Integrin affinity modulation and survival signalling.

Integrins are heterodimeric transmembrane proteins that provide a bi-directional link between the cell’s internal biological mechanisms and the extracellular environment. During inside-out signalling, intracellular messages converge on the integrin cytoplasmic domain to induce a conformational change. This is transmitted to the extracellular domain where it results in an alteration in affinity for integrin ligands such as fibronectin and laminin. In this way the cell has developed the ability to modulate the critical functions of adhesion and cell movement. In outside-in signalling, the integrin performs a more complex function than simple adhesion; upon binding to ligand, the integrin extracellular domain undergoes a conformational change which is transmitted to the cytoplasmic domain. This alters the integrin’s cytoplasmic domain affinity for intracellular signalling proteins and results in the activation of intracellular second messenger pathways. In this way, the extracellular milieu is able to influence intracellular signalling including those involved in apoptosis. This thesis demonstrates data which provide original insights into bi-directional integrin signalling: Inside-out signalling: Constitutively active Notch1 increases β3-integrin affinity and abrogates Hras-mediated integrin suppression without increasing expression of β3- integrin. Dominant-Negative Rras blocks Notch-mediated integrin activation and Notch1-mediated reversal of Hras and Raf-mediated integrin suppression and this is independent of erk phosphorylation. Notch1 induces Rras activation. Functional adhesion assays confirm that Notch1IC increases K562 adhesion in a β1-integrin dependent manner and this is abrogated by Dominant-Negative Rras. This data supports a mechanism in which Notch1 increases integrin affinity via activation of Rras. Outside-in signalling: Evidence is presented demonstrating that extracellular matrix proteins, laminin and fibronectin, activate β1-integrins to protect SCLC cells against the apoptotic effects of etoposide and ionizing radiation via PI3Kinase activation. This occurs in two ways: 1) PI3Kinase-dependent β1-integrin signalling resulting in phosphorylation of Bad and reduced caspase-9 cleavage and 2) a β1-integrinmediated over-riding of etoposide and radiotherapy-induced cell cycle S phase delay and G2/M arrest. β1-integrin-mediated outside-in survival signalling was investigated further in the in vivo setting; MatrigelTM, a basement membrane product rich in extracellular matrix proteins, promoted SCLC xenograft survival and growth in a β1-integrin and tyrosine kinase-dependent manner. This data provides novel insights into the critical functions that integrins play in adhesion and survival signalling

Champagne: Automated Whole-Genome Phylogenomic Character Matrix Method Using Large Genomic Indels for Homoplasy-Free Inference.

We present Champagne, a whole-genome method for generating character matrices for phylogenomic analysis using large genomic indel events. By rigorously picking orthologous genes and locating large insertion and deletion events, Champagne delivers a character matrix that considerably reduces homoplasy compared with morphological and nucleotide-based matrices, on both established phylogenies and difficult-to-resolve nodes in the mammalian tree. Champagne provides ample evidence in the form of genomic structural variation to support incomplete lineage sorting and possible introgression in Paenungulata and human-chimp-gorilla which were previously inferred primarily through matrices composed of aligned single-nucleotide characters. Champagne also offers further evidence for Myomorpha as sister to Sciuridae and Hystricomorpha in the rodent tree. Champagne harbors distinct theoretical advantages as an automated method that produces nearly homoplasy-free character matrices on the whole-genome scale

Sustainability in the Fashion brands websites: SEO keywords density analysis and consumers' behaviour

Sustainability is becoming one of the main trends within our society and there is the need to combine this value within fashion. The fashion industry is one of the leading industries which produces the highest amount of pollution in the world. The production requires an immense use of water and chemicals and the pollution created with the textile waste has a tremendous negative impact on the environment. Integrating sustainability, as a value within the fashion system, can be challenging; therefore, the perception towards sustainability has to be positive, has to be an opportunity. Online communication is crucial to influence customers and to deliver sustainable purchase behaviour. SEO keywords density analysis studies how fashion websites are implementing their online communication toward sustainability, focusing on specific keywords. The author chose keywords from previous literature and through online software which suggests the most similar keywords to the word “sustainability” and “sustainable fashion” used online. The objective of this paper is to observe and analyse the online keywords of fashion brands websites concerning sustainability. I plan to research its significance, taking into consideration the growing online marketplace. Keywords: sustainable, fashion, online, website, keyword

Human protein reference database as a discovery resource for proteomics

The rapid pace at which genomic and proteomic data is being generated necessitates the development of tools and resources for managing data that allow integration of information from disparate sources. The Human Protein Reference Database (http://www.hprd.org) is a web-based resource based on open source technologies for protein information about several aspects of human proteins including protein–protein interactions, post-translational modifications, enzyme–substrate relationships and disease associations. This information was derived manually by a critical reading of the published literature by expert biologists and through bioinformatics analyses of the protein sequence. This database will assist in biomedical discoveries by serving as a resource of genomic and proteomic information and providing an integrated view of sequence, structure, function and protein networks in health and disease