Glucagon-like peptide 2 (GLP-2) is a 33-aa proglucagon-derived peptide produced by intestinal enteroendocrine cells. GLP-2 stimulates intestinal growth and upregulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. Moreover, GLP-2 prevents intestinal hypoplasia resulting from total parenteral nutrition. However, the mechanism underlying these actions has remained unclear. nM). GLP-2 analogs that activated GLP-2R signal transduction in vitro displayed intestinotrophic activity in vivo.These results strongly suggest that GLP-2, like glucagon and GLP-1, exerts its actions through a distinct and specific novel receptor expressed in its principal target tissue, the gastrointestinal tract.Glucagon-like peptides (GLPs) encoded by the proglucagon gene play key roles in glucose homeostasis, gastric emptying, insulin secretion, and appetite regulation (1). Glucagon and GLP-1 exert their effects through distinct G protein-coupled receptors (GPCRs). In contrast, unique receptors for GLP-2, glicentin, and oxyntomodulin have not yet been identified, despite considerable attempts at receptor isolation via classical molecular biology approaches (2). Recent studies have shown that GLP-2 is a potent intestinal growth factor that stimulates crypt cell proliferation and inhibits epithelial apoptosis (3). GLP-2 promotes epithelial proliferation in both small and large intestine; however, the mechanisms utilized by GLP-2 for promotion of intestinal growth remain unclear.To understand the mechanisms underlying GLP-2 action, we have carried out studies directed at the identification and cloning of the putative GLP-2 receptor. We now have isolated rat and human cDNAs encoding GLP-2-responsive GPCRs, which show highest similarity to receptors for glucagon and GLP-1. The GLP-2R is coupled to activation of adenylate cyclase, and the receptor is expressed selectively in rat hypothalamus and the gastrointestinal tract, known targets of GLP-2 action. These findings establish GLP-2 as a novel hormone that, like glucagon and GLP-1, exerts its actions through a distinct receptor expressed in a highly tissuerestricted manner. The GLP-2R should provide an important target for isolation of small molecules mimicking GLP-2 action and for future studies delineating specific mechanisms underlying GLP-2 action in the gut and central nervous system.
The prokaryotic mRNA ribosome binding site (RBS) usually contains part or all of a polypurine domain UAAGGAGGU known as the Shine-Dalgarno (SD) sequence found just 5' to the translation initiation codon. It is now clear that the SD sequence is important for identification of the translation initiation site on the mRNA by the ribosome, and that as a result, the spacing between the SD and the initiation codon strongly affects translational efficiency (1). It is not as clear, however, whether there is a unique optimal spacing. Complications involving the definition of the spacing as well as secondary structures have obscured matters. We thus undertook a systematic study by inserting two series of synthetic RBSs of varying spacing and SD sequence into a plasmid vector containing the chloramphenicol acetyltransferase gene. Care was taken not to introduce any secondary structure. Measurements of protein expression demonstrated an optimal aligned spacing of 5 nt for both series. Since aligned spacing corresponds naturally to the spacing between the 3'-end of the 16S rRNA and the P-site, we conclude that there is a unique optimal aligned SD-AUG spacing in the absence of other complicating issues.
The costs of metal corrosion amount to several percent of the GDP of an industrialized country. [1] In the case of aluminum, chromate-based coatings [2] provide highly effective corrosion protection, but environmental regulations are increasingly restricting their use. Anodization [3] increases the thickness of the oxide layer, but it retains its porous nature.[4] Layered materials such as anionic clays (e.g., layered double hydroxides ) [5,6] and cationic clays (e.g., montmorillonite) [7] have been widely investigated as additives in organic anticorrosion coatings or as polymer-clay nanocomposite corrosion-resistant coatings. Zeolites [8,9] have also been explored as corrosion-resistant coating materials. Hydrophobic self-assembled monolayers (SAMs) [10] of surfactant molecules on the surface have recently been proposed as corrosion inhibitors but suffer from the drawbacks that the layers have limited stability and molecule-sized defects which allow water to reach the underlying surface. These problems should be mitigated if the surfactant could be incorporated in an inorganic host matrix, a thin film of which has been previously strongly bonded to the aluminum surface.Layered double hydroxides (LDHs) are one such potential inorganic host. They can be expressed by the generalwhere the cations M 2+ and M 3+ occupy the octahedral holes in a brucite-like layer and the anion A nÀ is located in the hydrated interlayer galleries.[11] The ability to vary the composition over a wide range allows materials with a wide variety of properties to be prepared. We recently showed [12] that an NiAl-LDH-CO 3 2Àfilm can be formed directly on porous anodic alumina/ aluminum (PAO/Al) substrates; since PAO/Al is the only source of Al 3+ , the thin film grows directly on the substrate and thus exhibits good adhesion and mechanical stability. [13] Treatment with sodium laurate (n-dodecanoate) results in surface-bonded laurate films showing superhydrophobicity with water contact angles (CA) greater than 1608. Here we show that intercalation of laurate anions by ion exchange with ZnAl-LDH-NO 3 À film precursors on a PAO/Al substrate leads to a hierarchical micro/nanostructured superhydrophobic film which provides a very effective corrosion-resistant coating for the underlying aluminum.The aluminum substrate was first coated with a layer of porous anodic alumina by conventional anodization and subsequently treated with an alkaline solution of zinc nitrate in the presence of an excess of nitrate anions. In addition to the peaks of the PAO/Al substrate, the XRD pattern of the film shows two low-angle reflections at 8.874 and 4.462 (Figure 1 a), which can be assigned to the [003] and [006] reflections of an LDH phase with a basal spacing of 0.887 nm, consistent with the literature for ZnAl-LDH-NO 3 À .[14] The presence of NO 3 À in the interlayer galleries of the LDH film was confirmed by the characteristic peak at 1384 cm À1 in the FTIR spectrum. It is well known that LDHs in their usual powder form readily exchange NO 3 À ions for oth...
The mid-Pleistocene transition (MPT) is widely recognized as a shift in paleoclimatic periodicity from 41- to 100-kyr cycles, which largely reflects integrated changes in global ice volume, sea level, and ocean temperature from the marine realm. However, much less is known about monsoon-induced terrestrial vegetation change across the MPT. Here, on the basis of a 1.7-million-year δ13C record of loess carbonates from the Chinese Loess Plateau, we document a unique MPT reflecting terrestrial vegetation changes from a dominant 23-kyr periodicity before 1.2 Ma to combined 100, 41, and 23-kyr cycles after 0.7 Ma, very different from the conventional MPT characteristics. Model simulations further reveal that the MPT transition likely reflects decreased sensitivity of monsoonal hydroclimate to insolation forcing as the Northern Hemisphere became increasingly glaciated through the MPT. Our proxy-model comparison suggests varied responses of temperature and precipitation to astronomical forcing under different ice/CO2 boundary conditions, which greatly improves our understanding of monsoon variability and dynamics from the natural past to the anthropogenic future.
Layered double hydroxides (LDHs), also known as hydrotalcite-like materials or anionic clays, are an important class of layered materials. Various studies show that LDHs have a wide range of applications in industry, e.g., catalyst precursors, ion exchangers, adsorbents for environmental contaminants, and substrates for the immobilization of biological material. [1][2][3][4] However, for the purpose of developing novel innovative applications of LDHs as materials for chemical sensors, [5,6] clay-modified electrodes, [7,8] corrosion-resistant coatings, [9,10] membrane catalysis, or components in optical and magnetic devices, intensive studies have been conducted aimed at organizing LDH microcrystals into large uniformly aligned 2D arrays or films. Several methods have been employed to fabricate LDH films on different substrates thus far. For example, LDH microcrystals have been deposited on indium-doped SnO 2 coated glass, platinum disks, and gold electrode surfaces from colloidal suspensions in order to prepare LDH films for electrode modification by deposition [11,12] and Langmuir-Blodgett methods. [8] Most of the films obtained, however, were not oriented or uniformly aligned as it is hard to control the LDH crystallite orientation using these methods. Recently, new techniques have been reported for the fabrication of oriented LDH films. Pinnavaia and co-workers found that colloidal suspensions of LDHs obtained through hydrolysis of LDH/methoxide were able to form transparent and smooth films, [13] in which the LDH microcrystals were extremely well oriented. By employing ultrasonification, Jung and co-workers obtained a monolayer of LDH films with a high packing density and a preferred orientation with the c-axis perpendicular to the substrate surface (ab-face parallel). [14,15] However, this route did not allow control of the orientation of the LDH microcrystals with respect to the substrate plane because of the intrinsic propensity of the microcrystals to align in an orientation that leads to maximum faceto-face contact between the crystals and the substrate. In spite of the progress made during the last decade in research on LDH films and their crystal orientation, there has been no synthetic method for directly growing uniformly aligned LDH polycrystalline films from a substrate. Growing thin films directly from a substrate considerably improves the adherence and the mechanical stability of the resulting thin film, compared to colloidal-deposition techniques (for example, spin-coating, dip-coating, and screen-printing).[16] Therefore, the exploration of new approaches to fabricate oriented LDH films on substrates is of significant importance. Among the existing synthetic methods to fabricate inorganic films, hydrothermal synthesis shows high flexibility in terms of control of the structure and morphology of the resulting inorganic materials. It is also a well-known pathway for fabricating inorganic films with the desired micro-or nanostructure and controlled crystal orientation. Our group has recently repor...
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