室间隔缺损ALK3下游相关基因的初步研究

了解ALK3在心脏发育中的作用,探索室间隔缺损的特异相关基因及其信号传导途径。应用α-MHC-Cre/lox P系统,建立了心脏ALK3基因敲除小鼠模型,利用PCR选择性cDNA差异显示法和基因芯片扫描(RNA microarray)的方法,比较对照组和试验组mRNA表达水平,筛选ALK3下游基因。对照组的mRNA来自α-MHC-Cre^+/-ALK3^F/＋的11.5d小鼠胚胎心脏,试验组的mRNA来自α-MHC-Cre^+/-ALK3^F/-的11.5d小鼠胚胎心脏。心脏特异的ALK3基因敲除后,血小板激活因子乙酰水解酶及转录因子Pax-8等基因的表达水平下降,β亚类14-3-3蛋白及蛋白酪氨酸激酶等基因的表达水平上调。血小板激活因子乙酰水解酶及转录因子Pax-8等基因可能是ALK3重要的下游基因,与室间隔缺损的形成有关;β亚类14-3-3蛋白及蛋白酪氨酸激酶等基因是骨形态形成蛋白信号传导途径的调控因子。     

Coordinate Expression of the Vesicular Acetylcholine Transporter and Choline Acetyltransferase Following Septohippocampal Pathway Lesions

Abstract: The gene for the vesicular acetylcholine transporter (VAChT) was recently cloned and found to be located within a 5' noncoding intron of the gene for choline acetyltransferase (ChAT). There appear to be several shared and unique promoters for each gene, suggesting that control of expression of these two genes can be either coordinated or independent. Two lesions, axotomy and immunotoxin, directed at the well defined septohippocampal cholinergic pathway were used to determine VAChT and ChAT protein expression in the degenerating terminal fields in the hippocampus and the cell bodies of the medial septum nucleus after injury. Two weeks after lesioning, decreases of up to 90% in VAChT were found in the affected hippocampus by immunoblotting and immunocytochemistry, similar to ChAT activity. The number of VAChT- and ChAT-immunopositive neurons in the medial septum decreased by up to 95%. Eight weeks following axotomy, the number of VAChT- and ChAT-immunopositive neurons had increased to almost 50% in fimbria-fornix-lesioned animals, indicating coordinate reexpression of both cholinergic markers in recovered neurons. There was no recovery of either VAChT or ChAT immunoreactivity after the irreversible immunotoxin lesions. Thus, with use of immunological techniques, there appears to be coordinate expression of VAChT and ChAT in the septohippocampal pathway following either unilateral fimbria-fornix or bilateral immunotoxin lesion.     

Ependymal and neuronal specializations in the lateral ventricle of the Pekin duck,Anas platyrhynchos

Summary The lateral ventricles of the Pekin duck, Anas platyrhynchos, display characteristic ependymal and hypendymal specializations. Adjacent to the nucleus accumbens and the basal pole of the lateral septum the ventricular surface shows a highly folded pattern either with protrusions into the ventricular lumen or deep invaginations into the brain tissue. These medial and basal ependymal folds are found exclusively in a circumscribed region extending over a range of 600 m in the rostrocaudal direction. Ependymal folds occurring in the lateral wall of the ventricles were traced up to the level of the interventricular foramen. Numerous capillaries are observed in the subependymal layer of these folds.By means of immunocytochemistry with antibodies against chicken vasoactive intestinal polypeptide (VIP) an aggregation of classical cerebrospinal fluid-contacting neurons is shown in the region of the nucleus accumbens and the lateral septum. These neurons are closely related to the ependymal folds. Additional VIP-immunoreactive neurons are scattered in deeper layers of the lateral septum and the nucleus accumbens. The latter are richly innervated by VIP-immunoreactive nerve fibers.The results of the present study are discussed with particular reference to the hypothesis of Kuenzel and van Tienhoven (1982) that ependymal specializations demonstrated in the lateral ventricles of the domestic fowl might represent a new circumventricular organ (lateral septal organ).The authors are greatly indebted to Professor A. Oksche for stimulating discussionsSupported by the Deutsche Forschungsgemeinschaft (Ko 758/2-2; 2-3) and the P. Carl Petersen Foundation     

Interspecific perspective on mechanical and nonmechanical models of primate circumorbital morphology.

Linear dimensions and angular orientations of the browridge, postorbital bar, and postorbital septum were obtained from a representative series of primates and compared with variables associated with several nonmechanical and biomechanical/mechanical models put forward to explain the form and function of the circumorbital region. Analyses of the results indicate that face size is the primary determinant of variation in primate circumorbital morphology. Anteroposterior browridge thickness is correlated with neural-orbital disjunction among anthropoid primates, but not among prosimians. This difference appears related to differences in the construction of the upper face and anterior cranial fossa between prosimians and anthropoids. Little support is demonstrated for the anterior dental loading model of browridge development. Mediolateral postorbital bar width and (to a lesser degree) browridge height are correlated with neurofacial torsion during mastication and variation in masticatory muscle size. These analyses further suggest that since circumorbital structures (especially the browridges) are located the farthest away from the chewing apparatus, they are least affected by masticatory stresses.     

On the separation of functions mediated by the AV3V region

Knife-cuts were used to separate the disruptive effects on fluid balance that are produced by electrolytic lesions of the anteroventral third ventricle (AV3V) region. It was observed that vertical cuts of the dorsal stalk of the subfornical organ (SFO) produced none of these effects. Horizontal cuts between the SFO and the anterior commissure produced neither of the acute effects of AV3V lesions (adipsia and diuretic weight loss) but they did mimic AV3V lesions in disrupting drinking responses to peripherally injected angiotensin and hypertonic saline. In contrast, horizontal cuts between the anterior commissure and the organum vasculosum of the lamina terminalis (OVLT) did not reduce drinking responses to angiotensin but they did cause a large weight loss during the 24 hours following surgery. It is suggested that these ventral cuts severed neural connections between the medial septum and the ventral medial preoptic area in producing the large weight loss. Together with findings from other experiments, these findings support the hypothesis that distinct neural elements mediate the various functions that are disrupted by lesions of the AV3V region.     

Regulation of cholinergic gene expression by nerve growth factor depends on the phosphatidylinositol-3'-kinase pathway

Nerve growth factor (NGF) exerts anti-apoptotic, trophic and differentiating actions on sympathetic neurons and cholinergic cells of the basal forebrain and activates the expression of genes regulating the synthesis and storage of the neurotransmitter acetylcholine (ACh). We have been studying the intracellular signaling pathways involved in this process. Although, in the rat pheochromocytoma cell line PC12, NGF strongly activates the mitogen-activated protein kinase (MAPK) pathway, prolonged inhibition of MAPK kinase (MEK) activity by PD98059 or U0126 did not affect the ability of NGF to up-regulate choline acetyltransferase (ChAT) or to increase intracellular ACh levels. In contrast, the treatment with the phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002, but not with its inactive analogue LY303511, completely abolished the NGF-induced production of ACh. Inhibition of PI3K also eliminated the NGF effect on the intracellular ACh level in primary cultures of septal neurons from E18 mouse embryos. Blocking the PI3K pathway prevented the activation of cholinergic gene expression, as demonstrated in RT/PCR assays and in transient transfections of PC12 cells with cholinergic locus promoter-luciferase reporter constructs. These results indicate that the PI3K pathway, but not the MEK/MAPK pathway, is the mediator of NGF-induced cholinergic differentiation.     

Mechanical significance of ammonoid septa with complex sutures

Pre- and post-19th century hypotheses relating hydrostatic pressure to the mechanical function of sutural complexity are compared. The old ideas gave rise to the 19th century 'Buckland hypothesis', which is in turn largely synonymous with the 'Westermann model'. Buckland (1836) postulated that fluted septa buttressed the weak flanks of the phragmocone wall. Two new parameters are introduced to define the covariation between the strength of cylindrical segments of the wall flank bounded by the distance between adjacent lobe and saddle-flutes in transverse sections. The product of the index of wall strength (IWS) and this inverse support angle (ISA) predicts the buckling pressure in a cylinder of infinite length, and it implies that coiled nautiloids were more likely to be imploded via their whorl flanks than the apparently weaker oxyconic ammonoids. The widely used index of sutural complexity (ISC) measures the marginal corrugation which obscures this trend and acts as an elastic bed for both strong and weak walls. However, the ISC is more proportional to habitat depth than the buckling pressure when all other factors are constant. The central thickness of each fluted septum was increased in direct proportion to the distance spanned by the septum and the hydrostatic pressure on it in the 'last septum' position. The marginal thickness was maintained at a more constant value, which permitted the suture to increasingly act like a spring or shock absorber, as the wall thickness was enlarged during ontogeny. Both the ratios, between the central and marginal thicknesses and the closely related ISC, therefore, increased with shell diameter and habitat depth.     

八种野豌豆属植物的核型研究

本文研究了八种野豌豆的核型,并首次报道了长尖野豌豆的染色体数目及其核型和新疆野豌豆的核型。同时提出了野豌豆属核型进化的两种趋势:原始基数的减少,从x=7→x=6→x=5;从多年生进化到一年生,核型的不对称性也随之增加。