7-NI 20 mg/kg), neuronal NOS inhibitors in vivo also significantly augmented the nicotine-induced ACTH and corticosterone levels. L-arginine greatly impaired the nicotine-induced hormone responses and reversed the L-NNA elicited enhancement of the nicotine-evoked ACTH and corticosterone response. In contrast to the constitutive eNOS and nNOS antagonists, an inducible NOS antagonist guanethidine (50-100 mg/kg i.p.) did not substantially affect the nicotine-elicited pituitary-adrenocortical responses. Indomethacin (2 mg/kg i.p.), a non-selective cyclooxygenase blocker abolished the L-NAME and L-NNA-induced enhancement of the nicotine-evoked ACTH and corticosterone response. These results indicate that NO is an inhibitory mediator in the HPA axis activity. Inhibition of its generation by eNOS and nNOS significantly enhances the nicotine-induced HPA response. Under basal conditions iNOS is not involved in the nicotine-induced ACTH and corticosterone secretion. Prostaglandins play an obligatory role in the response of HPA axis to systemic nicotine administration.     

Ghrelin amplifies the nicotine-induced dopamine release in the rat striatum

The orexigenic peptide ghrelin plays a prominent role in the regulation of energy balance and in the mediation of reward mechanisms and reinforcement for addictive drugs, such as nicotine. Nicotine is the principal psychoactive component in tobacco, which is responsible for addiction and relapse of smokers. Nicotine activates the mesencephalic dopaminergic neurons via nicotinic acetylcholine receptors (nAchR). Ghrelin stimulates the dopaminergic neurons via growth hormone secretagogue receptors (GHS-R1A) in the ventral tegmental area and the substantia nigra pars compacta resulting in the release of dopamine in the ventral and dorsal striatum, respectively. In the present study an in vitro superfusion of rat striatal slices was performed, in order to investigate the direct action of ghrelin on the striatal dopamine release and the interaction of ghrelin with nicotine through this neurotransmitter release. Ghrelin increased significantly the dopamine release from the rat striatum following electrical stimulation. This stimulatory effect was reversed by both the selective nAchR antagonist mecamylamine and the selective GHS-R1A antagonist GHRP-6. Nicotine also increased significantly the dopamine release under the same conditions. This stimulatory effect was antagonized by mecamylamine, but not by GHRP-6. Ghrelin further stimulated the nicotine-induced dopamine release and this effect was abolished by mecamylamine and was partially inhibited by GHRP-6. The present results demonstrate that ghrelin stimulates directly the dopamine release and amplifies the nicotine-induced dopamine release in the rat striatum. We presume that striatal cholinergic interneurons also express GHS-R1A, through which ghrelin can amplify the nicotine-induced dopamine release in the striatum. This study provides further evidence of the impact of ghrelin on the mesolimbic and nigrostriatal dopaminergic pathways. It also suggests that ghrelin signaling may serve as a novel pharmacological target for treatment of addictive and neurodegenerative disorders.