Patterned thin film cathodes for micro-solid oxide fuel cells

Imperial Users onl

The Popeye Domain Containing Genes and cAMP Signaling.

3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins

The cAMP-binding Popdc proteins have a redundant function in the heart

Popdc (Popeye-domain-containing) genes encode membrane-bound proteins and are abundantly present in cardiac myocytes and in skeletal muscle fibres. Functional analysis of Popdc1 (Bves) and Popdc2 in mice and of popdc2 in zebrafish revealed an overlapping role for proper electrical conduction in the heart and maintaining structural integrity of skeletal muscle. Popdc proteins mediate cAMP signalling and modulate the biological activity of interacting proteins. The two-pore channel TREK-1 interacts with all three Popdc proteins. In Xenopus oocytes, the presence of Popdc proteins causes an enhanced membrane transport leading to an increase in TREK-1 current, which is blocked when cAMP levels are increased. Another important Popdc-interacting protein is caveolin 3, and the loss of Popdc1 affects caveolar size. Thus a family of membrane-bound cAMP-binding proteins has been identified, which modulate the subcellular localization of effector proteins involved in organizing signalling complexes and assuring proper membrane physiology of cardiac myocytes

Gli3 Controls Corpus Callosum Formation by Positioning Midline Guideposts During Telencephalic Patterning

The corpus callosum (CC) represents the major forebrain commissure connecting the 2 cerebral hemispheres. Midline crossing of callosal axons is controlled by several glial and neuronal guideposts specifically located along the callosal path, but it remains unknown how these cells acquire their position. Here, we show that the Gli3 hypomorphic mouse mutant Polydactyly Nagoya (Pdn) displays agenesis of the CC and mislocation of the glial and neuronal guidepost cells. Using transplantation experiments, we demonstrate that agenesis of the CC is primarily caused by midline defects. These defects originate during telencephalic patterning and involve an up-regulation of Slit2 expression and altered Fgf and Wnt/β-catenin signaling. Mutations in sprouty1/2 which mimic the changes in these signaling pathways cause a disorganization of midline guideposts and CC agenesis. Moreover, a partial recovery of midline abnormalities in Pdn/Pdn;Slit2(-/-) embryos mutants confirms the functional importance of correct Slit2 expression levels for callosal development. Hence, Gli3 controlled restriction of Fgf and Wnt/β-catenin signaling and of Slit2 expression is crucial for positioning midline guideposts and callosal development

Identification and functional analysis of pronephric development genes in Xenopus laevis

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Identification and functional analysis of pronephric development genes in Xenopus laevis

The formation of the kidney in vertebrates proceeds through a succession of up to three structures, the pronephros, metanephros and mesonephros. This project aimed to identify a suitable target gene involved in the development of the pronephros and study its role in development. By analysing the functional role of a target gene. this thesis ultimately aims to further elucidate the developmental regulation of pronephric organogenesis. The candidate target genes were identified from 3 sources. Firstly. a Xenopus laevis stage 13 cDNA library was screened using a probe made from retinoic acid and activin A treated animal caps. Secondly. four UniGene cluster genes were investigated. after initial analysis indicated they were highly pronephros specific (Personal correspondence Pollet, N). Finally, data mining identified Xenopus homologues of important kidney development genes identified in higher vertebrates or newly identified genes expressed in the pronephros. On the basis of preliminary data, Darmin r and Pod I were taken forward for functional studies. Pod I, a basic-helix-loop-helix transcription factor, was found to be expressed from pronephric initiation with enhanced expression in the pronephros. The expression patterns of Pod I strongly matched that of the mouse homologue, implying a conserved evolutionary role. Pronephros targeted over-expression resulted in the reduction of glomus tissue, with no alteration in pronephric tubule or duct morphology. In addition, targeted knock-down resulted in the absence of cells in the glomus region. Preliminary analysis of Darmin r, a cytosolic non-specific dipeptidase. indicated a role later in pronephric tubule development. Targeted over-expression experiments disrupted tubule morphology and reduced the size of the pronephric anlagen. Initial promising data clearly placed Pod I and Darmin r as important pronephric development genes

Patterned thin film cathodes for micro-solid oxide fuel cells

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

What is research funding, how does it influence research, and how is it recorded? Key dimensions of variation

Evaluating the effects of some or all academic research funding is difficult because of the many different and overlapping sources, types, and scopes. It is therefore important to identify the key aspects of research funding so that funders and others assessing its value do not overlook them. This article outlines 18 dimensions through which funding varies substantially, as well as three funding records facets. For each dimension, a list of common or possible variations is suggested. The main dimensions include the type of funder of time and equipment, any funding sharing, the proportion of costs funded, the nature of the funding, any collaborative contributions, and the amount and duration of the grant. In addition, funding can influence what is researched, how and by whom. The funding can also be recorded in different places and has different levels of connection to outputs. The many variations and the lack of a clear divide between “unfunded” and funded research, because internal funding can be implicit or unrecorded, greatly complicate assessing the value of funding quantitatively at scale. The dimensions listed here should nevertheless help funding evaluators to consider as many differences as possible and list the remainder as limitations. They also serve as suggested information to collect for those compiling funding datasets