986 research outputs found
Biochemical Characterization of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: Meso-2,6-diaminopimelate ligase (MurE) from Verrucomicrobium spinosum DSM 4136T
No full textVerrucomicrobium spinosum is a Gram-negative bacterium that is related to bacteria from the genus Chlamydia. The bacterium is pathogenic towards Drosophila melanogaster and Caenorhabditis elegans, using a type III secretion system to facilitate pathogenicity. V. spinosum employs the recently discovered l,l-diaminopimelate aminotransferase biosynthetic pathway to generate the bacterial cell wall and protein precursors diaminopimelate and lysine. A survey of the V. spinosum genome provides evidence that the bacterium should be able to synthesize peptidoglycan de novo, since all of the necessary genes are present. The enzyme UDP-N-acetylmuramoyl-l-alanyl-d-glutamate: meso-2,6-diaminopimelate ligase (MurE) (E.C. 6.3.2.15) catalyzes a reaction in the cytoplasmic step of peptidoglycan biosynthesis by adding the third amino acid residue to the peptide stem. The murE ortholog from V. spinosum (murE Vs) was cloned and was shown to possess UDP-MurNAc-l-Ala-d-Glu:meso-2,6-diaminopimelate ligase activity in vivo using functional complementation. In vitro analysis using the purified recombinant enzyme demonstrated that MurEVs has a pH optimum of 9.6 and a magnesium optimum of 30 mM. meso-Diaminopimelate was the preferred substrate with a K m of 17 µM, when compared to other substrates that are structurally related. Sequence alignment and structural analysis using homology modeling suggest that key residues that make up the active site of the enzyme are conserved in MurEVs. Our kinetic analysis and structural model of MurEVs is consistent with other MurE enzymes from Gram-negative bacteria that have been characterized. To verify that V. spinosum incorporates diaminopimelate into its cell wall, we purified peptidoglycan from a V. spinosum culture; analysis revealed the presence of diaminopimelate, consistent with that of a bona fide peptidoglycan from Gram-negative bacteria
Population matched (pm) germline allelic variants of immunoglobulin (IG) loci: Relevance in infectious diseases and vaccination studies in human populations
No full textImmunoglobulin (IG) loci harbor inter-individual allelic variants in many different germline IG variable, diversity and joining genes of the IG heavy (IGH), kappa (IGK) and lambda (IGL) loci, which together form the genetic basis of the highly diverse antigen-specific B-cell receptors. These allelic variants can be shared between or be specific to human populations. The current immunogenetics resources gather the germline alleles, however, lack the population specificity of the alleles which poses limitations for disease-association studies related to immune responses in different human populations. Therefore, we systematically identified germline alleles from 26 different human populations around the world, profiled by “1000 Genomes” data. We identified 409 IGHV, 179 IGKV, and 199 IGLV germline alleles supported by at least seven haplotypes. The diversity of germline alleles is the highest in Africans. Remarkably, the variants in the identified novel alleles show strikingly conserved patterns, the same as found in other IG databases, suggesting over-time evolutionary selection processes. We could relate the genetic variants to population-specific immune responses, e.g. IGHV1-69 for flu in Africans. The population matched IG (pmIG) resource will enhance our understanding of the SHM-related B-cell receptor selection processes in (infectious) diseases and vaccination within and between different human populations.Pattern Recognition and Bioinformatic
Plattformen gewerkschaftlicher Europapolitik: IG Metall und IG CPK und der Prozess der europäischen Integration in den 1960er und 1970er Jahren
No full textThe article focuses on influences and reactions of the German industrial unions IG Metall and IG CKP to the European integration process during the 1960s and 1970s. Within this context the author describes levels and instruments of engagement and points out the different views, problems and starting points of two leading industrial unions during the foundation of the EEC and ETUC. Therein, the article highlights different strategies of the trade unions due to their political and economic interests on the one hand and possibilities, given to them by European representative structures, on the other hand. In addition, the article also sketches their engagement at the level of sectoral trade union organisation
Ig od leta 1952 do ustanovitve Občine Ljubljana Vič-Rudnik
No full textThe article discusses the development of the village of Ig between 1952 and 1961. The relatively short period brought about quite a number of administrative changes, from Ig being an independent municipality to its incorporation into the Municipality Ljubljana Vič–Rudnik. The author first presents the holders of local authority and the local economic development. Ig developed slowly, and despite the aspirations to industrialisation, the inhabitants still largely depended on agriculture. The only major enterprise was the metals industry company (Kovinska industrija Ig), whereas crafts and trade were poorly developed. Modest financial funds resulted in the sluggish development of infrastructure and the biggest desire among the local population was to modernise the water main. Lastly, the article also describes the development of education and healthcare, as well as the local everyday life. The latter remained modest until at least the mid-1950s. Major changes in lifestyle and living standard only occurred at the turn of the decade.Prispevek obravnava razvoj vasi Ig med letoma 1952 in 1961. Razmeroma kratko obdobje je prineslo kar nekaj upravnih sprememb, od samostojne občine do vključitve v občino Ljubljana Vič-Rudnik. Najprej so predstavljeni nosilci lokalne oblasti in gospodarski razvoj kraja. Ig se je razvijal počasi, kljub željam po industrializaciji so bili prebivalci še vedno v veliki meri odvisni od kmetijstva. Večje podjetje je bilo Kovinska industrija Ig, obrt in trgovina sta bili slabše razviti. Skromnim finančnim sredstvom je sledil tudi počasen razvoj infrastrukture, največja želja je bila modernizacija vodovoda. Na koncu so opisani še razvoj šolstva in zdravstvene oskrbe ter vsakdanje življenje prebivalcev. Slednje je ostajalo skromno vsaj do sredine petdesetih let, večje spremembe v načinu življenja in standardu so prišle ob prelomu desetletja
Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains
No full textMyotilin is a component of the sarcomere where it plays an important role in organisation and maintenance of Z-disk integrity. This involves direct binding to F-actin and filamin C, a function mediated by its Ig domain pair. While the structures of these two individual domains are known, information about their relative orientation and flexibility remains limited. We set on to characterise the Ig domain pair of myotilin with emphasis on its molecular structure, dynamics and phylogeny. First, sequence conservation analysis of myotilin shed light on the molecular basis of myotilinopathies and revealed several motifs in Ig domains found also in I-band proteins. In particular, a highly conserved Glu344 mapping to Ig domain linker, was identified as a critical component of the inter-domain hinge mechanism. Next, SAXS and molecular dynamics revealed that Ig domain pair exists as a multi-conformation species with dynamic exchange between extended and compact orientations. Mutation of AKE motif to AAA further confirmed its impact on inter-domain flexibility. We hypothesise that the conformational plasticity of the Ig domain pair in its unbound form is part of the binding partner recognition mechanism.© The Author(s) 201
Reconstruction of Directional Spectra of Infragravity Waves
No full textUnderstanding directional spectra of infragravity (IG) waves composed of free and bound components is required due to their impacts on various coastal processes (e.g., coastal inundation and morphological change). However, conventional reconstruction methods of directional spectra relying on linear wave theory are not applicable to IG waves in intermediate water depths (20–30 m) due to the presence of bound waves. Herein, a novel method is proposed to reconstruct directional spectra of IG waves in intermediate depth based on weakly nonlinear wave theory. This method corrects cross-spectra among observed wave signals by taking account of the nonlinearity of bound waves in order to reconstruct directional spectra of free IG waves. Numerical experiments using synthetic data representing various directional distributions show that the proposed method reconstructs free IG wave directional spectra more accurately than the conventional method. The method is subsequently applied to observations of severe sea-states at two field sites. At these sites, free IG waves are not isotropic and have clear peak directions. Numerical modeling of the wave fields shows that these peak directions correspond to the reflection of IG waves from the shore and/or coastal structures. Additionally, the validity of the underlying weakly nonlinear wave theory of the present method is assessed by a newly proposed method employing bispectral analysis. The bound wave response generally agrees with the theory at the field sites but deviates slightly for energetic sea states. The applicability of the present method on a sloping bottom is further discussed by an analytical solution.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Environmental Fluid Mechanic
North sea infragravity wave observations
No full textCoastal safety assessments with wave-resolving storm impact models require a proper offshore description for the incoming infragravity (IG) waves. This boundary condition is generally obtained by assuming a local equilibrium between the directionally-spread incident sea-swell wave forcing and the bound IG waves. The contribution of the free incident IG waves is thus ignored. Here, in-situ observations of IG waves with wave periods between 100 s and 200 s at three measurement stations in the North Sea in water depths of O(30) m are analyzed to explore the potential contribution of the free and bound IG waves to the total IG wave height for the period from 2010 to 2018. The bound IG wave height is computed with the equilibrium theory of Hasselmann using the measured frequency-directional sea-swell spectra as input. The largest IG waves are observed in the open sea with a maximum significant IG wave height of O(0.3) m at 32 m water depth during storm Xaver (December 2013) with a concurrent significant sea-swell wave height in excess of 9 m. Along the northern part of the Dutch coast, this maximum has reduced to O(0.2) m at a water depth of 28 m with a significant sea-swell wave height of 7 m and to O(0.1) m at the most southern location at a water depth of 34 m with a significant sea-swell wave height of 5 m. These appreciable IG wave heights in O(30) m water depth represent a lower bound for the expected maximum IG wave heights given the fact that in the present analysis only a fraction of the full IG frequency range is considered. Comparisons with the predicted bound IG waves show that these can contribute substantially to the observed total IG wave height during storm conditions. The ratio between the predicted bound-and observed total IG variance ranges from 10% to 100% depending on the location of the observations and the timing during the storm. The ratio is typically high at the peak of the storm and is lower at both the onset and waning of the storm. There is significant spatial variability in this ratio between the stations. It is shown that differences in the directional spreading can play a significant role in this. Furthermore, the observed variability along the Dutch coast, with a substantially decreased contribution of the bound IG waves in the south compared to the northern part of the Dutch coast, are shown to be partly related to changes in the mean sea-swell wave period. For the southern part of the Dutch coast this corresponds to an increased difference with the typically assumed equilibrium boundary condition although it is not clear how much of the free IG-energy is onshore directed barring more sophisticated observations and/or modeling.Environmental Fluid MechanicsCoastal Engineerin
Cross-shore transformation of bound and free infragravity waves off the Dutch coast
No full textInfragravity (IG) waves are key drivers for coastal erosion and thus need to be properly included in process-based modelling of coastal hazards. Uncertainties remain regarding the offshore boundary conditions for these long waves. Typically, only bound IG waves are included at the boundary, which means that the possible contribution of free IG waves, such as those radiated from distant coastlines, is neglected. Recent studies however suggest that incoming free IG waves could be significant, particularly in semi-enclosed basins such as the North Sea where they could contribute to coastal hazards (e.g., Reniers et al., 2021, Rijnsdorp et al. 2021). The objective of this work is to improve the understanding of the incoming IG wave field along the Dutch coast. We will quantify how bound and free IG waves develop in intermediate water depths and assess in which conditions (onshore directed) free IG waves become significant.Environmental Fluid MechanicsCoastal Engineerin
Field Observations of Infragravity Waves off the Dutch Coast
No full textInfragravity (IG) waves (0.005-0.04 Hz) are surface waves that can dominate the nearshore hydrodynamics and can impact various coastal processes (e.g., run-up, overwash). A proper offshore description of incident IG waves is required for storm impact models, which generally assume a local equilibrium between sea-swell (SS) waves (0.04-0.33 Hz) and the resultant nonlinearly excited bound IG waves. The contribution of free incident IG waves and the directional propertiesof the IG wave field are neglected, though they play a critical role in IG wave variations. Various research focuses on IG wave dynamics in shallow waters, but a detailed understanding of IG wave variability in intermediate water depth is lacking. Furthermore, the directional spectra of bound and free IG waves in the field are usually unavailable since bound IG waves do not follow linear dispersion relations, which is assumed by commonly applied directional spectra reconstruction methods.In-situ observation data (surface elevation, pressure, and velocity) of IG waves from November 2021 to April 2022 at three cross-shore locations in intermediate water depth (∼ 6 − 14 m) off the Dutch coast are analyzed to study generation, propagation, and directional properties of IG waves. The bispectral technique is applied to quantify the contribution of bound IG waves to the total IG wave field. A newly developed method is validated and used on the offshore (∼ 14 m) data to reconstruct directional spectra of bound and free IG waves separately during storms.The results show that IG wave heights are best predicted (correlation coefficient R² up to 0.94) with an offshore forcing parameter that includes peak period HssTp2 , which indicates SS wave energy flux. The growth rate of IG waves is in between the shallow water equilibrium solution (for bound waves) and Green’s Law (for free waves), indicating the total IG wave field consists of bound and free components. The relative contribution of bound IG energy (up to 76%) is correlated to SS wave energy, whereas it decreases dramatically during intense storms when SS waves break. The bound IG waves that are assumed to follow the weakly nonlinear wave theory, have a similar peak direction and broader directional spreading to SS waves. In contrast, the directional spectra of free IG waves are nearly isotropic during calm conditions, but may have diverse peaks during storms, which incident IG waves from remote sources and edge waves caninfluence. A better understanding of the complex pattern of free IG waves requires more detailed observations and/ or modeling.Geo-Engineerin
Praxisbericht: Erfolgsstrategien für Geschlechterpolitik in einer männlich dominierten Organisation am Beispiel der IG Metall
No full textIndustriegewerkschaften und allen voran die IG Metall galten und gelten auch heute noch als der Prototyp einer spezifisch männlich dominierten Organisation. Der Beitrag beschreibt die genderpolitischen Entwicklungslinien innerhalb der IG Metall, die von der absoluten Unterrepräsentanz von Frauen hin zu einem für Industriegewerkschaften weltweit bisher nicht gekannten Frauenanteil von 30 Prozent bei den Gewerkschaftssekretärinnen und -sekretären sowie einem stetig steigenden Anteil von Frauen bei den hauptamtlichen Führungspositionen geführt haben. Die Autorin analysiert die Erfolgsfaktoren und hier insbesondere die Verbindung des Gender- und Diversitätsthemas mit der strategischen Neuausrichtung und damit einhergehenden Organisationsentwicklungs- und Modernisierungsprozessen der IG Metall, um sich angesichts des gesellschaftlichen und industriellen Strukturwandels gestärkt aufzustellen. Der Beitrag schließt mit einem Ausblick auf alte und neue Herausforderungen.Industrial trade unions, above all IGM, have long been regarded as protypical male-dominated organisations. This report describes IGM gender-political developments that have led from a totally under-represented state for women to a 30 percent women share of full-time union officials at IGM, as well as to a steadily increasing share of the leading positions at IGM. The author, who has had years of active experience in IGM`s gender policy, analyses the success factors, in particular the connection of gender and diversity themes with IGM`s strategic reorientation, its organisational development and modernisation processes (undertaken to meet the social and industrial requirements of structural change). The article concludes with an outlook on old and new challenges
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