Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy

Background  

Ca²⁺ is known to be involved in a number of metastatic processes including motility and proliferation which can result in store-depletion of Ca²⁺. Up regulation of genes which contribute to store operated channel (SOC) activity may plausibly be necessary for these processes to take place efficiently. TRPC proteins constitute a family of conserved Ca²⁺-permeable channels that have been shown to contribute to SOC activity.     

Arsenic transport by zebrafish aquaglyceroporins

Background  

Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (As^III) is one of the major species that exists environmentally. The transport of As^III has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct As^III and its organic metabolite, monomethylarsenite (MAs^III). However, the transport of As^III and MAs^III in in any fish species has not been characterized.     

The orthologue of the "acatalytic" mammalian ART4 in chicken is an arginine-specific mono-ADP-ribosyltransferase

Background  

Human ART4, carrier of the GPI-(glycosyl-phosphatidylinositol) anchored Dombrock blood group antigens, is an apparently inactive member of the mammalian mono-ADP-ribosyltransferase (ART) family named after the enzymatic transfer of a single ADP-ribose moiety from NAD⁺ to arginine residues of extracellular target proteins. All known mammalian ART4 orthologues are predicted to lack ART activity because of one or more changes in essential active site residues that make up the R-S-EXE motif. So far, no other function has been detected.     

The role of iron uptake in pathogenicity and symbiosis in <Emphasis Type="Italic">Photorhabdus luminescens</Emphasis> TT01

Background  

Photorhabdus are Gram negative bacteria that are pathogenic to insect larvae whilst also having a mutualistic interaction with nematodes from the family Heterorhabditis. Iron is an essential nutrient and bacteria have different mechanisms for obtaining both the ferrous (Fe²⁺) and ferric (Fe³⁺) forms of this metal from their environments. In this study we were interested in analyzing the role of Fe³⁺ and Fe²⁺ iron uptake systems in the ability of Photorhabdus to interact with its invertebrate hosts.     

A 4-trifluoromethyl analogue of celecoxib inhibits arthritis by suppressing innate immune cell activation

Introduction  

Celecoxib, a highly specific cyclooxygenase-2 (COX-2) inhibitor has been reported to have COX-2-independent immunomodulatory effects. However, celecoxib itself has only mild suppressive effects on arthritis. Recently, we reported that a 4-trifluoromethyl analogue of celecoxib (TFM-C) with 205-fold lower COX-2-inhibitory activity inhibits secretion of IL-12 family cytokines through a COX-2-independent mechanism that involves Ca²⁺-mediated intracellular retention of the IL-12 polypeptide chains. In this study, we explored the capacity of TFM-C as a new therapeutic agent for arthritis.     

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices

Background  

The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K⁺, Ca²⁺ and Na²⁺ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field.     

Molecular evolution and functional divergence of the bestrophin protein family

Background  

Mutations in human bestrophin 1 are associated with at least three autosomal-dominant macular dystrophies including Best disease, adult onset vitelliform macular dystrophy and autosomal dominant vitreo-retinochoroidopathy. The protein is integral to the membrane and is likely involved in Ca²⁺-dependent transport of chloride ions across cellular membranes. Bestrophin 1 together with its three homologues forms a phylogenetically highly conserved family of proteins.     

Evolution and functional divergence of the anoctamin family of membrane proteins

Background  

The anoctamin family of transmembrane proteins are found in all eukaryotes and consists of 10 members in vertebrates. Ano1 and ano2 were observed to have Ca²⁺ activated Cl^- channel activity. Recent findings however have revealed that ano6, and ano7 can also produce chloride currents, although with different properties. In contrast, ano9 and ano10 suppress baseline Cl^- conductance when co-expressed with ano1 thus suggesting that different anoctamins can interfere with each other. In order to elucidate intrinsic functional diversity, and underlying evolutionary mechanism among anoctamins, we performed comprehensive bioinformatics analysis of anoctamin gene family.     

A family of putative Kir potassium channels in prokaryotes

Background  

Prior to this report, members of the inward rectifier family, or Kir, have been found only in eukaryotes. Like most K⁺ channels, the pore-forming part of the protein is formed by four identical, or closely related, subunits. Each subunit contains a transmembrane M1-P-M2 motif that is followed by a relatively large C-terminus region unique to Kir's.     

Domain swapping reveals that the N-terminal domain of the sensor kinase KdpD in Escherichia coli is important for signaling

Background  

The KdpD/KdpE two-component system of Escherichia coli regulates expression of the kdpFABC operon encoding the high affinity K⁺ transport system KdpFABC. The input domain of KdpD comprises a domain that belongs to the family of universal stress proteins (Usp). It has been previously demonstrated that UspC binds to this domain, resulting in KdpD/KdpE scaffolding under salt stress. However the mechanistic significance of this domain for signaling remains unclear. Here, we employed a "domain swapping" approach to replace the KdpD-Usp domain with four homologous domains or with the six soluble Usp proteins of E. coli.     

Energy-saving policies and low-energy residential buildings: an LCA case study to support decision makers in Piedmont (Italy)

Background, aim and scope  

A low-energy family house recently built in Northern Italy was selected by Regione Piemonte as an outstanding example of resource efficient building. An economic incentive was awarded to cover the extra costs of the thermal insulation, windows and equipment in order to decrease the yearly winter heat requirement from the legal standard of 109 to 10 kW h/m², while existing buildings in the study area typically require 200 kW h/m². As the building was claimed to be sustainable on the basis of its outstanding energy-saving performance, an ex post life cycle assessment (LCA) was set up to understand whether, and to what extent, the positive judgement could be confirmed in a life cycle perspective.     

Genomic survey,characterization and expression profile analysis of the peptide transporter family in rice (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.)

Background  

Peptide transporter (PTR) family whose member can transport di-/tripeptides and nitrate is important for plant growth and development. Although the rice (Oryza sativa L.) genome has been sequenced for a few years, a genomic survey, characterization and expression profile analysis of the PTR family in this species has not been reported.     

High affinity binding of proteins HMG1 and HMG2 to semicatenated DNA loops

Background  

Proteins HMG1 and HMG2 are two of the most abundant non histone proteins in the nucleus of mammalian cells, and contain a domain of homology with many proteins implicated in the control of development, such as the sex-determination factor Sry and the Sox family of proteins. In vitro studies of interactions of HMG1/2 with DNA have shown that these proteins can bind to many unusual DNA structures, in particular to four-way junctions, with binding affinities of 10⁷ to 10⁹ M^-1.     

Expansion and evolution of insect GMC oxidoreductases

Background  

The GMC oxidoreductases comprise a large family of diverse FAD enzymes that share a homologous backbone. The relationship and origin of the GMC oxidoreductase genes, however, was unknown. Recent sequencing of entire genomes has allowed for the evolutionary analysis of the GMC oxidoreductase family.     

RNA:(guanine-N2) methyltransferases RsmC/RsmD and their homologs revisited – bioinformatic analysis and prediction of the active site based on the uncharacterized Mj0882 protein structure

Background  

Escherichia coli guanine-N2 (m²G) methyltransferases (MTases) RsmC and RsmD modify nucleosides G1207 and G966 of 16S rRNA. They possess a common MTase domain in the C-terminus and a variable region in the N-terminus. Their C-terminal domain is related to the YbiN family of hypothetical MTases, but nothing is known about the structure or function of the N-terminal domain.     

Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2<Superscript>ΔGF122</Superscript>) and structural roles of F122 in target recognition

Background  

ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca²⁺-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca²⁺ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2^ΔGF122, lacks Gly¹²¹Phe¹²² and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated.     

Multigene family isoform profiling from blood cell lineages

Background  

Analysis of cell-selective gene expression for families of proteins of therapeutic interest is crucial when deducing the influence of genes upon complex traits and disease susceptibility. Presently, there is no convenient tool for examining isoform-selective expression for large gene families. A multigene isoform profiling strategy was developed and used to investigate the inwardly rectifying K⁺ (Kir) channel family in human leukocytes. Comprised of seven subfamilies, Kir channels have important roles in setting the resting membrane potential in excitable and non-excitable cells.     

Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression

Background  

S100 proteins, a multigenic family of non-ubiquitous cytoplasmic Ca²⁺-binding proteins, have been linked to human pathologies in recent years. Dysregulated expression of S100 proteins, including S100A9, has been reported in the epidermis as a response to stress and in association with neoplastic disorders. Recently, we characterized a regulatory element within the S100A9 promotor, referred to as MRE that drives the S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner (Kerkhoff et al. (2002) J. Biol. Chem. 277, 41879–41887).     

Molecular and functional analyses of COPT/Ctr-type copper transporter-like gene family in rice

Background  

The copper (Cu) transporter (COPT/Ctr) gene family has an important role in the maintenance of Cu homeostasis in different species. The rice COPT-type gene family consists of seven members (COPT1 to COPT7). However, only two, COPT1 and COPT5, have been characterized for their functions in Cu transport.