350 research outputs found

    The adoption of the European System of Accounts 1995 framework in the national accounts of Malta

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    The release of ESA 1995 GDP data for Malta has ushered in great changes in the way in which the Maltese economy can be analysed. Indicators computed from the new national accounts reveal that the Maltese economy has achieved a relatively high degree of convergence with the European average, especially when compared with other new Member States. However some industries which are less subject to competitive pressures under-perform compared with their European counterparts, while employment rates remain very low.national accounts, productivity, sectoral analysis

    Towards the Chemical Control of Membrane Protein Function

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    Thesis advisor: Jianmin GaoThe oligomerization of membrane proteins has been shown to play a critical role in a myriad of cellular processes, some of which include signal propagation, cell-to-cell communication, and a cell's ability to interact with its surroundings. Diseases that are associated with disruption of protein-protein interactions in the membrane include cystic fibrosis, certain cancers, and bone growth disorders. Although significant progress has been made in our mechanistic understanding of protein-protein interactions in membranes, it remains difficult to predict the oligomerization state of transmembrane domains and explain the physiological consequences of a point mutation within a membrane embedded protein. The development of novel classes of chemical tools will allow us to better understand the energetics of transmembrane domain association at the molecular level. Herein, we demonstrate that fluorinated aromatic amino acids offer intriguing potential as chemical mediators of transmembrane protein association. We have systematically examined the effects of fluorination on the physical properties of aromatic systems in the context of a soluble protein model system. Our results illustrate the ability of fluorinated aromatic amino acids to simultaneously stabilize protein structure and facilitate highly specific protein self-assembly. An improved understanding of the fundamental energetics of aromatic interactions should allow for their more efficient incorporation into designed inhibitors of transmembrane protein association. In addition to chemical tools, the development of simple methods for directly monitoring transmembrane domain association in vitro and in vivo is necessary to advance our understanding of these interactions. Towards this goal, we have established FlAsH-tetracysteine display as an effective approach to quantifying the association propensities of transmembrane α-helices (TMHs) in vitro. Our assay is compatible with two of the most commonly utilized model membrane systems, detergent micelles and vesicles. The high spatial resolution of FlAsH binding (˂ 10 Å) allows for the differentiation of parallel and antiparallel oligomerization events. Importantly, preliminary studies suggest the assay's ability to detect inhibition from exogenous TMHs. Encouraged by our understanding of aromatic interactions and the success of our assay, we are beginning to incorporate fluorinated aromatics in the model TMHs and monitoring their ability to associate. The ultimate goal is to modulate the association of endogenous TMHs such as ErbB2. Research in this direction is ongoing.Thesis (PhD) — Boston College, 2013.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry

    The adoption of the European System of Accounts 1995 framework in the national accounts of Malta

    Get PDF
    The release of ESA 1995 GDP data for Malta has ushered in great changes in the way in which the Maltese economy can be analysed. Indicators computed from the new national accounts reveal that the Maltese economy has achieved a relatively high degree of convergence with the European average, especially when compared with other new Member States. However some industries which are less subject to competitive pressures under-perform compared with their European counterparts, while employment rates remain very low

    The adoption of the European System of Accounts 1995 framework in the national accounts of Malta

    Get PDF
    The release of ESA 1995 GDP data for Malta has ushered in great changes in the way in which the Maltese economy can be analysed. Indicators computed from the new national accounts reveal that the Maltese economy has achieved a relatively high degree of convergence with the European average, especially when compared with other new Member States. However some industries which are less subject to competitive pressures under-perform compared with their European counterparts, while employment rates remain very low

    Identification of an HNF1A p.Gly292fs frameshift mutation presenting as diabetes during pregnancy in a Maltese family

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    The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α (HNF1A) are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of HNF1A that lies within a known mutational hotspot in this gene. In this report, we provide the first description of an HNF1A-MODY3 phenotype in a Maltese family. The findings reported are relevant and new to a regional population, where the epidemiology of atypical diabetes has never been studied before. This report is of clinical interest as it highlights how monogenic diabetes can be misdiagnosed as either type 1, type 2, or gestational diabetes. It also reinforces the need for a better characterisation of monogenic diabetes in Mediterranean countries, particularly in island populations such as Malta with a high prevalence of diabetes.peer-reviewe

    Clinical effects of natalizumab on multiple sclerosis appear early in treatment course

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    In clinical practice natalizumab is typically used in patients who have experienced breakthrough disease during treatment with interferon beta (IFNβ) or glatiramer acetate. In these patients it is important to reduce disease activity as quickly as possible. In a phase II study, differences between natalizumab and placebo in MRI outcomes reflecting inflammatory activity were evident after the first infusion and maintained through a 6-month period, suggesting a rapid onset of natalizumab treatment effects. To explore how soon after natalizumab initiation clinical effects become apparent, annualized relapse rates per 3-month period and time to first relapse were analyzed in the phase III AFFIRM study (natalizumab vs. placebo) and in the multinational Tysabri® Observational Program (TOP). In AFFIRM, natalizumab reduced the annualized relapse rate within 3months of treatment initiation compared with placebo in the overall population (0.30 vs. 0.71; p<0.0001) and in patients with highly active disease (0.30 vs. 0.94; p=0.0039). The low annualized relapse rate was maintained throughout the 2-year study period, and the risk of relapse in AFFIRM patients treated with natalizumab was reduced [hazard ratio against placebo 0.42 (95% CI 0.34-0.52); p<0.0001]. Rapid reductions in annualized relapse rate also occurred in TOP (baseline 1.99 vs. 0-3months 0.26; p<0.0001). Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice. This decrease in disease activity occurred within the first 3months of treatment even in patients with more active diseas

    Effect of dietary fatty acid composition on depot fat and exercise performance in a migrating songbird, the red-eyed vireo

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    Most migrating birds accumulate lipid stores as their primary source of energy for fueling long distance flights. Lipid stores of birds during migration are composed of mostly unsaturated fatty acids; whether such a fatty acid composition enhances exercise performance of birds is unknown. We tested this hypothesis by measuring metabolic rate at rest and during intense exercise in two groups of red-eyed vireos, a long-distance migratory passerine, fed either a diet containing 82% unsaturated fat (82%U), or one containing 58% unsaturated fat (58%U). Vireos fed the 82%U diet had fat stores containing (77%) unsaturated fatty acids, whereas vireos fed the 58% U diet had fat stores containing less (66%) unsaturated fatty acids. Blood metabolites measured prior to and immediately following exercise confirmed that vireos were metabolizing endogenous fat during intense exercise. Mass-specific resting metabolic rate (RMR) was similar for vireos fed the 58%U diet (2.75±0.32 ml O2 g–1 h–1) and for vireos fed the 82%U diet (2.30±0.30 ml O2 g–1 h–1). However, mass-specific peak metabolic rate (MRpeak) was 25% higher in vireos fed the 58%U diet (28.55±1.47 ml O2 g–1 h–1) than in vireos fed the 82%U diet (21.50±1.76 ml O2 g–1 h–1). Such whole-animal energetic effects of fatty acid composition of birds suggest that the energetic cost of migration in birds may be affected by the fatty acid composition of the diet

    Synaptically activated burst-generating conductances may underlie a group-pacemaker mechanism for respiratory rhythm generation in mammals

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    Breathing, chewing, and walking are critical life-sustaining behaviors in mammals that consist essentially of simple rhythmic movements. Breathing movements in particular involve the diaphragm, thorax, and airways but emanate from a network in the lower brain stem. This network can be studied in reduced preparations in vitro and using simplified mathematical models that make testable predictions. An iterative approach that employs both in vitro and in silico models argues against canonical mechanisms for respiratory rhythm in neonatal rodents that involve reciprocal inhibition and pacemaker properties. We present an alternative model in which emergent network properties play a rhythmogenic role. Specifically, we show evidence that synaptically activated burst-generating conductances-which are only available in the context of network activity-engender robust periodic bursts in respiratory neurons. Because the cellular burst-generating mechanism is linked to network synaptic drive we dub this type of system a group pacemaker. © 2010 Elsevier B.V

    The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

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    Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved

    NASA Curation Preparation for Ryugu Sample Returned by JAXA's Hayabusa2 Mission

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    The NASA OSIRIS-REx and JAXA Hayabusa2 missions to near-Earth asteroids Bennu and Ryugu share similar mission goals of understanding the origins of primitive, organic-rich asteroids. Under an agreement between JAXA and NASA, there is an on-going and productive collaboration between science teams of Hayabusa2 and OSIRIS-REx missions. Under this agreement, a portion of each of the returned sample masses will be exchanged between the agencies and the scientific results of their study will be shared. NASAs portion of the returned Hayabusa2 sample, consisting of 10% of the returned mass, will be jointly separated by NASA and JAXA. The sample will be legally and physically transferred to NASAs dedicated Hayabusa2 curation facility at Johnson Space Center (JSC) no later than one year after the return of the Hayabusa2 sample to Earth (December 2020). The JSC Hayabusa2 curation cleanroom facility design has now been completed. In the same manner, JAXA will receive 0.5% of the total returned OSIRIS-REx sample (minimum required sample to return 60 g, maximum sample return capacity of 2 kg) from the rest of the specimen. No later than one year after the return of the OSIRIS-REx sample to Earth (September 2023), legal, physical, and permanent custody of this sample subset will be transferred to JAXA, and the sample subset will be brought to JAXAs Extraterrestrial Sample Curation Center (ESCuC) at Institute of Space and Astronautical Science, Sagamihara City Japan
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