PI3P signaling regulates receptor sorting but not transport in the endosomal pathway

While evidence is accumulating that phosphoinositide signaling plays a crucial role in growth factor and hormone receptor down-regulation, this signaling pathway has also been proposed to regulate endosomal membrane transport and multivesicular endosome biogenesis. Here, we have followed the fate of the down-regulated EGF receptor (EGFR) and bulk transport (fluid phase) markers in the endosomal pathway in vivo and in vitro. We find that bulk transport from early to late endosomes is not affected after inhibition of the phosphatidylinositol-3-phosphate (PI3P) signaling pathway, but that the EGFR then remains trapped in early endosomes. Similarly, we find that hepatocyte growth factor–regulated tyrosine kinase substrate (Hrs) is not directly involved in bulk solute transport, but is required for EGFR sorting. These observations thus show that transport and sorting can be uncoupled in the endosomal pathway. They also show that PI3P signaling does not regulate the core machinery of endosome biogenesis and transport, but controls the sorting of down-regulated receptor molecules in early endosomes via Hrs

Mobilisation of an international Urban Search and Rescue team

This project aims to create context surrounding the field of disaster management and the structures functioning within this specified field. This document aims to outline a detailed plan on assisting a Non-Governmental Organisation, Rescue South Africa, in improving its reaction time with regards to disaster response. Due to natural disasters becoming more powerful, it has a pronounced effect on people living in disaster prone areas. One of the critical phases of disaster management is the Response phase. This is the phase in which Rescue South Africa predominantly functions. This project will focus on the mobilisation phase of disaster response. Critical to mobilisation is securing a structured mobilisation plan, customised for the South African environment. Another crucial aspect of mobilisation is assembling the team with the correct competencies to respond to the unannounced disaster. Following this methodology, solutions are presented. In order to aid the development of the structured mobilisation plan, business process mapping is employed. A team composition strategy used for the selection of soccer players is utilised to select the best USAR technicians for a specified disaster scenario.Thesis (B Eng. (Industrial and Systems Engineering))--University of Pretoria, 2012

From policy to pedagogy: widening the discourse and practice of the learning society in the European Union

This paper explores the policy turn of the learning society, and how the academic world is responding to new social and political demands. It highlights some of the criticisms levelled at the learning society, as well as the voices of support. The paper also showcases the European Language Portfolio and the Transferable Skills project as two examples of good practice. Cet article examine le tournant de la politique de la socie´te´ du savoir ainsi que la re´ponse du monde intellectuel face aux nouvelles exigences sociales et politiques. Il met en lumie`re certaines des critiques souleve´es par la socie´te´ du savoir ainsi que par les voix favorables. L’article s’appuie sur deux exemples pratiques, a` savoir le Portfolio Europe´en des Langues et le Project des Compe´tences Transmissibles

Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.

Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization

Changes in the arabinoxylan fraction of wheat grain during 1 alcohol production

Laboratory produced DDGS samples were compared with commercial samples from a distillery and a biofuel plant. Changes in structure, solubility and content of arabinoxylan (AX) was determined. The distillation process results in a relative increase of AX content compared to the starting material. The heating and drying processes involved in the production of DDGS lead to an increased solubility and viscosity of water-extractable AX. Production of DDGS results in structural changes to the AX. There is a decrease in 2-and 3-linked arabinose oligosaccharides, that contributes to around a 50% reduction in arabinosylation in DDGS compared with the starting grains. The current study shows that laboratory-scale DDGS provide an accurate representation of the commercial scale and that the AX composition of DDGS is consistently uniform irrespective of starting material. The uniformity of DDGS and thin stillage makes them a good potential source of AX for production of prebiotics or other novel products

Ammonite stratigraphy of a Toarcian (Lower Jurassic) section on Nagy-Pisznice Hill (Gerecse Mts, Hungary)

Abstract In the Jurassic rocks exposed in a small abandoned quarry on the northwestern edge of Nagy-Pisznice Hill in the Gerecse Mts, fairly well preserved parts of a crocodile skeleton was found in 1996. The bed which yielded the skeletal remains is the uppermost layer of the Kisgerecse Marl Formation exposed here and was determined as belonging to the Upper Toarcian Grammoceras thouarsense Zone. The beds of the sequence above and below were carefully sampled in the late 1990s, and the encountered ammonites were evaluated biostratigraphically. As a result, the Lower Toarcian Harpoceras serpentinum Zone, the Middle Toarcian Hildoceras bifrons and Merlaites gradatus Zones, and the Upper Toarcian Grammoceras thouarsense and Geczyceras speciosum Zones were identified. Within most of these zones the subzones and even the faunal horizons were successfully recognized. The lowermost beds above the underlying Pliensbachian red limestone did not yield any fossils; thus the lowermost Toarcian Dactylioceras tenuicostatum Zone could not be documented. The highest Toarcian ammonite zones also remained unidentified, because the beds of the Tölgyhát Limestone above were not sampled all the way up. This paper presents the lithostratigraphic and biostratigraphic details of the sequence, and the paleontological descriptions of the most important ammonites

Tmetoceratidae (Ammonitina) fauna from the Gerecse Mts (Hungary)

Abstract Taxonomic and stratigraphic problems of the family Tmetoceratidae and the genera Dumortieria, Catulloceras, Cotteswoldia, Pleydellia and Tmetoceras included in it are briefly discussed. Fifteen species of Tmetoceratidae are described and illustrated from the Upper Toarcian-Aalenian ammonite assemblages of the Gerecse Mts (NE Transdanubian Range, Hungary). The fauna described here is closely allied to the Mediterranean Province of the Mediterranean-Caucasian Realm

Boolean dynamics revisited through feedback interconnections

Boolean models of physical or biological systems describe the global dynamics of the system and their attractors typically represent asymptotic behaviors. In the case of large networks composed of several modules, it may be difficult to identify all the attractors. To explore Boolean dynamics from a novel viewpoint, we will analyse the dynamics emerging from the composition of two known Boolean modules. The state transition graphs and attractors for each of the modules can be combined to construct a new asymptotic graph which will (1) provide a reliable method for attractor computation with partial information; (2) illustrate the differences in dynamical behavior induced by the updating strategy (asynchronous, synchronous, or mixed); and (3) show the inherited organization/structure of the original network’s state transition graph.publishe

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis