Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

On the volume functional of compact manifolds with boundary with constant scalar curvature

We study the volume functional on the space of constant scalar curvature metrics with a prescribed boundary metric. We derive a sufficient and necessary condition for a metric to be a critical point, and show that the only domains in space forms, on which the standard metrics are critical points, are geodesic balls. In the zero scalar curvature case, assuming the boundary can be isometrically embedded in the Euclidean space as a compact strictly convex hypersurface, we show that the volume of a critical point is always no less than the Euclidean volume bounded by the isometric embedding of the boundary, and the two volumes are equal if and only if the critical point is isometric to a standard Euclidean ball. We also derive a second variation formula and apply it to show that, on Euclidean balls and ''small'' hyperbolic and spherical balls in dimensions 3 to 5, the standard space form metrics are indeed saddle points for the volume functional

Impulsive choice in mice lacking paternal expression of Grb10 suggests intragenomic conflict in behavior

Imprinted genes are expressed from one parental allele only as a consequence of epigenetic events that take place in the mammalian germ line and are thought to have evolved through intra-genomic conflict between parental alleles. We demonstrate, for the first time, oppositional effects of imprinted genes on brain and behavior. Specifically, here we show that mice lacking paternal Grb10 make fewer impulsive choices, with no dissociable effects on a separate measure of impulsive action. Taken together with previous work showing that mice lacking maternal Nesp55 make more impulsive choices this suggests that impulsive choice behavior is a substrate for the action of genomic imprinting. Moreover, the contrasting effect of these two genes suggests impulsive choices are subject to intra-genomic conflict and that maternal and paternal interests pull this behavior in opposite directions. Finally, these data may also indicate that an imbalance in expression of imprinted genes contributes to pathological conditions such as gambling and drug addiction, where impulsive behavior becomes maladaptive

Secretoneurin stimulates the production and release of luteinizing hormone in mouse L beta T2 gonadotropin cells

Secretoneurin (SN) is a functional secretogranin II (SgII)-derived peptide that stimulates luteinizing hormone (LH) production and its release in the goldfish. However, the effects of SN on the pituitary of mammalian species and the underlying mechanisms remain poorly understood. To study SN in mammals, we adopted the mouse LβT2 gonadotropin cell line that has characteristics consistent with normal pituitary gonadotrophs. Using radioimmunoassay and real-time RT-PCR, we demonstrated that static treatment with SN induced a significant increment of LH release and production in LβT2 cells in vitro. We found that GnRH increased cellular SgII mRNA level and total SN-immunoreactive protein release into the culture medium. We also report that SN activated the extracellular signal-regulated kinases (ERK) in either 10-min acute stimulation or 3-h chronic treatment. The SN-induced ERK activation was significantly blocked by pharmacological inhibition of MAPK kinase (MEK) with PD-98059 and protein kinase C (PKC) with bisindolylmaleimide. SN also increased the total cyclic adenosine monophosphate (cAMP) levels similarly to GnRH. However, SN did not activate the GnRH receptor. These data indicate that SN activates the protein kinase A (PKA) and cAMP-induced ERK signaling pathways in the LH-secreting mouse LβT2 pituitary cell line

On the topology and area of higher dimensional black holes

Over the past decade there has been an increasing interest in the study of black holes, and related objects, in higher (and lower) dimensions, motivated to a large extent by developments in string theory. The aim of the present paper is to obtain higher dimensional analogues of some well known results for black holes in 3+1 dimensions. More precisely, we obtain extensions to higher dimensions of Hawking's black hole topology theorem for asymptotically flat ($\Lambda=0$) black hole spacetimes, and Gibbons' and Woolgar's genus dependent, lower entropy bound for topological black holes in asymptotically locally anti-de Sitter ($\Lambda<0$) spacetimes. In higher dimensions the genus is replaced by the so-called $\sigma$-constant, or Yamabe invariant, which is a fundamental topological invariant of smooth compact manifolds.Comment: 15 pages, Latex2e; typos corrected, a convention clarified, resulting in the simplification of certain formulas, other improvement

Parabolic stable surfaces with constant mean curvature

We prove that if u is a bounded smooth function in the kernel of a nonnegative Schrodinger operator $-L=-(\Delta +q)$ on a parabolic Riemannian manifold M, then u is either identically zero or it has no zeros on M, and the linear space of such functions is 1-dimensional. We obtain consequences for orientable, complete stable surfaces with constant mean curvature $H\in\mathbb{R}$ in homogeneous spaces $\mathbb{E}(\kappa,\tau)$ with four dimensional isometry group. For instance, if M is an orientable, parabolic, complete immersed surface with constant mean curvature H in $\mathbb{H}^2\times\mathbb{R}$, then $|H|\leq 1/2$ and if equality holds, then M is either an entire graph or a vertical horocylinder.Comment: 15 pages, 1 figure. Minor changes have been incorporated (exchange finite capacity by parabolicity, and simplify the proof of Theorem 1)

A classification theorem for Helfrich surfaces

In this paper we study the functional \SW_{\lambda_1,\lambda_2}, which is the the sum of the Willmore energy, $\lambda_1$-weighted surface area, and $\lambda_2$-weighted volume, for surfaces immersed in $\R^3$. This coincides with the Helfrich functional with zero `spontaneous curvature'. Our main result is a complete classification of all smooth immersed critical points of the functional with $\lambda_1\ge0$ and small $L^2$ norm of tracefree curvature. In particular we prove the non-existence of critical points of the functional for which the surface area and enclosed volume are positively weighted.Comment: 21 page

Differentiation in Neuroblastoma: Diffusion-Limited Hypoxia Induces Neuro-Endocrine Secretory Protein 55 and Other Markers of a Chromaffin Phenotype

Background: Neuroblastoma is a childhood malignancy of sympathetic embryonal origin. A high potential for differentiation is a hallmark of neuroblastoma cells. We have previously presented data to suggest that in situ differentiation in tumors frequently proceeds along the chromaffin lineage and that decreased oxygen ( hypoxia) plays a role in this. Here we explore the utility of Neuro-Endocrine Secretory Protein 55 ( NESP55), a novel member of the chromogranin family, as a marker for this process.Methodology/Principal Findings: Immunohistochemical analyses and in situ hybridizations were performed on human fetal tissues, mouse xenografts of human neuroblastoma cell lines, and on specimens of human neuroblastoma/ganglioneuroma. Effects of anaerobic exposure on gene expression by cultured neuroblastoma cells was analyzed with quantitative real-time PCR. Fetal sympathetic nervous system expression of NESP55 was shown to be specific for chromaffin cell types. In experimental and clinical neuroblastoma NESP55 immunoreactivity was specific for regions of chronic hypoxia. NESP55 expression also correlated strikingly with morphological evidence of differentiation and with other chromaffin-specific patterns of gene expression, including IGF2 and HIF2 alpha. Anaerobic culture of five neuroblastoma cell lines resulted in an 18.9-fold mean up-regulation of NESP55.Conclusions/Significance: The data confirms that chronic tumor hypoxia is a key microenvironmental factor for neuroblastoma cell differentiation, causing induction of chromaffin features and NESP55 provides a reliable marker for this neuronal to neuroendocrine transition. The hypoxia-induced phenotype is the predominant form of differentiation in stroma-poor tumors, while in stroma-rich tumors the chromaffin phenotype coexists with ganglion cell-like differentiation. The findings provide new insights into the biological diversity which is a striking feature of this group of tumors