Localisation and detection of a polymorphism in the human skeletal Beta-Tropomyosin gene (TPM2)

Tropomyosin is one of the components of the thin filaments of muscle, binding to actin, and, together with troponin, regulating contraction in a calcium-dependent manner (Cho et al.,1990). There are at least four distinct tropomyosin genes in vertebrates and each may encode at least six different isoforms of tropomyosin by alternate splicing (Novy et al, 1993; MacLeod et al., 1988). The alpha-tropomyosin gene TPM1 has recently been localised to 15q22 (Eyre et al, 1994) and has been shown to be mutated in some cases of familial hypertrophic cardiomyopathy (Thierfelder et al., 1994). The alpha-tropomyosin gene TPM3 has been recently localised to 1q22-q23 (Wilton et al, 1994) and has been shown to be mutated in a family with autosomal dominant nemaline myopathy (Laing, 1994, unpublished observations). Each muscle-specific gene is possibly associated with an inherited muscle disease, if there is a disease causing mutation in the gene. Precise mapping of muscle genes therefore becomes important in relation to mapping muscle diseases (Eyre et al., 1993). A sequence tagged site (STS) (Olson et al., 1989) was developed for the human beta tropomyosin gene (TPM2). The STS was used to amplify DNA from somatic cell hybrids to localise TPM2 to human chromosome 9. Genomic clones isolated with the STS product were in tum used in fluorescent in situ hybridisation (Callen et al., 1992) to metaphase chromosome spreads to further localise TPM2 to 9pl3.1 (Hunt et al., 1995). This project should assist those laboratories searching for candidate genes of inherited muscular diseases that are linked within the region of the TPM2 gene and may assist in the precise diagnosis of people with these diseases (Akkari, 1994). Localising TPM2 also lays a foundation for a better understanding of the role of tropornyosins in muscle and nonmuscle cells. A polymorphism was also discovered in the 3\u27UTR of TPM2, using single stranded conformation analysis (SSCA). The primers used were 5\u27-AAGTCTATGCCAGAAGATG-3\u27 and the complementary strand 5\u27-CCGTGACCGAAGTAGGAAAT-3\u27 creating a 259 bp sequence tagged site (STS). Sequencing of the STS revealed that there were two variations of the 11th base in the 3\u27UTR: a guanine and an adenine. Genomic DNA from 97 unrelated individuals was screened by SSCA and the allelic frequency was determined to be for the common allele (guanine) 0.91 and the rare allele (adenine) 0.09. The heterozygosity was 0.16. There is a Bgl I restriction site at the common allele polymorphic location. A Bgl I restriction digest of the 259 bp STS produces two fragments (88 & 171 bp) for homozygous individuals with the common allele, three fragments (88, 171 and 259 bp) for heterozygous individuals and a single fragment (259 bp) for homozygous individual with the rare allele. The discovery of this polymorphism will be entered on the CEPH map and is useful for researchers as a linkage and physical marker in the human genome project, especially since the TPM2 gene has now been localised to 9p13.1

Adsorption of the prototypical organic corrosion inhibitor benzotriazole on the Cu(100) surface

The interaction of benzotriazole (BTAH) with Cu(100) has been studied as a function of BTAH exposure in a joint experimental and theoretical effort. Scanning tunnelling microscopy (STM), X-ray photoelectron spectroscopy (XPS), high resolution electron energy loss spectroscopy (HREELS) and density functional theory (DFT) calculations have been combined to elucidate the structural and chemical characteristics of this system. BTAH is found to deprotonate upon adsorption on the copper surface and to adopt an orientation that depends on the molecular coverage. Benzotriazolate (BTA) species initially lie with their planes parallel to the substrate but, at a higher molecular coverage, a transition occurs to an upright adsorption geometry. Upon increasing the BTAH exposure, different phases of vertically aligned BTAs are observed with increasing molecular densities until a final, self-limiting monolayer is developed. Both theory and experiment agree in identifying CuBTA and Cu(BTA)2 metal-organic complexes as the fundamental building blocks of this monolayer. This work shows several similarities with the results of previous studies on the interaction of benzotriazole with other low Miller index copper surfaces, thereby ideally completing and concluding them. The overall emerging picture constitutes an important starting point for understanding the mechanism for protection of copper from corrosion

Conformations of Linear DNA

We examine the conformations of a model for under- and overwound DNA. The molecule is represented as a cylindrically symmetric elastic string subjected to a stretching force and to constraints corresponding to a specification of the link number. We derive a fundamental relation between the Euler angles that describe the curve and the topological linking number. Analytical expressions for the spatial configurations of the molecule in the infinite- length limit were obtained. A unique configuraion minimizes the energy for a given set of physical conditions. An elastic model incorporating thermal fluctuations provides excellent agreement with experimental results on the plectonemic transition.Comment: 5 pages, RevTeX; 6 postscript figure

Morphologies of AGN host galaxies using HST/ACS in the CDFS-GOODS field

Using HST/ACS images in four bands F435W, F606W, F775W and F850LP, we identify optical counterparts to the X-ray sources in the Chandra Deep Field South in the GOODS South field. A detailed study has been made of these sources to study their morphological types. We use methods like decomposition of galaxy luminosity profiles, color maps and visual inspection of 192 galaxies which are identified as possible optical counterparts of Chandra X-ray sources in the CDFS-GOODS field. We find that most moderate luminosity AGN hosts are bulge dominated in the redshift range (z \approx 0.4-1.3), but not merging/interacting galaxies. This implies probable fueling of the moderate luminosity AGN by mechanisms other than those merger driven.Comment: pdflatex, accepted in ApSS. revisions in tex

Adult beginner distance language learner perceptions and use of assignment feedback

This qualitative study examines perceptions and use of assignment feedback among adult beginner modern foreign language learners on higher education distance learning courses. A survey of responses to feedback on assignments by 43 Open University students on beginner language courses in Spanish, French, and German indicated that respondents can be classified into three groups: those who use feedback strategically by integrating it into the learning process and comparing it with, for example, informal feedback from interaction with native speakers, those who take note of feedback, but seem not to use it strategically, and those who appear to take little account of either marks or feedback. The first group proved to be the most confident and most likely to maintain their motivation in the longer term. The conclusion discusses some of the pedagogical and policy implications of the findings

Lesbian and bisexual women's human rights, sexual rights and sexual citizenship: negotiating sexual health in England.

Lesbian and bisexual women's sexual health is neglected in much Government policy and practice in England and Wales. This paper examines lesbian and bisexual women's negotiation of sexual health, drawing on findings from a small research project. Themes explored include invisibility and lack of information, influences on decision-making and sexual activities and experiences of services and barriers to sexual healthcare. Key issues of importance in this respect are homophobic and heterosexist social contexts. Drawing on understandings of lesbian, gay and bisexual human rights, sexual rights and sexual citizenship, it is argued that these are useful lenses through which to examine and address lesbian and bisexual women's sexual health and related inequalities

Phase Separation in a ternary DPPC DOPC POPC System with Reducing Hydration

The maintenance of plasma membrane structure is vital for the viability of cells. Disruption of this structure can lead to cell death. One important example is the macroscopic phase separation observed during dehydration associated with desiccation and freezing, often leading to loss of permeability and cell death. It has previously been shown that the hybrid lipid 1 palmitoyl 2 oleoyl sn glycero 3 phosphocholine POPC can act as a line active component in ternary lipid systems, inhibiting macroscopic phase separation and stabilising membrane microdomains in lipid vesicles [1]. The domain size is found to decrease with increasing POPC concentration until complete mixing is observed. However, no such studies have been carried out at reduced hydration. To examine if this phase separation is unique to vesicles in excess water, we have conducted studies on several binary and ternary model membrane systems at both reduced hydration powder type samples and oriented membrane stacks and in excess water supported lipid bilayers at 0.2 mol fraction POPC, in the range where microdomain stabilisation is reported. Differential scanning calorimetry DSC and Fourier transform infrared spectroscopy FTIR are used to map phase transition temperatures, with X ray and neutron scattering providing details of the changes in lipid packing and phase information within these boundaries. Atomic force microscopy AFM is used to image bilayers on a substrate in excess water. In all cases, macroscopic phase separation was observed rather than microdomain formation at this molar ratio. Thus POPC does not stabilise microdomains under these conditions, regardless of the type of model membrane, hydration or temperature. Thus we conclude that the driving force for separation under these conditions overcomes any linactant effects of the hybrid lipi

The Effect of Convection on Disorder in Primary Cellular and Dendritic Arrays

Directional solidification studies have been carried out to characterize the spatial disorder in the arrays of cells and dendrites. Different factors that cause array disorder are investigated experimentally and analyzed numerically. In addition to the disorder resulting from the fundamental selection of a range of primary spacings under given experimental conditions, a significant variation in primary spacings is shown to occur in bulk samples due to convection effects, especially at low growth velocities. The effect of convection on array disorder is examined through directional solidification studies in two different alloy systems, Pb-Sn and Al-Cu. A detailed analysis of the spacing distribution is carried out, which shows that the disorder in the spacing distribution is greater in the Al-Cu system than in Pb-Sn system. Numerical models are developed which show that fluid motion can occur in both these systems due to the negative axial density gradient or due the radial temperature gradient which is always present in Bridgman growth. The modes of convection have been found to be significantly different in these systems, due to the solute being heavier than the solvent in the Al-Cu system and lighter than it in the Pb-Sn system. The results of the model have been shown to explain experimental observations of higher disorder and greater solute segregation in a weakly convective Al-Cu system than those in a highly convective Pb-Sn system

Mesophyll porosity is modulated by the presence of functional stomata

The formation of stomata and leaf mesophyll airspace must be coordinated to establish an efficient and robust network that facilitates gas exchange for photosynthesis, however the mechanism by which this coordinated development occurs remains unclear. Here, we combine microCT and gas exchange analyses with measures of stomatal size and patterning in a range of wild, domesticated and transgenic lines of wheat and Arabidopsis to show that mesophyll airspace formation is linked to stomatal function in both monocots and eudicots. Our results support the hypothesis that gas flux via stomatal pores influences the degree and spatial patterning of mesophyll airspace formation, and indicate that this relationship has been selected for during the evolution of modern wheat. We propose that the coordination of stomata and mesophyll airspace pattern underpins water use efficiency in crops, providing a target for future improvement

Separating Regular Languages by Piecewise Testable and Unambiguous Languages

Abstract. Separation is a classical problem asking whether, given two sets belonging to some class, it is possible to separate them by a set from another class. We discuss the separation problem for regular languages. We give a Ptime algorithm to check whether two given regular languages are separable by a piecewise testable language, that is, whether a BΣ1(<) sentence can witness that the languages are disjoint. The proof refines an algebraic argument from Almeida and the third author. When separation is possible, we also express a separator by saturating one of the original languages by a suitable congruence. Following the same line, we show that one can as well decide whether two regular languages can be separated by an unambiguous language, albeit with a higher complexity.