Modification by levo-propranolol of tremors induced by harmine in mice

Summary It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its antiserotonergic or anti-adrenergic property. The results indicated that 1- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Differences in cardiac myosin light chain LC1 among human,monkey and sheep

Summary The atrial and ventricular myosin light chains of human, monkey and sheep hearts were compared by dodecylsulfate polyacrylamide gel electrophoresis. The atrial light chain 2 and ventricular light chain 2 are similar among these mammals. However, the atrial light chain 1 of monkey has different electrophoretic mobility from those of human and sheep. The monkey ventricular light chain 1 has same mobility as that of sheep but different from that of human.Acknowledgments. This work was supported by MRC of Canada No. MA-8559. Dr G. Jackowski is a scholar of the Medical Research Council of Canada, and is the author to whom all correspondence should be addressed.     

JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport by activating kinesin-1

Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport. Finally, microtubule-binding and microfluidic chamber assays revealed that JIP1 and JIP3 cooperate to relieve kinesin-1 autoinhibition, which depends on the binding of JIP1 to kinesin-1 heavy chain (KHC) and light chain (KLC) and the binding of JIP3 to KLC and is essential for TrkB anterograde axonal transport and BDNF-induced TrkB retrograde signal. These findings could deepen our understanding of the regulation mechanism underlying TrkB anterograde axonal transport and provide a novel kinesin-1 autoinhibition-relieving model.     

川西亚高山针叶林生产力和光能利用效率研究现状

本文回顾了目前已发表的有关川西地区云冷杉林光能利用率的研究资料，从概念、测量方法、研究结果、影响因子等几个方面做了比较，发现川西地区森林净初级生产力和叶面积指数(LAI)的异质性很强。这种异质性使地面测量和遥感测量不能满足对小尺度川西亚高山针叶林生态系统结构和功能测定和预测的要求。基于形态和生理生态的模型方法由于具有机理性强，对参数变化反应灵敏，在时间和尺度上的灵活性将是未来研究川西亚高山针叶林群落生态系统过程和全球变化响应的重要手段。     

Modification by levo-propranolol of tremors induced by harmine in mice

It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its anti-serotonergic or anti-adrenergic property. The results indicated that l- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Regulation of the retinal interphotoreceptor matrix Na by the retinal pigment epithelium during the light response

We examined the rabbit retinal pigment epithelium (RPE) for Na transport properties which would allow it to buffer undesirable changes in Na concentrations in the interphotoreceptor matrix (IPM) during light and dark cycles. The RPE is selectivity permeable to sodium. Open and short circuit transport studies with RPE indicate a circulating (choroid to retina and back) Na current which does not compromise the electrical integrity of the blood brain barrier but together with the Na permeselectivity is of sufficient magnitude to buffer both upwards and downwards movements of IPM [Na] during light or dark responses.     

Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity

It is now well demonstrated that the repertoire of T cells includes not only cells that recognize specific MHC-presented peptide antigens, but also cells that recognize specific self and foreign lipid antigens. This T cell recognition of lipid antigens is mediated by a family of conserved MHC class I-like cell surface glycoproteins known as CD1 molecules. These are specialized antigen-presenting molecules that directly bind a wide variety of lipids and present them for T cell recognition at the surface of antigen-presenting cells. Distinct populations of T cells exist that recognize CD1-presented lipids of microbial, environmental or self origin, and these T cells participate in immune responses associated with infectious, neoplastic, autoimmune and allergic diseases. Here we review the current knowledge of the biology of the CD1 system, including the structure, biosynthesis and trafficking of CD1 molecules, the structures of defined lipid antigens and the types of functional responses mediated by T cells specific for CD1-presented lipids.     

Lysophosphatidylcholine induces cyclooxygenase-2-dependent IL-6 expression in human cardiac fibroblasts

Lysophosphatidylcholine (LysoPC) has been shown to induce the expression of inflammatory proteins, including cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), associated with cardiac fibrosis. Here, we demonstrated that LysoPC-induced COX-2 and IL-6 expression was inhibited by silencing NADPH oxidase 1, 2, 4, 5; p65; and FoxO1 in human cardiac fibroblasts (HCFs). LysoPC-induced IL-6 expression was attenuated by a COX-2 inhibitor. LysoPC-induced responses were mediated via the NADPH oxidase-derived reactive oxygen species-dependent JNK1/2 phosphorylation pathway, leading to NF-κB and FoxO1 activation. In addition, we demonstrated that both FoxO1 and p65 regulated COX-2 promoter activity stimulated by LysoPC. Overexpression of wild-type FoxO1 and S256D FoxO1 enhanced COX-2 promoter activity and protein expression in HCFs. These results were confirmed by ex vivo studies, where LysoPC-induced COX-2 and IL-6 expression was attenuated by the inhibitors of NADPH oxidase, NF-κB, and FoxO1. Our findings demonstrate that LysoPC-induced COX-2 expression is mediated via NADPH oxidase-derived reactive oxygen species generation linked to the JNK1/2-dependent pathway leading to FoxO1 and NF-κB activation in HCFs. LysoPC-induced COX-2-dependent IL-6 expression provided novel insights into the therapeutic targets of the cardiac fibrotic responses.     

Ga<Subscript>q</Subscript> proteins: molecular pharmacology and therapeutic potential

Seven transmembrane G protein-coupled receptors (GPCRs) have gained much interest in recent years as it is the largest class among cell surface receptors. G proteins lie in the heart of GPCRs signalling and therefore can be therapeutically targeted to overcome complexities in GPCR responses and signalling. G proteins are classified into four families (G_i, G_s, G_12/13 and G_q); G_q is further subdivided into four classes. Among them G_αq and G_αq/11 isoforms are most crucial and ubiquitously expressed; these isoforms are almost 88% similar at their amino acid sequence but may exhibit functional divergences. However, uncertainties often arise about G_αq and G_αq/11 inhibitors, these G proteins might also have suitability to the invention of novel-specific inhibitors for each isoforms. YM-254890 and UBO-QIC are discovered as potent inhibitors of G_αq functions and also investigated in thrombin protease-activated receptor (PAR)-1 inhibitors and platelet aggregation inhibition. The most likely G protein involved in PAR-1 stimulates responses is one of the G_αq family isoforms. In this review, we highlight the molecular structures and pharmacological responses of G_αq family which may reflect the biochemical and molecular role of G_αq and G_αq/11. The advanced understanding of G_αq and G_αq/11 role in GPCR signalling may shed light on our understanding on cell biology, cellular physiology and pathophysiology and also lead to the development of novel therapeutic agents for a number of diseases.