Control of endodermal endocrine development by Hes-1

Development of endocrine cells in the endoderm involves Atonal and Achaete/Scute-related basic helix-loop-helix (bHLH) proteins. These proteins also serve as neuronal determination and differentiation factors, and are antagonized by the Notch pathway partly acting through Hairy and Enhancer-of-split (HES)-type proteins. Here we show that mice deficient in Hes1 (encoding Hes-1) display severe pancreatic hypoplasia caused by depletion of pancreatic epithelial precursors due to accelerated differentiation of post-mitotic endocrine cells expressing glucagon. Moreover, upregulation of several bHLH components is associated with precocious and excessive differentiation of multiple endocrine cell types in the developing stomach and gut, showing that Hes-1 operates as a general negative regulator of endodermal endocrine differentiation.     

Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate

As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H(13)CO(3)(-)) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3)(-). The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients, we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.     

急性肝功能衰竭的猪动物模型

目的：建立一个比较接近人类条件的急性肝衰竭模型。用于人工肝脏治疗的疗效和安全性的测试。方法：以右旋半乳糖来制造猪肝衰竭的大型动物模型,分组３组给药,剂量分别为０．５、１和０．７５g/kg。观察其临床表现、生理生化指标和病理改变。结果：３组实验都能引出与人的临床和生化指标变化相伫的肝功能衰竭的表现,以０．７５g/kg组最为理想。结论：以０．７５g/kg的半乳糖胺制造的急性肝功能衰竭的猪动物模型,符合人工肘脏研究对动物模型的要求。     

Freshwater harpacticoids (Crustacea: Copepoda: Harpacticoida) in Norway – a comprehensive contribution from G.O. Sars,and a provisional checklist

Since the pioneering works of the Norwegian biologist G.O. Sars, little attention has been given to the freshwater harpacticoids in Norway. The prime purpose of this paper is to present the state of current knowledge about the Norwegian freshwater harpacticoid fauna based on all known published and unpublished literature and archive material. We highlight the contribution of G.O. Sars to the knowledge of this group by presenting his remaining unpublished archive material. We present two Norwegian species checklists – one for freshwater harpacticoids (16 species) and another for freshwater-associated/brackish-water harpacticoids (nine species). Four of the freshwater harpacticoid species are described by G.O. Sars. Original unpublished plates with drawings of those species are included in the paper. In addition, an overview of species distributions throughout the country is given.     

Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family.

Structural comparison of the major envelope glycoproteins (gp70) from 35 different murine type C viruses and free gp70 expressed at various anatomical sites in the mouse showed that the gp70s are polymorphic products of a large multi-gene family encoding viral and differentiation antigens. Different proviruses are expressed in cells following distinct pathways of differentiation. When the various gp70s are grouped according to primary structure they fall naturally into viral host range classes, confirming the suspicion that C-type viral tropism is largely determined by the nature of the gp70 product expressed.     

Using wavelets to obtain a consistent ordinary least squares estimator of the long‐memory parameter

We develop an ordinary least squares estimator of the long‐memory parameter from a fractionally integrated process that is an alternative to the Geweke and Porter‐Hudak (1983) estimator. Using the wavelet transform from a fractionally integrated process, we establish a log‐linear relationship between the wavelet coefficients' variance and the scaling parameter equal to the log‐memory parameter. This log‐linear relationship yields a consistent ordinary least squares estimator of the long‐memory parameter when the wavelet coefficients' population variance is replaced by their sample variance. We derive the small sample bias and variance of the ordinary least squares estimator and test it against the GPH estimator and the McCoy–Walden maximum likelihood wavelet estimator by conducting a number of Monte Carlo experiments. Based upon the criterion of choosing the estimator which minimizes the mean squared error, the wavelet OLS approach was superior to the GPH estimator, but inferior to the McCoy–Walden wavelet estimator for the processes simulated. However, given the simplicity of programming and running the wavelet OLS estimator and its statistical inference of the long‐memory parameter we feel the general practitioner will be attracted to the wavelet OLS estimator. Copyright © 1999 John Wiley & Sons, Ltd.     

Investigating metal-binding in proteins by nuclear magnetic resonance

Metal ions play a key role for the function of many proteins. The interaction of the metal ion with the protein and its involvement in the function of the protein vary widely. In some proteins, the metal ion is bound tightly to the ligand residues and may be the key player in the function of the protein, as in the case of blue copper proteins. In other proteins, the metal ion is bound only temporarily and loosely to the protein, as in the case of some metalloenzymes and other proteins where the metal ion acts as a cofactor necessary for the function of the protein. Such proteins are often known as metal ion-activated proteins. The review focuses on recent nuclear magnetic resonance (NMR) studies of a series of metal-dependent proteins and the characterization of the metal-binding sites. In particular, we focus on NMR techniques for studying metal binding to proteins such as chemical shift mapping, paramagnetic NMR and changes in backbone dynamics upon metal binding. Received 12 October 2006; received after revision 30 November 2006; accepted 5 February 2007     

Prevalence of Elaeophora schneideri and Onchocerca cervipedis in mule deer from central Utah

Thirteen of 265 deer (4.9 percent) from central Utah were positive for Elaeophora schneideri, and 180 (67.9 percent) were infected with Onchocerca cervipedis. The rate of infection for E. schneideri and O. cervipedis increased significantly with age of the host (chi - square of 17.5 and 15.5, respectively, p