Adhesion Plaques: Sites of Transmembrane Interaction between the Extracellular Matrix and the Actin Cytoskeleton

In this paper we review what is known about the organization of adhesion plaques, the regions where cells in culture adhere most tightly to the underlying substratum. These specialized areas of the plasma membrane serve as attachment sites for stress fibres. A major objective has been to determine how microfilament bundles are anchored at such regions. In their morphology and composition adhesion plaques resemble the adhesions fibroblasts make to the extracellular matrix. Some extracellular matrix components have been identified on the outside face of adhesion plaques. Within the plasma membrane of adhesion plaques, extracellular matrix receptors, such as the fibronectin receptor (integrin), have been identified. This transmembrane glycoprotein complex has been shown to bind the cytoplasmic protein talin, which, in turn, associates with vinculin. These proteins establish a transmembrane chain of attachment between the extracellular matrix and the cytoskeleton, although how the actin filaments interact with these components remains to be determined. Besides having a structural function, adhesion plaques may also be regions where regulatory signals are transmitted across the membrane. Consistent with this idea has been the finding that various tyrosine kinases and a calcium-dependent protease are concentrated at the cytoplasmic aspect of adhesion plaques. Furthermore, several adhesion plaque proteins become phosphorylated during cell transformation by Rous sarcoma virus. In future work it will be important to determine how such modifications affect the interactions of these proteins and the stability of adhesion plaques

Multispectral lensless digital holographic microscope: imaging MCF-7 and MDA-MB-231 cancer cell cultures

Digital holography is the process where an object’s phase and amplitude information is retrieved from intensity images obtained using a digital camera (e.g. CCD or CMOS sensor). In-line digital holographic techniques offer full use of the recording device’s sampling bandwidth, unlike off-axis holography where object information is not modulated onto carrier fringes. Reconstructed images are obscured by the linear superposition of the unwanted, out of focus, twin images. In addition to this, speckle noise degrades overall quality of the reconstructed images. The speckle effect is a phenomenon of laser sources used in digital holographic systems. Minimizing the effects due to speckle noise, removal of the twin image and using the full sampling bandwidth of the capture device aids overall reconstructed image quality. Such improvements applied to digital holography can benefit applications such as holographic microscopy where the reconstructed images are obscured with twin image information. Overcoming such problems allows greater flexibility in current image processing techniques, which can be applied to segmenting biological cells (e.g. MCF-7 and MDA-MB- 231) to determine their overall cell density and viability. This could potentially be used to distinguish between apoptotic and necrotic cells in large scale mammalian cell processes, currently the system of choice, within the biopharmaceutical industry

Measurement of the binding energy of ultracold 87Rb133Cs molecules using an offset-free optical frequency comb

We report the binding energy of Rb87Cs133 molecules in their rovibrational ground state measured using an offset-free optical frequency comb based on difference frequency generation technology. We create molecules in the absolute ground state using stimulated Raman adiabatic passage (STIRAP) with a transfer efficiency of 88%. By measuring the absolute frequencies of our STIRAP lasers, we find the energy-level difference from an initial weakly bound Feshbach state to the rovibrational ground state with a resolution of ∼5 kHz over an energy-level difference of more than 114THz; this lets us discern the hyperfine splitting of the ground state. Combined with theoretical models of the Feshbach-state binding energies and ground-state hyperfine structure, we determine a zero-field binding energy of h×114268135.24(4)(3)MHz. To our knowledge, this is the most accurate determination to date of the dissociation energy of a molecule

Trace elements in end-stage renal disease – unfamiliar territory to be revealed

Although associated with unfavorable outcomes in the general population, abnormal blood levels of various trace elements have not been consistently studied in the end-stage renal disease population (with the notable exception of aluminum). This is surprising, as the uremic patient treated by chronic dialysis loses one major route of trace element excretion and is exposed systematically to a foreign environment (the dialysis fluid) possibly contaminated with significant amounts of potential deleterious trace elements. Moreover, some biological important trace elements may be lost through the dialysis membrane. Most studies to date demonstrated significantly altered blood levels of trace elements in ESRD patients compared to healthy controls. However, the biological impact of these abnormalities in renal disease is largely unknown and should be clarified by future studies. A further step would be the design of well-controlled randomized interventional studies, examining the potential therapeutic benefit of supplementing one or more trace elements in ESRD patients, a population characterized by an impressive mortality due to cardiovascular, infectious and neoplasic disease

Youth, mobility and mobile phones in Africa: findings from a three-country study

he penetration of mobile phones into sub-Saharan Africa has occurred with amazing rapidity: for many young people, they now represent a very significant element of their daily life. This paper explores usage and perceived impacts among young people aged c. 9–18 years in three countries: Ghana, Malawi and South Africa. Our evidence comes from intensive qualitative research with young people, their parents, teachers and other key informants (in-depth interviews, focus groups and school essays) and a follow-up questionnaire survey administered to nearly 3000 young people in 24 study sites. The study was conducted in eight different sites in each country (i.e. urban, peri-urban, rural and remote rural sites in each of two agro-ecological zones), enabling comparison of experiences in diverse spatial contexts. The evidence, collected within a broader research study of child mobility, allows us to examine current patterns of usage among young people with particular attention to the way these are emerging in different locational contexts and to explore connections between young people's phone usage, virtual and physical mobilities and broader implications for social change. The issues of gender and inter-generational relations are important elements in this account

Sailing into the wind : new disciplines in Australian higher education

Much is made of the potential of lifelong learning for individuals and organisations. In this article we tend to make much less of it, certainly with respect to its use in universities to discipline academics. Nevertheless, we argue that academics now need to re-learn the positions they occupy and the stances they take in response to the marketisation of Australian universities. In particular, we suggest that the position of (pure) critique no longer commands attention in Australian contexts of higher education, although the paper does not suggest a disregard for a critical stance purely for the sake of participation. It is in understanding the interconnections between position and stance , and how they might be strategically performed during the everyday practices of academics, that a more promising way of engaging with the venalities of the market is envisaged; a strategy that could be described as \u27sailing into the wind\u27. In discussing these matters, the paper draws on semi-structured interviews with academics located in university faculties/departments/schools of education along Australia\u27s eastern seaboard

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS