Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes

Ubiquitination involves the attachment of ubiquitin (Ub) to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Polyubiquitination through different lysines (seven) or the N-terminus of Ub can generate different protein-Ub structures. These include monoubiquitinated proteins, polyubiqutinated proteins with homotypic chains through a particular lysine on Ub or mixed polyubiquitin chains generated by polymerization through different Ub lysines. The ability of the ubiquitination pathway to generate different protein-Ub structures provides versatility of this pathway to target proteins to different fates. Protein ubiquitination is catalyzed by Ub-conjugating and Ub-ligase enzymes, with different combinations of these enzymes specifying the type of Ub modification on protein substrates. How Ub-conjugating and Ub-ligase enzymes generate this structural diversity is not clearly understood. In the current review, we discuss mechanisms utilized by the Ub-conjugating and Ub-ligase enzymes to generate structural diversity during protein ubiquitination, with a focus on recent mechanistic insights into protein monoubiquitination and polyubiquitination.

Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.

Socio-structural influences on the work participation of refugees : an exploratory systematic mixed studies review

This systematic mixed studies review aimed at synthesizing evidence from studies related to the influences on the work participation of people with refugee status (PWRS). The review focused on the role of proximal socio-structural barriers on work participation by PWRS while foregrounding related distal, intermediate, proximal, and meta-systemic influences. For the systematic search of the literature, we focused on databases that addressed work, well-being, and social policy in refugee populations, including, Medline, CINAHL, PsycInfo, Web of Science, Scopus, and Sociological Abstracts. Of the studies reviewed, 16 of 39 met the inclusion criteria and were retained for the final analysis. We performed a narrative synthesis of the evidence on barriers to work participation by PWRS, interlinking clusters of barriers potent to their effects on work participation. Findings from the narrative synthesis suggest that proximal factors, those at point of entry to the labor market, influence work participation more directly than distal or intermediate factors. Distal and intermediate factors achieve their effects on work participation by PWRS primarily through meta-systemic interlinkages, including host-country documentation and refugee administration provisions.

Reliable and valid survey design for structural equation modelling

My quantitative study asks how Chinese Australians’ “Chineseness” and their various resources influence their Chinese language proficiency, using online survey and snowball sampling. ‘Operationalization’ is a challenging process which ensures that the survey design talks back to the informing theory and forwards to the analysis model. It requires the attention to two core methodological concerns, namely ‘validity’ and ‘reliability’. Construction of a high-quality questionnaire is critical to the achievement of valid and reliable operationalization. A series of strategies were chosen to ensure the quality of the questions, and thus the eventual data. These strategies enable the use of structural equation modelling to examine how well the data fits the theoretical framework, which was constructed in light of Bourdieu’s theory of habitus, capital and field.

Molecular and structural requirements of the ß1L-adrenoceptor

Noradrenaline which occurs naturally in the body binds to beta-adrenoceptors on the heart, causing the heart to beat faster and with greater force in response to increased demand. This enables the heart to provide oxygenated blood to vital organs. Prolonged overstimulation by noradrenaline can be harmful to the heart and lead to the progression of heart disease. In these circumstances beta-adrenoceptors are blocked with drugs called beta-blockers. Beta-blockers block the effects of noradrenaline by binding to the same site on the beta-adrenoceptor. Some beta-blockers such as CGP12177 can also cause increases in heart rate. Therefore it was proposed that CGP12177 could bind in a different place to noradrenaline. The aim of this study was to determine where CGP12177 binds to on the beta-adrenoceptor. The results have revealed a separate binding site named beta-1-low. These results may lead to the development of improved -blockers for the management of heart conditions.

Towards a typology of structural arrangements for shared services : evidence from the higher education sector

Shared services are increasingly prevalent in practice, their introduction potentially entailing substantive and highly consequential organizational redesign. Yet, attention to the structural arrangements of shared services has been limited. This study explores types of structural arrangements for shared services that are observed in practice, and the salient dimensions along which those types can be usefully differentiated. Through inductive attention to the shared services literature, and content analysis of 36 secondary case studies of shared services in the higher education sector, three salient dimensions emerged: (1) the existence or not of a separate organizational entity, (2) an intra- or inter-organizational sharing boundary, and (3) involvement or not of a third party. Each dimension being dichotomous yields 23 combinations, or eight shared services structural arrangement types. Each of the eight structural arrangement types is defined and demonstrated through case examples. The typology offers clarity around shared services structural arrangements. It can serve as a useful analytical tool for researchers investigating the phenomenon further, and for practitioners considering the introduction or further development of shared services arrangements. Important follow on research is suggested too.

Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography

Ebola virus is a highly pathogenic filovirus causing severe hemorrhagic fever with high mortality rates. It assembles heterogenous, filamentous, enveloped virus particles containing a negative-sense, single-stranded RNA genome packaged within a helical nucleocapsid (NC). We have used cryo-electron microscopy and tomography to visualize Ebola virus particles, as well as Ebola virus-like particles, in three dimensions in a near-native state. The NC within the virion forms a left-handed helix with an inner nucleoprotein layer decorated with protruding arms composed of VP24 and VP35. A comparison with the closely related Marburg virus shows that the N-terminal region of nucleoprotein defines the inner diameter of the Ebola virus NC, whereas the RNA genome defines its length. Binding of the nucleoprotein to RNA can assemble a loosely coiled NC-like structure; the loose coil can be condensed by binding of the viral matrix protein VP40 to the C terminus of the nucleoprotein, and rigidified by binding of VP24 and VP35 to alternate copies of the nucleoprotein. Four proteins (NP, VP24, VP35, and VP40) are necessary and sufficient to mediate assembly of an NC with structure, symmetry, variability, and flexibility indistinguishable from that in Ebola virus particles released from infected cells. Together these data provide a structural and architectural description of Ebola virus and define the roles of viral proteins in its structure and assembly

Anatomical MR imaging of long bones : comparative performance of MRI at 1.5 T and 3 T

The current gold standard for the design of orthopaedic implants is 3D models of long bones obtained using computed tomography (CT). However, high-resolution CT imaging involves high radiation exposure, which limits its use in healthy human volunteers. Magnetic resonance imaging (MRI) is an attractive alternative for the scanning of healthy human volunteers for research purposes. Current limitations of MRI include difficulties of tissue segmentation within joints and long scanning times. In this work, we explore the possibility of overcoming these limitations through the use of MRI scanners operating at a higher field strength. We quantitatively compare the quality of anatomical MR images of long bones obtained at 1.5 T and 3 T and optimise the scanning protocol of 3 T MRI. FLASH images of the right leg of five human volunteers acquired at 1.5 T and 3 T were compared in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The comparison showed a relatively high CNR and SNR at 3 T for most regions of the femur and tibia, with the exception of the distal diaphyseal region of the femur and the mid diaphyseal region of the tibia. This was accompanied by an ~65% increase in the longitudinal spin relaxation time (T1) of the muscle at 3 T compared to 1.5 T. The results suggest that MRI at 3 T may be able to enhance the segmentability and potentially improve the accuracy of 3D anatomical models of long bones, compared to 1.5 T. We discuss how the total imaging times at 3 T can be kept short while maximising the CNR and SNR of the images obtained.

Thermogravimetric analysis, PXRD, EDX and XPS study of chrysocolla (Cu,Al)2H2Si2O5(OH)4·nH2O : structural implications

Selected chrysocolla mineral samples from different origins have been studied by using PXRD, SEM, EDX and XPS. The XRD patterns show that the chrysocolla mineral samples are non-diffracting and no other phases are present in the minerals, thus showing the chrysocolla samples are pure. SEM analyses show the chrysocolla surfaces are featureless. EDX analyses enable the formulae of the chrysocolla samples to be calculated. The thermal decomposition of the mineral chrysocolla has been studied using a combination of thermogravimetric analysis and derivative thermogravimetric analysis. Five thermal decomposition mass loss steps are observed for the chrysocolla from Arizona (a) at 125 ◦C with the loss of water, (b) at 340 ◦C with the loss of hydroxyl units, (c) at 468.5 ◦C with a further loss of hydroxyls, (d) at 821 ◦C with oxygen loss and (e) at 895 ◦C with a further loss of oxygen. The thermal analysis of the chrysocolla from Congo shows mass losses at 125, 275.3, 805.6 and 877.4 ◦C and for the Nevada chrysocolla, mass loss steps at 268, 333, 463, 786.0 and 817.7 ◦C are observed. The thermal analysis of spertiniite is very different from that of chrysocolla and thermally decomposes at around 160 ◦C. XPS shows that there are two different copper species present, one which is bonded to oxygen and one to a hydroxyl unit. The O 1s is broad and very symmetrical suggesting two O species of equal number. The bond energy of 102.9 eV for the Si 2p suggests that it is in the form of a silicate. The bond energy is much higher for silicas around ∼103.5 eV. The reported value for silica gel has Si 2p at 103.4 eV. The combination of TG, PXRD, EDX and XPS adds to our fundamental knowledge of the structure of chrysocolla.

Performance characterization of VGCF/epoxy nanocomposite sensors under static load cycles and in static structural health monitoring

Compared to conventional metal-foil strain gauges, nanocomposite piezoresistive strain sensors have demonstrated high strain sensitivity and have been attracting increasing attention in recent years. To fulfil their ultimate success, the performance of vapor growth carbon fiber (VGCF)/epoxy nanocomposite strain sensors subjected to static cyclic loads was evaluated in this work. A strain-equivalent quantity (resistance change ratio) in cantilever beams with intentionally induced notches in bending was evaluated using the conventional metal-foil strain gauges and the VGCF/epoxy nanocomposite sensors. Compared to the metal-foil strain gauges, the nanocomposite sensors are much more sensitive to even slight structural damage. Therefore, it was confirmed that the signal stability, reproducibility, and durability of these nanocomposite sensors are very promising, leading to the present endeavor to apply them for static structural health monitoring.

A hierarchical structural model of assessing innovation and project performance

Research in construction innovation highlights construction industry as having many barriers and resistance to innovations and suggests that it needs champions. A hierarchical structural model is presented, to assess the impact of the role of the project manager (PM) on the levels of innovation and project performance. The model adopts the structural equation modelling technique and uses the survey data collected from PMs and project team members working for general contractors in Singapore. The model fits well to the observed data, accounting for 24%, 37% and 49% of the variance in championing behaviour, the level of innovation and project performance, respectively. The results of this study show the importance of the championing role of PMs in construction innovation. However, in order to increase their effectiveness, such a role should be complemented by their competency and professionalism, tactical use of influence tactics, and decision authority. Moreover, senior management should provide adequate resources and a sustained support to innovation and create a conducive environment or organizational culture that nurtures and facilitates the PM’s role in the construction project as a champion of innovation.

A vibrational spectroscopic study of philipsbornite PbAl3(AsO4)2(OH)5⋅H2O-molecular structural implications and relationship to the crandallite subgroup arsenates

The presence of arsenic in the environment is a hazard. The accumulation of arsenate by a range of cations in the formation of minerals provides a mechanism for the remediation of arsenate contamination. The formation of the crandallite group of minerals provides a mechanism for arsenate accumulation. Among the crandallite minerals are philipsbornite, arsenocrandallite and arsenogoyazite. Raman spectroscopy complimented with infrared spectroscopy has enabled aspects of the structure of philipsbornite to be studied. The Raman spectrum of philipsbornite displays an intense band at around 840 cm−1 attributed to the overlap of the symmetric and antisymmetric stretching modes. Raman bands observed at 325, 336, 347, 357, 376 and 399 cm−1 are assigned to the ν2 (AsO4)3− symmetric bending vibration (E) and to the ν4 bending vibration (F2). The observation of multiple bending modes supports the concept of a reduction in symmetry of the arsenate anion in philipsbornite. Evidence for phosphate in the mineral is provided. By using an empirical formula, hydrogen bond distances for the OH units in philipsbornite of 2.8648 Å, 2.7864 Å, 2.6896 Å cm−1 and 2.6220 were calculated.

Structural characterisation and environmental application of organoclays for the removal of phenolic compounds

Modified montmorillonite was prepared at different surfactant (HDTMA) loadings through ion exchange. The conformational arrangement of the loaded surfactants within the interlayer space of MMT was obtained by computational modelling. The conformational change of surfactant molecules enhance the visual understanding of the results obtained from characterization methods such as XRD and surface analysis of the organoclays. Batch experiments were carried out for the adsorption of p-chlorophenol (PCP) and different conditions (pH and temperature) were used in order to determine the optimum sorption. For comparison purpose, the experiments were repeated under the same conditions for p-nitrophenol (PNP). Langmuir and Freundlich equations were applied to the adsorption isotherm of PCP and PNP. The Freundlich isotherm model was found to be the best fit for both of the phenolic compounds. This involved multilayer adsorptions in the adsorption process. In particular, the binding affinity value of PNP was higher than that of PCP and this is attributable to their hydrophobicities. The adsorption of the phenolic compounds by organoclays intercalated with highly loaded surfactants was markedly improved possibly due to the fact that the intercalated surfactant molecules within the interlayer space contribute to the partition phases, which result in greater adsorption of the organic pollutants.

Structural and textural variations in carbonaceous chondrite matrices

Recent studies of C2 carbonaceous chondrite matrices using high resolu­tion transmission electron microscopy (HRTEM)have shown that structural details of the matrix minerals can be imaged [1-4]. The Murchison and Mighei matrices contain minerals having ordered and disordered mixed-layer structures [1,3,4] in addition to chrysotile- and lizardite-type structures [2].

Experimental investigation of the governing parameters in the electrospinning of poly(3-hydroxybutyrate) scaffolds : structural characteristics of the pores

We sought to determine the impact of electrospinning parameters on a trustworthy criterion that could evidently improve the maximum applicability of fibrous scaffolds for tissue regeneration. We used an image analysis technique to elucidate the web permeability index (WPI) by modeling the formation of electrospun scaffolds. Poly(3-hydroxybutyrate) (P3HB) scaffolds were fabricated according to predetermined conditions of levels in a Taguchi orthogonal design. The material parameters were the polymer concentration, conductivity, and volatility of the solution. The processing parameters were the applied voltage and nozzle-to-collector distance. With a law to monitor the WPI values when the polymer concentration or the applied voltage was increased, the pore interconnectivity was decreased. The quality of the jet instability altered the pore numbers, areas, and other structural characteristics, all of which determined the scaffold porosity and aperture interconnectivity. An initial drastic increase was observed in the WPI values because of the chain entanglement phenomenon above a 6 wt % P3HB content. Although the solution mixture significantly (p < 0.05) changed the scaffold architectural characteristics as a function of the solution viscosity and surface tension, it had a minor impact on the WPI values. The solution mixture gained the third place of significance, and the distance was approved as the least important factor.