171 research outputs found

    Особенности воздействия иммиграции на рынок труда развитых стран

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    GNA2091 of Neisseria meningitidis is a lipoprotein of unknown function that is included in the novel 4CMenB vaccine. Here, we investigated the biological function and the subcellular localization of the protein. We demonstrate that GNA2091 functions in the assembly of outer membrane proteins (OMPs) because its absence resulted in the accumulation of misassembled OMPs. Cell fractionation and protease accessibility experiments showed that the protein is localized at the periplasmic side of the outer membrane. Pulldown experiments revealed that it is not stably associated with the -barrel assembly machinery, the previously identified complex for OMP assembly. Thus, GNA2091 constitutes a novel outer membrane-based lipoprotein required for OMP assembly. Furthermore, its location at the inner side of the outer membrane indicates that protective immunity elicited by this antigen cannot be due to bactericidal or opsonic activity of antibodies

    Consumers discard a lot more food than widely believed : Estimates of global food waste using an energy gap approach and affluence elasticity of food waste

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    This work provides an internationally comparable consumer food waste dataset based on food availability, energy gap and consumer affluence. Such data can be used for constructing meaningful and internationally comparable metrics on food waste, such as those for Sustainable Development Goal 12. The data suggests that consumer food waste follows a linear-log relationship with consumer affluence and starts to emerge when consumers reach a threshold of approximately $6.70/day/capita level of expenditure. These findings also imply that most empirical models overestimate consumption by not accounting for the possibility of food waste in their analysis. The results also show that the most widely cited global estimate of food waste is underestimated by a factor greater than 2 (214 Kcal/day/capita versus 527 Kcal/day/capita). Comparison with estimates of US consumer food waste based on national survey data shows this approach can reasonably reproduce the results without needing extensive data from national surveys.</p

    Consumers discard a lot more food than widely believed: Estimates of global food waste using an energy gap approach and affluence elasticity of food waste

    Get PDF
    This work provides an internationally comparable consumer food waste dataset based on food availability, energy gap and consumer affluence. Such data can be used for constructing meaningful and internationally comparable metrics on food waste, such as those for Sustainable Development Goal 12. The data suggests that consumer food waste follows a linear-log relationship with consumer affluence and starts to emerge when consumers reach a threshold of approximately $6.70/day/capita level of expenditure. These findings also imply that most empirical models overestimate consumption by not accounting for the possibility of food waste in their analysis. The results also show that the most widely cited global estimate of food waste is underestimated by a factor greater than 2 (214 Kcal/day/capita versus 527 Kcal/day/capita). Comparison with estimates of US consumer food waste based on national survey data shows this approach can reasonably reproduce the results without needing extensive data from national surveys

    Structural Characterization of Outer Membrane Components of the Type IV Pili System in Pathogenic Neisseria

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    Structures of the type IV pili secretin complexes from Neisseria gonorrhoeae and Neisseria meningitidis, embedded in outer membranes were investigated by transmission electron microscopy. Single particle averaging revealed additional domains not observed previously. Secretin complexes of N. gonorrhoeae showed a double ring structure with a 14-15-fold symmetry in the central ring, and a 14-fold symmetry of the peripheral ring with 7 spikes protruding. In secretin complexes of N. meningitidis, the spikes were absent and the peripheral ring was partly or completely lacking. When present, it had a 19-fold symmetry. The structures of the complexes in several pil mutants were determined. Structures obtained from the pilC1/C2 adhesin and the pilW minor pilin deletion strains were similar to wild-type, whereas deletion of the homologue of N. meningitidis PilW resulted in the absence of secretin structures. Remarkably, the pilE pilin subunit and pilP lipoprotein deletion mutants showed a change in the symmetry of the peripheral ring from 14 to 19 and loss of spikes. The pilF ATPase mutant also lost the spikes, but maintained 14-fold symmetry. These results show that secretin complexes contain previously unidentified large and flexible extra domains with a probable role in stabilization or assembly of type IV pili

    Assembly Factor Omp85 Recognizes Its Outer Membrane Protein Substrates by a Species-Specific C-Terminal Motif

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    Integral β-barrel proteins are found in the outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts. The assembly of these proteins requires a proteinaceous apparatus of which Omp85 is an evolutionary conserved central component. To study its molecular mechanism, we have produced Omp85 from Escherichia coli in inclusion bodies and refolded it in vitro. The interaction of Omp85 with its substrate proteins was studied in lipid-bilayer experiments, where it formed channels. The properties of these channels were affected upon addition of unfolded outer-membrane proteins (OMPs) or synthetic peptides corresponding to their C-terminal signature sequences. The interaction exhibited species specificity, explaining the inefficient assembly of OMPs from Neisseria in E. coli. Accordingly, the in vivo assembly of the neisserial porin PorA into the E. coli outer membrane was accomplished after adapting its signature sequence. These results demonstrate that the Omp85 assembly machinery recognizes OMPs by virtue of their C-terminal signature sequence

    Strategies in Rapid Genetic Diagnostics of Critically Ill Children:Experiences From a Dutch University Hospital

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    Background: Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations. Methods: We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs). Results: Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%). Conclusion: We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel

    Mountain building in Taiwan: A thermokinematic model

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    The Taiwan mountain belt is classically viewed as a case example of a critical wedge growing essentially by frontal accretion and therefore submitted to distributed shortening. However, a number of observations call for a significant contribution of underplating to the growth of the orogenic wedge. We propose here a new thermokinematic model of the Taiwan mountain belt reconciling existing kinematic, thermometric and thermochronological constraints. In this model, shortening across the orogen is absorbed by slip on the most frontal faults of the foothills. Crustal thickening and exhumation are sustained by underplating beneath the easternmost portion of the wedge (Tananao Complex, TC), where the uplift rate is estimated to ~6.3 mm a^(−1), and beneath the westernmost internal region of the orogen (Hsueshan Range units, HR), where the uplift rate is estimated to ~4.2 mm a^(−1). Our model suggests that the TC units experienced a synchronous evolution along strike despite the southward propagation of the collision. It also indicates that they have reached a steady state in terms of cooling ages but not in terms of peak metamorphic temperatures. Exhumation of the HR units increases northward but has not yet reached an exhumational steady state. Presently, frontal accretion accounts for less than ~10% of the incoming flux of material into the orogen, although there is indication that it was contributing substantially more (~80%) before 4 Ma. The incoming flux of material accreted beneath the TC significantly increased 1.5 Ma ago. Our results also suggest that the flux of material accreted to the orogen corresponds to the top ~7 km of the upper crust of the underthrust Chinese margin. This indicates that a significant amount (~76%) of the underthrust material has been subducted into the mantle, probably because of the increase in density associated with metamorphism. We also show that the density distribution resulting from metamorphism within the orogenic wedge explains well the topography and the gravity field. By combining available geological data on the thermal and kinematic evolution of the wedge, our study sheds new light onto mountain building processes in Taiwan and allows for reappraising the initial structural architecture of the passive margin

    An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential

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    Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract
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