1,620 research outputs found

    Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

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    Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway

    Expression of gastrin-releasing peptide by excitatory interneurons in the mouse superficial dorsal horn

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    Background: Gastrin-releasing peptide (GRP) and its receptor have been shown to play an important role in the sensation of itch. However, although GRP immunoreactivity has been detected in the spinal dorsal horn, there is debate about whether this originates from primary afferents or local excitatory interneurons. We therefore examined the relation of GRP immunoreactivity to that seen with antibodies that label primary afferent or excitatory interneuron terminals. We tested the specificity of the GRP antibody by preincubating with peptides with which it could potentially cross-react. We also examined tissue from a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under control of the GRP promoter.<p></p> Results: GRP immunoreactivity was seen in both primary afferent and non-primary glutamatergic axon terminals in the superficial dorsal horn. However, immunostaining was blocked by pre-incubation of the antibody with substance P, which is present at high levels in many nociceptive primary afferents. EGFP+ cells in the GRP-EGFP mouse did not express Pax2, and their axons contained the vesicular glutamate transporter 2 (VGLUT2), indicating that they are excitatory interneurons. In most cases, their axons were also GRP-immunoreactive. Multiple-labelling immunocytochemical studies indicated that these cells did not express either of the preprotachykinin peptides, and that they generally lacked protein kinase CÎł, which is expressed by a subset of the excitatory interneurons in this region.<p></p> Conclusions: These results show that GRP is expressed by a distinct population of excitatory interneurons in laminae I-II that are likely to be involved in the itch pathway. They also suggest that the GRP immunoreactivity seen in primary afferents in previous studies may have resulted from cross-reaction of the GRP antibody with substance P or the closely related peptide neurokinin A

    Substance P-expressing excitatory interneurons in the mouse superficial dorsal horn provide a propriospinal input to the lateral spinal nucleus

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    The superficial dorsal horn (laminae I and II) of the spinal cord contains numerous excitatory and inhibitory interneurons, and recent studies have shown that each of these groups can be divided into several neurochemically distinct populations. Although it has long been known that some neurons in this region have intersegmental (propriospinal) axonal projections, there have been conflicting reports concerning the number of propriospinal cells and the extent of their axons. In addition, little is known about the neurochemical phenotype of propriospinal neurons or about the termination pattern of their axons. In the present study we show, using retrograde tracing, that around a third of lamina I–II neurons in the lumbar enlargement project at least five segments cranially. Substance P-expressing excitatory neurons are over-represented among these cells, accounting for one-third of the propriospinal neurons. In contrast, inhibitory interneurons and excitatory PKCγ neurons are both under-represented among the retrogradely labelled cells. By combining viral vector-mediated Cre-dependent anterograde tracing with immunocytochemistry, we provide evidence that the lateral spinal nucleus (LSN), rather than the superficial dorsal horn, is the main target for axons belonging to propriospinal substance P-expressing neurons. These findings help to resolve the discrepancies between earlier studies and have implications for the role of the LSN in pain mechanisms

    Book Reviews

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    The Economics of Biotechnology under Ecosystem Disruption

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    Economic analysis of chemical pesticide use has shown that the interactions between plants, pests, damage control technology and state of the ecosystem are important variables to be considered. Hence, a bio-economic model was developed for the assessment of Bt variety and pesticide-based control strategies of the cotton bollworm in China. The model simulates plant growth, the dynamics of pest populations and of natural enemies. The model predictions are used as major inputs for a stochastic partial budgeting procedure of alternative control strategies. Results show that: (1) productivity effects of Bt varieties and pesticide use depend on the action of natural control agents, and (2) the profitability of damage control measures increases with the severity of ecosystem disturbance. The findings highlight the importance of the choice of a counterfactual scenario in the assessment of the impact of agricultural biotechnology. Also, some doubts are raised whether the high benefits of Bt cotton varieties based on cross section comparisons are realistic.Research and Development/Tech Change/Emerging Technologies, Q57, Q55, O13, O3,

    Institutional Constraints for the Success of Agricultural Biotechnology in Developing Countries: The Case of Bt-Cotton in Shandong Province, China

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    The use of genetically engineered crop varieties has recently become one option to prevent pest damage in agriculture. The promoters of biotechnology stress the great potential for yield increase and pesticide reduction while the critics point out the potential risks for biodiversity and human health as well as institutional problems for implementation especially in developing countries. The objective of this paper is an in-depth economic analysis of Btcotton production in North East China under small-scale conditions and several years after technology introduction. Data were collected in 2002 (March - October) in Linqing County, a major cotton growing area of Shandong Province, China. Data collection comprised a seasonlong monitoring of Bt-cotton production with 150 farmers from five villages, and three complementary household interviews. In addition, plot-level biological testing was carried out to determine the actual Bt toxin concentration in the varieties that were used by the farmers. All farmers in the case study were growing insect resistant Bt-cotton varieties in 2002. Nevertheless, they sprayed high amounts of chemical pesticides that were almost entirely insecticides. A proportion of 40% of the pesticides applied belonged to the categories extremely or highly hazardous (WHO classes Ia and Ib). The paper reviews methodological issues inherent to impact assessment of crop biotechnology and identifies market and institutional failure as possible reasons for continued high pesticide use. The production function methodology with damage control function was applied and it was found that for both damage control inputs, i.e. Bt and insecticides the coefficients were not significantly different from zero. In contrast to studies that treat Bt varieties as dummy variable in economic models, in this research it was possible to specify Bt toxin concentration in cotton leaf samples as a continuous variable. The results of this study support the notion that introducing Biotechnology in developing countries without enabling institutions that assure proper use of the technology can considerably limit its benefits. Hence it is important to include institutional criteria in the evaluation of agricultural biotechnology especially in developing countries. --

    Ubuntu and the Struggle for Reason: Humaneness Beyond Humanism

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    Ubuntu and the Struggle for Reason: Humaneness Beyond Humanism Andrew Shaw (University of Washington) Comments by Ismael Gutierrez (Puget Sound) Chair: Emma Cole This paper examines how modern societies might begin to live by the African philosophy of ubuntu through the prominent example of the Truth and Reconciliation Commission in South Africa. Following the work of philosophers from perspectives of race and disability, I contend that the liberal conception of rational personhood continues to grapple with problems of exclusion and demonstrate the exigency of theorizing alternative modes of personhood. I then argue in support of ubuntu as a moral system and compare ubuntu with the liberal Kantian tradition. In particular, I hold that ubuntu presents a promising solution to the exclusion problem by viewing personhood as a flexible designation that must be earned through upstanding moral character. I thus find that ubuntu’s central notion of “be-ing becoming” presents a fundamental ontological difference with contemporary liberalism’s emphasis on rationality and autonomy
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