G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity.

The alpha 1B-adrenergic receptor (alpha 1B-ADR) is a member of the G-protein-coupled family of transmembrane receptors. When transfected into Rat-1 and NIH 3T3 fibroblasts, this receptor induces focus formation in an agonist-dependent manner. Focus-derived, transformed fibroblasts exhibit high levels of functional alpha 1B-ADR expression, demonstrate a catecholamine-induced enhancement in the rate of cellular proliferation, and are tumorigenic when injected into nude mice. Induction of neoplastic transformation by the alpha 1B-ADR, therefore, identifies this normal cellular gene as a protooncogene. Mutational alteration of this receptor can lead to activation of this protooncogene, resulting in an enhanced ability of agonist to induce focus formation with a decreased latency and quantitative increase in transformed foci. In contrast to cells expressing the wild-type alpha 1B-ADR, focus formation in "oncomutant"-expressing cell lines appears constitutively activated with the generation of foci in unstimulated cells. Further, these cell lines exhibit near-maximal rates of proliferation even in the absence of catecholamine supplementation. They also demonstrate an enhanced ability for tumor generation in nude mice with a decreased period of latency compared with cells expressing the wild-type receptor. Thus, the alpha 1B-ADR gene can, when overexpressed and activated, function as an oncogene inducing neoplastic transformation. Mutational alteration of this receptor gene can result in the activation of this protooncogene, enhancing its oncogenic potential. These findings suggest that analogous spontaneously occurring mutations in this class of receptor proteins could play a key role in the induction or progression of neoplastic transformation and atherosclerosis.

Heat-labile enterotoxin: beyond G(m1) binding.

Enterotoxigenic Escherichia coli (ETEC) is a significant source of morbidity and mortality worldwide. One major virulence factor released by ETEC is the heat-labile enterotoxin LT, which is structurally and functionally similar to cholera toxin. LT consists of five B subunits carrying a single catalytically active A subunit. LTB binds the monosialoganglioside G(M1), the toxin's host receptor, but interactions with A-type blood sugars and E. coli lipopolysaccharide have also been identified within the past decade. Here, we review the regulation, assembly, and binding properties of the LT B-subunit pentamer and discuss the possible roles of its numerous molecular interactions.

HBHA and ESAT-6 induced IFN-g responses in M. tuberculosis infected subjects from a low incidence country

info:eu-repo/semantics/nonPublished

Open ended microwave oven for packaging

A novel open waveguide cavity resonator is presented for the combined variable frequency microwave curing of bumps, underfills and encapsulants, as well as the alignment of devices for fast flip-chip assembly, direct chip attach (DCA) or wafer-scale level packaging (WSLP). This technology achieves radio frequency (RF) curing of adhesives used in microelectronics, optoelectronics and medical devices with potential simultaneous micron-scale alignment accuracy and bonding of devices. In principle, the open oven cavity can be fitted directly onto a flip-chip or wafer scale bonder and, as such, will allow for the bonding of devices through localised heating thus reducing the risk to thermally sensitive devices. Variable frequency microwave (VFM) heating and curing of an idealised polymer load is numerically simulated using a multi-physics approach. Electro-magnetic fields within a novel open ended microwave oven developed for use in micro-electronics manufacturing applications are solved using a dedicated Yee scheme finite-difference time-domain (FDTD) solver. Temperature distribution, degree of cure and thermal stresses are analysed using an Unstructured Finite Volume method (UFVM) multi-physics package. The polymer load was meshed for thermophysical analysis, whilst the microwave cavity - encompassing the polymer load - was meshed for microwave irradiation. The two solution domains are linked using a cross mapping routine. The principle of heating using the evanescent fringing fields within the open-end of the cavity is demonstrated. A closed loop feedback routine is established allowing the temperature within a lossy sample to be controlled. A distribution of the temperature within the lossy sample is obtained by using a thermal imaging camera.

C. G. Jung and literary theory: the challenge from fiction

C.G. Jung and Literary Theory remedies a significant omission in literary studies by doing for Jung and poststructuralist literary theories what has been done extensively for Freud, Lacan and post-Freudian psychoanalysis. This work represents a complete departure from traditional Jungian literary criticism. Instead, radically new Jungian literary theories are developed of deconstruction, feminist theory, gender and psyche, the body and sexuality, spirituality, postcolonialism, historicism and reader-response. As well as linking Jung to the work of Derrida, Kristeva and Irigaray, the book traces contentious occult, cultural and political narratives in Jung's career. It contains a chapter on Jung and fascism in a literary context. [From the Publisher]