Development and differentiation of the intestinal epithelium

The gastrointestinal tract develops from a simple tube to a complex organ with patterns of differentiation along four axes of asymmetry. The organ is composed of all three germ layers signaling to each other during development to form the adult structure. The gut epithelium is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial cells are required for normal orderly development/differentiation, homeostasis, and apoptosis. Embryonically important patterning factors are used during adult stages for these processes. Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Wnt systems are used both in embryologic and adult times of gut development. We focus on and review the roles of these factors in gut epithelial cell development and differentiation.Received 18 October 2002; received after revision 18 December 2002; accepted 18 December 2002     

Deep roots of the Messinian salinity crisis

The Messinian salinity crisis--the desiccation of the Mediterranean Sea between 5.96 and 5.33 million years (Myr) ago--was one of the most dramatic events on Earth during the Cenozoic era. It resulted from the closure of marine gateways between the Atlantic Ocean and the Mediterranean Sea, the causes of which remain enigmatic. Here we use the age and composition of volcanic rocks to reconstruct the geodynamic evolution of the westernmost Mediterranean from the Middle Miocene epoch to the Pleistocene epoch (about 12.1-0.65 Myr ago). Our data show that a marked shift in the geochemistry of mantle-derived volcanic rocks, reflecting a change from subduction-related to intraplate-type volcanism, occurred between 6.3 and 4.8 Myr ago, largely synchronous with the Messinian salinity crisis. Using a thermomechanical model, we show that westward roll back of subducted Tethys oceanic lithosphere and associated asthenospheric upwelling provides a plausible mechanism for producing the shift in magma chemistry and the necessary uplift (approximately 1 km) along the African and Iberian continental margins to close the Miocene marine gateways, thereby causing the Messinian salinity crisis.     

气固流态化动态特征的模拟

运用基于硬球理论的离散型模型模拟了气固流态化的基本特征，观察了操作条件对鼓泡流化的影响。其模拟结果表明：1.气体通过分布板后形成许多气泡。最初，这些气泡以较小的尺寸形成在孔口，然后逐渐长大并上升。当气泡到达床层表面而破裂时，导致了床层表面的波动。2.床层中的压降随着气体速度和气体分布板中孔数的增加而增加。从而增加气体速度和分布板孔数将产生更多的气泡，并改进颗粒间的混合程度。3.与国际上现有离散型模型相比，基于颗粒运动分解思想的硬球模型更为真实、更为简单。它能够定性而形象地复现气固流化系统的实验特征，为实验预测提供辅助的研究方法。     

Apolipoprotein-mediated pathways of lipid antigen presentation

Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens.     

Cyclin D control of growth rate in plants

The mechanisms by which plants modulate their growth rate in response to environmental and developmental conditions are unknown, but are presumed to involve specialized regions called meristems where cell division is concentrated. The possible role of cell division in influencing meristem activity and overall plant growth rate is controversial, with a prevailing view that cell division is secondary to higher order meristem controls. Here we show that a reduction in the length of the cell-cycle G1 phase and faster cell cycling occur when the rate of cell division in transgenic tobacco plants is increased by the plant D-type cyclin CycD2 (ref. 8). The plants have normal cell and meristem sizes, but elevated overall growth rates, an increased rate of leaf initiation and accelerated development in all stages from seedling to maturity. We conclude that cell division is a principal determinant of meristem activity and overall growth rate, and propose that modulation of plant growth rate is achieved through regulation of G1.     

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.     

Effects of caffeine on the contractility and membrane potentials of rat atrium

Zusammenfassung Der Einfluss von Coffein auf Kontraktion und Membranpotential des Atriums der Ratte ergibt: Verkürzung der Dauer des Aktionspotentials und Beschleunigung der Geschwindigkeit von Repolarisation und Depolarisation. Ein möglicher Zusammenhang dieser Änderungen mit der erhöhten Kontraktilität wird diskutiert.

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This work was supported by a grant from the Life Insurance Medical Fund.     

Glutamate decarboxylase and γ-Aminobutyrate transaminase in developing rat brain

Résumé Le décarboxylase de glutamate (GAD) et le transaminase -aminobutyro--cétoglutarique (GABAT) ont été étudiés dans le cerveau du rat pendant le développement postnatal. Le résultat le plus frappant de cette recherche a été de montrer que le rapport de ces deux enzymes est à peu près constant au cours du développement. Ce rapport (GABAT/GAD) est de 2,5 à 3,7.