Family-B G-protein-coupled receptors

All G-protein-coupled receptors (GPCRs) share a common molecular architecture (with seven putative transmembrane segments) and a common signaling mechanism, in that they interact with G proteins (heterotrimeric GTPases) to regulate the synthesis of intracellular second messengers such as cyclic AMP, inositol phosphates, diacylglycerol and calcium ions. Historically, GPCRs have been classified into six families, which were thought to be unrelated; three of these are found in vertebrates. Recent work has identified several new GCPR families and suggested the possibility of a common evolutionary origin for all of them. Family B (the secretin-receptor family or 'family 2') of the GPCRs is a small but structurally and functionally diverse group of proteins that includes receptors for polypeptide hormones, molecules thought to mediate intercellular interactions at the plasma membrane and a group of Drosophila proteins that regulate stress responses and longevity. Family-B GPCRs have been found in all animal species investigated, including mammals, Caenorhabditis elegans and Drosophila melanogaster, but not in plants, fungi or prokaryotes. In this article, I describe the structures and functions of family-B GPCRs and propose a simplified nomenclature for these proteins

PERAN PERBANKAN SYARIAH DALAM UMKM UNTUK MENGEMBANGKAN EKONOMI INDONESIA

This research is descriptive qualitative using literature study obtained from several sources of secondary data, in the form of theories, reports, research results and others.It aims to analyze the role of Islamic banking in UMKM to  Indonesia's economic growth. Crisis conditions occurred during the period 1997 to 1998, only the UMKM (Micro, Small and Medium Enterprises) sector was able to remain strong after the economic crisis. The number of UMKM did not decrease, instead their growth increased . The efforts of Islamic banking in developing the country's economy include providing financing through micro, small and medium enterprises. As the government pays attention to the development of UMKM in Indonesia, sharia banking also participates in empowering these UMKM  which will then stimulate economic sectors and spur economic growth

The Fates of Mutant Lineages and the Distribution of Fitness Effects of Beneficial Mutations in Laboratory Budding Yeast Populations

The outcomes of evolution are determined by which mutations occur and fix. In rapidly adapting microbial populations, this process is particularly hard to predict because lineages with different beneficial mutations often spread simultaneously and interfere with one another’s fixation. Hence to predict the fate of any individual variant, we must know the rate at which new mutations create competing lineages of higher fitness. Here, we directly measured the effect of this interference on the fates of specific adaptive variants in laboratory Saccharomyces cerevisiae populations and used these measurements to infer the distribution of fitness effects of new beneficial mutations. To do so, we seeded marked lineages with different fitness advantages into replicate populations and tracked their subsequent frequencies for hundreds of generations. Our results illustrate the transition between strongly advantageous lineages that decisively sweep to fixation and more moderately advantageous lineages that are often outcompeted by new mutations arising during the course of the experiment. We developed an approximate likelihood framework to compare our data to simulations and found that the effects of these competing beneficial mutations were best approximated by an exponential distribution, rather than one with a single effect size. We then used this inferred distribution of fitness effects to predict the rate of adaptation in a set of independent control populations. Finally, we discuss how our experimental design can serve as a screen for rare, large-effect beneficial mutations.Organismic and Evolutionary BiologyPhysic

IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

Morphological and process dynamics of the Lower Mississippi River

This thesis uses data sets at a range of spatial and temporal scales to examine the geomorphological response of the Lower Mississippi River to engineering and management. During the twentieth century the geomorphology of the Lower Mississippi River has been transformed by a series of engineering modifications to improve flood control and aid navigation. These have included steepening of the longitudinal profile by removal of the most sinuous bends, fixing the river to a constant planform through extensive bank stabilisation, and regulating sediment movement through the channel system by dike field construction. Prior to these modifications, the Lower Mississippi River adjusted its planform morphology to satisfy large-scale flow resistance requirements. However, this mode of adjustment has been effectively removed and adjustments are now restricted to the long profile and cross-sectional form. Morphological analysis reveals that the river has responded to engineering intervention at two principal scales: by vertical changes in the elevation of the channel bed at the reach-scale; and by increasing large-scale bedform resistance at the sub-reach scale through longitudinal and cross-sectional adjustments. These mutual changes are consistent with the changes in water surface elevation in the post-modification period noted by Biedenharn and Watson (1997). However, analysis of morphological and process dynamics at shorter timescales shows that geomorphological response remains difficult to explain. This is because geomorphological behaviour at any scale, and in any location within an alluvial channel, is a product of complex spatially-distributed feedbacks between operating processes and multiple scales of channel morphology. This has general significance in terms of research design because detecting the complexity at each scale of adjustment, and forming linkages between scales of adjustment, is dependent on taking into account all possible degrees of freedom, and applying a range of complementary analytical techniques

Morphological and process dynamics of the Lower Mississippi River

This thesis uses data sets at a range of spatial and temporal scales to examine the geomorphological response of the Lower Mississippi River to engineering and management. During the twentieth century the geomorphology of the Lower Mississippi River has been transformed by a series of engineering modifications to improve flood control and aid navigation. These have included steepening of the longitudinal profile by removal of the most sinuous bends, fixing the river to a constant planform through extensive bank stabilisation, and regulating sediment movement through the channel system by dike field construction. Prior to these modifications, the Lower Mississippi River adjusted its planform morphology to satisfy large-scale flow resistance requirements. However, this mode of adjustment has been effectively removed and adjustments are now restricted to the long profile and cross-sectional form. Morphological analysis reveals that the river has responded to engineering intervention at two principal scales: by vertical changes in the elevation of the channel bed at the reach-scale; and by increasing large-scale bedform resistance at the sub-reach scale through longitudinal and cross-sectional adjustments. These mutual changes are consistent with the changes in water surface elevation in the post-modification period noted by Biedenharn and Watson (1997). However, analysis of morphological and process dynamics at shorter timescales shows that geomorphological response remains difficult to explain. This is because geomorphological behaviour at any scale, and in any location within an alluvial channel, is a product of complex spatially-distributed feedbacks between operating processes and multiple scales of channel morphology. This has general significance in terms of research design because detecting the complexity at each scale of adjustment, and forming linkages between scales of adjustment, is dependent on taking into account all possible degrees of freedom, and applying a range of complementary analytical techniques

Peptidergic receptors

The term neuropeptides refers to a relatively large number of biologically active molecules localized to discrete cell populations of nervous system, including autonomic ganglion neurons and their effector cells. Different combinations of transmitters and peptides are found in ganglionic cells of the autonomic system which comprise a functional “chemical code” for neurons subserving specific actions. Generally, peptidergic receptors are G-protein coupled receptors acting through multiple transduction pathways which reflect the pleiotropic actions of peptides. This section represents a current view of the most important actions of peptides and their receptors in the autonomic nervous system and in peripheral organs.L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com

IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data

The IUPHAR database is an established online reference resource for several important classes of human drug targets and related proteins. As well as providing recommended nomenclature, the database integrates information on the chemical, genetic, functional and pathophysiological properties of receptors and ion channels, curated and peer-reviewed from the biomedical literature by a network of experts. The database now includes information on 616 gene products from four superfamilies in human and rodent model organisms: G protein-coupled receptors, voltage- and ligand-gated ion channels and, in a recent update, 49 nuclear hormone receptors (NHRs). New data types for NHRs include details on co-regulators, DNA binding motifs, target genes and 3D structures. Other recent developments include curation of the chemical structures of approximately 2000 ligand molecules, providing electronic descriptors, identifiers, link-outs and calculated molecular properties, all available via enhanced ligand pages. The interface now provides intelligent tools for the visualization and exploration of ligand structure-activity relationships and the structural diversity of compounds active at each target. The database is freely available at http://www.iuphar-db.org

Terrace reconstruction and long profile projection: a case study from the Solent river system near Southampton, England

River terrace sequences are important frameworks for archaeological evidence and as such it is important to produce robust correlations between what are often fragmentary remnants of ancient terraces. This paper examines both conceptual and practical issues related to such correlations, using a case study from the eastern part of the former Solent River system near Southampton, England. In this region two recent terrace schemes have been constructed using different data to describe the terrace deposits: one based mainly on terrace surfaces; the other on gravel thicknesses, often not recording the terrace surface itself. The utility of each of these types of data in terrace correlation is discussed in relation to the complexity of the record, the probability of post-depositional alteration of surface sediments and comparison of straight-line projections with modern river long profiles. Correlation using age estimates is also discussed, in relation to optically-stimulated luminescence dating of sand lenses within terrace gravels in this region during the PASHCC project. It is concluded that the need for replication at single sites means that this approach has limited use for correlative purposes, although dating of sediments is important for understanding wider landscape evolution and patterns of human occupation