Store Environment: Its Importance and Consumers' Expectations on Ca-sual - wear Chain Stores in Honk Kong

This study attempted to examine the importance of storeenvironment in affecting consumers'store choice deci-sion;the relative importance among the three environ-mental factors;and consumers'expectations on store en-vironment for the casual-wear chain stores in HongKong.Julie Baker's Three-category framework onstore environments namely ambient,design and socialfactors was adopted for investigation.The results indi-cated that the store environment was important in affect-ing consumers'selection of store for shopping.It alsorevealed that social factor was perceived relatively im-portant than ambient and design factors.Nine store ex-pectation dimensions were categorised and the resultdemonstrated that most respondents were concerned onthe social aspect in their expectation of having a satisfy-ing store environment.     

The inner jet of an active galactic nucleus as revealed by a radio-to-gamma-ray outburst

Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV gamma-ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images.     

Detection of single base substitutions in total genomic DNA

Certain single base substitutions causing genetic diseases or resulting in polymorphisms linked to mutant alleles, alter a restriction enzyme cleavage site and can therefore be detected in total genomic DNA using DNA blots. Many base substitutions do not lead to an altered restriction site, but these can be detected using synthetic oligonucleotides as hybridization probes if the DNA sequence surrounding the base substitution is known. In the case of beta-thalassaemia, where 22 different single base mutations have been identified, a large number of probes would be required for diagnosis. An approach which was used to detect mutations in viral DNA involves the S1 nuclease treatment of heteroduplexes formed between wild-type and mutant DNA. Although certain single base mismatches are cleaved by S1 nuclease (ref. 11 and T. Shenk, personal communication), many other mismatches examined by this procedure are not cleaved (B. Seed, personal communication; R.M.M., unpublished data). Heteroduplexes between mutant and wild-type subgenomic fragments of double-stranded reovirus RNA migrate slower than the corresponding homoduplexes in polyacrylamide gels containing 7 M urea, but it is not known whether this method is applicable to DNA heteroduplexes containing single base mismatches. Here we describe a procedure that involves the electrophoretic separation of DNA heteroduplexes in a well-characterized gel system. We show that four different human beta-thalassaemia alleles with known single base mutations can be detected with as little as 5 micrograms of total genomic DNA. The method should be useful in the localization and diagnosis of mutations associated with genetic diseases.     

Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A breast cancer cells: consequences on calcium signalling,cell migration and proliferation

Store-operated Ca²⁺ entry is a pathway that is remodelled in a variety of cancers, and altered expression of the components of store-operated Ca²⁺ entry is a feature of breast cancer cells of the basal molecular subtype. Studies of store-operated Ca²⁺ entry in breast cancer cells have used non-specific pharmacological inhibitors, complete depletion of intracellular Ca²⁺ stores and have mostly focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies compared the effects of the selective store-operated Ca²⁺ entry inhibitors Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca²⁺ ([Ca²⁺]_CYT) changes induced by physiological stimuli in a different breast cancer basal cell line model, MDA-MB-468. The effects of these agents on proliferation as well as serum and epidermal growth factor (EGF) induced migration were also assessed. Activation with the purinergic receptor activator adenosine triphosphate, produced a sustained increase in [Ca²⁺]_CYT that was entirely dependent on store-operated Ca²⁺ entry. The protease activated receptor 2 activator, trypsin, and EGF also produced Ca²⁺ influx that was sensitive to both Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells was sensitive to both store-operated Ca²⁺ inhibitors. However, proliferation and EGF-activated migration was differentially affected by Synta66 and YM58483. These studies highlight the need to define the exact mechanisms of action of different store-operated calcium entry inhibitors and the impact of such differences in the control of tumour progression pathways.     

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5'-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis.     

An abundant, truncated human sulfonylurea receptor 1 splice variant has prodiabetic properties and impairs sulfonylurea action

An alternatively spliced form of human sulfonylurea receptor (SUR) 1 mRNA lacking exon 2 (SUR1Δ2) has been identified. The omission of exon 2 caused a frame shift and an immediate stop codon in exon 3 leading to translation of a 5.6-kDa peptide that comprises the N-terminal extracellular domain and the first transmembrane helix of SUR1. Based on a weak first splice acceptor site in the human SUR1 gene (ABCC8), RT-PCR revealed a concurrent expression of SUR1Δ2 and SUR1. The SUR1Δ2/(SUR1 + SUR1Δ2) mRNA ratio differed between tissues, and was lowest in pancreas (46%), highest in heart (88%) and negatively correlated with alternative splice factor/splicing factor 2 (ASF/SF2) expression. In COS-7 cells triple transfected with SUR1Δ2/SUR1/Kir6.2, the SUR1Δ2 peptide co-immunoprecipitated with Kir6.2, thereby displacing two of four SUR1 subunits on the cell surface. The ATP sensitivity of these hybrid ATP-sensitive potassium channels (K_ATP) channels was reduced by about sixfold, as shown with single-channel recordings. RINm5f rat insulinoma cells, which genuinely express SUR1 but not SUR1Δ2, exhibited a strongly increased K_ATP channel current upon transfection with SUR1Δ2. This led to inhibition of glucose-induced depolarization, calcium flux, insulin release and glibenclamide action. A non-mutagenic SNP on nucleotide position 333 (Pro69Pro) added another exonic splicing enhancer sequence detected by ASF/SF2, reduced relative abundance of SUR1Δ2 and slightly protected from non-insulin dependent diabetes in homozygotic individuals. Thus, SUR1Δ2 represents an endogenous K_ATP-channel modulator with prodiabetic properties in islet cells. Its predominance in heart may explain why high-affinity sulfonylurea receptors are not found in human cardiac tissue.     

A 'dry' condensation origin for circumstellar carbonates

The signature of carbonate minerals has long been suspected in the mid-infrared spectra of various astrophysical environments such as protostars. Abiogenic carbonates are considered as indicators of aqueous mineral alteration in the presence of CO2-rich liquid water. The recent claimed detection of calcite associated with amorphous silicates in two planetary nebulae and protostars devoid of planetary bodies questions the relevance of this indicator; but in the absence of an alternative mode of formation under circumstellar conditions, this detection remains controversial. The main dust component observed in circumstellar envelopes is amorphous silicates, which are thought to have formed by non-equilibrium condensation. Here we report experiments demonstrating that carbonates can be formed with amorphous silicates during the non-equilibrium condensation of a silicate gas in a H2O-CO2-rich vapour. We propose that the observed astrophysical carbonates have condensed in H2O(g)-CO2(g)-rich, high-temperature and high-density regions such as evolved stellar winds, or those induced by grain sputtering upon shocks in protostellar outflows.     

Crystal structure and mechanism of a calcium-gated potassium channel

Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K(+) channel that opens in response to intracellular Ca(2+). We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K(+) channel (MthK) from Methanobacterium thermoautotrophicum in the Ca(2+)-bound, opened state. Eight RCK domains (regulators of K(+) conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca(2+) binding in a simple manner to perform mechanical work to open the pore.