1,168 research outputs found
Tuning of influenza A virus neuraminidase activity
No full textInfluenza A viruses (IAVs) are zoonotic pathogens that constantly circulate in a wide variety of species, including birds, pigs and humans. In humans, IAVs cause seasonal epidemics and occasional influenza pandemics. Annual epidemics caused by seasonal IAVs usually lead to millions of human infections, posing great threats to public health and cause large economic burdens. Influenza pandemic occurs when animal viruses managed to cross the host species barrier and became transmissible among humans. IAV pandemics have occurred four times in the 100 years, causing millions of deaths and global devastating effects. IAVs are enveloped, segmented negative-strand RNA viruses belonging to the Orthomyxoviridae family. There are two main important glycoproteins in the IAV virus membrane, hemagglutinin (HA) and neuraminidase (NA), both of which recognize sialic acids (SIAs). The HA protein is responsible for virus-cell attachment via binding to sialylated receptors at the cell surface. The NA protein is the receptor-destroying enzyme and responsible for removing SIA from host glycoproteins as well as glycolipids, thereby allowing release of progeny virions from cells and decoy receptors and preventing virus self-aggregation. A functional balance between the HA and NA proteins is of importance for maintaining optimal virus replication as well as transmission across different host speciesADDIN RW.CITE{{36 Xu,R. 2012; 37 Yen,H.L. 2011; 38 de Wit,E. 2010}}. While HA receptor-binding avidity and specificity have been studied in detail, much less is known about the molecular determinants that mediate (changes in) the specificity and activity of IAV NA proteins. The overall aim of this thesis was to unravel to what extent and how IAVs modulate the activity of their NA proteins during virus evolution. To this end, NA functionality, mainly enzymatic activity has been extensively investigated by using an optimized recombinant soluble protein approach. By doing so, we not only identified an optimal recombinant soluble NA expression approach, but also identified residues that affected NA folding and/or enzymatic activity. With the established recombinant soluble approach, we further found an important role of the 2nd SIA-binding site in NA enzymatic activity. Mutation of the 2nd SIA binding site provides viruses with an additional mechanism to manipulate the enzymatic activity of their NA proteins without having to mutate their active site residues directly. The studies presented in this thesis also highlight some complexities of HA/NA balance during virus evolution. Different NA phenotypic properties of H1N1pdm09 virus were found to be intertwined, with several NA substitutions affecting more than one phenotypic characteristic. The phenotypic changes of NA are probably also linked to the properties of the HA protein and corresponding HA/NA balance, which makes evolution of HA and NA more difficult to understand
Guilds in the transition to modernity: The cases of Germany, United Kingdom, and the Netherlands
No full textOne important aspect of the transition to modernity is the survival of elements of the Old Regime beyond the French Revolution. It has been claimed that this can explain why in the late nineteenth and early twentieth centuries some Western countries adopted national corporatist structures while others transformed into liberal market economies. One of those elements is the persistence or absence of guild traditions. This is usually analyzed in a national context. This article aims to contribute to the debate by investigating the development of separate trades in Germany, the United Kingdom, and The Netherlands throughout the nineteenth century. We distinguish six scenarios of what might have happened to crafts and investigate how the prevalence of each of these scenarios in the three countries had an impact on the emerging national political economies. By focusing on trades, rather than on the national political economy, our analysis demonstrates that in each country the formation of national political economies and citizenship rights was not the result of a national pattern of guild survival. Rather, the pattern that emerged by the end of the nineteenth century was determined by the balance between old and new industries, and that between national and regional or local government
Peroxisomen en de adrenerge controle van wit vetweefsel en skeletspier
No full textPeroxisomen zijn subcellulaire organellen die een belangrijke rol spelen in het lipidenmetabolisme. Hun essentiële functie wordt benadrukt door het bestaan van ziekten veroorzaakt door een peroxisomaal biogenese defe ct of door mutaties in een peroxisomaal enzym. Ze zijn voornamelijk geke nmerkt door afwijkingen in het centraal zenuwstelsel als ook ter hoogte van de lever. Tot op de dag van vandaag is echter weinig gerapporteerd o ver de functie van peroxisomen in vetweefsel. Het doel van deze thesis w as na te gaan of peroxisomen een essentiële rol vervullen bij de ontwikk eling van adipocyten, en of ze vereist zijn voor een normaal functionere n van zowel wit als bruin vetweefsel. De rol van peroxisomen in de differentiatie van preadipocyten tot adipoc yten, werd onderzocht door in vitro adipogenese van wild type en P ex5 deficiënte muriene embryonale fibroblasten. Gedurende het hele pr oces was de genexpressie van differentiatiemerkers PPARγ en aP2< /> niet verschillend tussen de twee groepen. Ook lipidenstapeling in de terminaal gedifferentieerde adipocyt was vergelijkbaar tussen wild type en Pex5 deficiënte fibroblasten. Hieruit konden we besluiten dat pero xisomen niet noodzakelijk zijn voor adipogenese. Om het functioneel belang van peroxisomen in vetweefsel in vivo na te gaan, werd een muismodel met selectieve eliminatie van peroxisomen in a dipocyten aangemaakt, door Pex5FL/FL muizen in te kruisen met aP2-Cre muizen (in eerste instantie ter beschikking gesteld door B. Kahn, Bo ston, USA). Deze muizenlijn was echter niet bruikbaar gezien de geringe en variabele eliminatie van peroxisomen in het vetweefsel. Daarom werd d e kweek herbegonnen met een andere aP2-Cre muizenlijn (ter beschikkin g gesteld door R. Evans, San Diego, USA). Dit muismodel vertoonde een na genoeg volledige recombinatie van het Pex5 gen in wit en in bruin vet weefsel. Er werd geen recombinatie waargenomen in meerdere andere weefse ls, zoals lever, hart, colon, spier. Onverwacht echter bleken import inc ompetente peroxisomen ook aanwezig te zijn in de hersenen en ganglia van het perifere zenuwstelsel. In vergelijking met controle muizen, hadden aP2-Pex5-/- muizen sig nificant meer wit vetweefsel, wat correleerde met verhoogde plasma waard en van leptin. Onder gevaste omstandigheden was de lipolytische capacite it gedaald. Dit ging gepaard met gedaalde genexpressie van ß3-adren erge receptoren. De hoeveelheid bruin vetweefsel daarentegen was niet ve rschillend. Naast de veranderingen in wit vetweefsel waren ook systemisc he abnormaliteiten aanwezig. Lichaamsgewicht van de aP2-Pex5-/- mu izen was lager en plasma waarden van insuline waren verhoogd. Opmerkelij k was dat ondanks de aanwezigheid van normale peroxisomen in de dwarsges treepte spier, de opname van glucose ter hoogte van de spier sterk gedaa ld was. Dit hield verband met verlaagde Glut4 genexpressie en vermind erde insuline gevoeligheid. Als gevolg hiervan was de loopcapaciteit van de aP2-Pex5-/- muizen sterk gedaald en waren ze niet in staat hun lic haamstemperatuur te handhaven bij acute blootstelling aan kou in gevaste toestand. Onder deze laatste omstandigheden, bleek de concentratie nora drenaline in plasma gehalveerd te zijn, terwijl de concentratie adrenali ne niet betrouwbaar kon gemeten worden. Aangezien muizen met selectieve eliminatie van peroxisomen in de hersenen deze metabole afwijkingen niet vertoonden, lijkt de verlaagde adrenerge respons niet afkomstig te zijn vanuit de hersenen. Het sluitende bewijs voor een verlaagde adrenerge respons in wit vetweef sel en spier van aP2-Pex5-/- muizen werd geleverd door behandeling met de niet-selectieve ß-agonist isoproterenol. Deze therapie resu lteerde in normalisatie van het aantal ß2-adrenerge receptoren e n Glut4 transporters in de dwarsgestreepte spier, in een verbeterde moto rische activiteit en in de mogelijkheid om te overleven bij acute bloots telling aan kou onder gevaste omstandigheden. Ook het aantal ß3- ad renerge receptoren in WAT normaliseerde. Wij kunnen besluiten dat de afwezigheid van peroxisomen ten gevolge van aP2-Cre expressie aanleiding geeft tot verminderde adrenerge respo ns in wit vetweefsel en spier van aP2-Pex5-/- muizen. Of deze dali ng te wijten is aan afwezigheid van peroxisomen in de perifere ganglia e n/of afwezigheid van peroxisomen in vetweefsel moet verder worden onderz ocht. Andere onbeantwoorde vragen zijn: 1) hoe kan de afwezigheid van pe roxisomen hieraan gelinkt worden, en 2) is een gedaalde adrenerge respon s ook aanwezig in andere organen.status: Publishe
Structural requirements for O-glycosylation of the mouse hepatitis virus membrane protein
No full textThe mouse hepatitis virus (MHV) membrane (M) protein contains only O-linked oligosaccharides. We have used this protein as a model to study the structural requirements for O-glycosylation. We show that MHV M is modified by the addition of a single oligosaccharide side chain at the cluster of 4 hydroxylamino acids present at its extreme amino terminus and identified Thr at position 5 as the functional acceptor site. The hydroxylamino acid cluster, which is quite conserved among O-glycosylated coronavirus M proteins, is not in itself sufficient for O-glycosylation. Downstream amino acids are required to introduce a functional O-glycosylation site into a foreign protein. In a mutagenic analysis O-glycosylation was found to be sensitive to some particular changes but no unique sequence motif for O-glycosylation could be identified. Expression of mutant M proteins in cells revealed that substitution of any 1 residue was tolerated, conceivably due to the occurrence of multiple UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc transferases). Indeed, MHV M served as a substrate for GalNac-T1, -T2, and -T3, as was demonstrated using an in situ glycosylation assay based on the co-expression of endoplasmic reticulum-retained forms of the GalNAc transferases with endoplasmic reticulum-resident MHV M mutants. The GalNAc transferases were found to have largely overlapping, but distinct substrate specificities. The requirement for a threonine as acceptor rather than a serine residue and the requirement for a proline residue three positions downstream of the acceptor site were found to be distinctive features
Failures and Mistakes: Images of collaboration in postwar Dutch society
No full textIn Onderdrukking en verzet (Repression and Resistance), the first comprehensive history of World War II in the Netherlands, Henk van Randwijk discussed the distinction between goed and fout, right and wrong. According to van Randwijk, who was editor of the underground newspaper Vrij Nederland, this was a distinction used extensively during the war to differentiate between those “one could trust and with whom one could share the secrets of underground and open resistance” and those “about whom one could not say this with 100 percent certainty.” While acknowledging that it was a very crude distinction of limited use, Van Randwijk claimed it was necessary in times when “even minimal knowledge in the hands of the wrong people might have had the worst consequences.” However, applying it after the war had ended would lead to “grave injustice. … to wit, when the danger had passed, there was room for more subtle distinctions. From then on, it was no longer a matter of self-protection but of a sense of justice.” Quoting the last minister of the interior of the Dutch government-in-exile in London, Jaap Burger, Van Randwijk stressed the difference between fout, as a matter of ideological conviction, and fouten begaan, making mistakes, due to a flawed judgment of the situation. The latter was very often the case, according to van Randwijk, since mentally the Netherlands was completely unprepared for the war. Although the nature of the Nazi regime was clear to anyone prepared to look across the eastern border, in the first years of the occupation many had hoped to negotiate a fair deal with the Germans, thus preserving at least part of the nation’s pride and independence. Only a few understood immediately the true nature of Nazi Germany and acted accordingly
Very High Energy Gamma-Rays from Binary Systems
No full textThis thesis presents a study of the very high energy (VHE) gamma-ray emission from X-ray binary systems using the H.E.S.S. imaging atmospheric Cherenkov array.
The historical background and basic principles of ground-based gamma-ray astronomy are briefly reviewed and an overview of the design and capabilities of the H.E.S.S. telescope system is presented. The broadband observational properties of X-ray binary systems and their relevance in a broader astrophysical context is also discussed.
A review of the radiative emission mechanisms which relate to VHE gamma-ray emission in X-ray binaries is presented, with emphasis given to the leptonic emission processes of synchrotron radiation and inverse-Compton scattering. Intrinsic absorption processes which act to attenuate the emitted flux of VHE gamma-rays are also discussed. Three computer models are introduced which simulate aspects of the gamma-ray emission and absorption in X-ray binary systems.
A detailed analysis of the VHE gamma-ray emission from the X-ray binary LS 5039 is presented and the relevant procedures for data selection, gamma-hadron separation and background estimation are discussed in some detail. Methods for the determination of detection significance and the calculation of gamma-ray fluxes are also reviewed and results are derived which apply specifically to LS 5039. A detailed temporal analysis of the gamma-ray signal from LS 5039 is presented, applying tests for secular, excess and periodic variability. Strong evidence is found for modulation of the observed gamma-ray flux on the orbital period of ~3.9 days. Following a brief discussion of the procedures required for spectral analysis of VHE gamma-ray data, results are presented for LS 5039 which reveal evidence for spectral variability which is correlated with the observed gamma-ray flux and therefore, the orbital phase of the binary system. The spectral and temporal characteristics of LS 5039 are then compared with the predictions of theoretical models in an attempt to explain the observed behaviour.
Contemporaneous X-ray and VHE gamma-ray observations of three galactic microquasars using the Rossi X-ray Timing Explorer and H.E.S.S. are presented. Although no gamma-ray detections are reported, the observations permit the derivation of upper limits to the VHE gamma-ray flux which correspond to episodes of known X-ray behaviour. The X-ray characteristics of each target are compared with pre-existing observational data to infer the presence or otherwise of relativistic outflows at the H.E.S.S. observation epochs. The implications of the gamma-ray non-detections are then discussed in the context of these inferred system properties.
The results of a survey of the VHE gamma-ray emission associated with the positions of 125 known X-ray binaries are presented. Although no conclusive detections were obtained, tentative indications were found for a population of faint, spectrally hard gamma-ray sources associated with high-mass X-ray binary systems. The inferred characteristics of the indicated population show broad agreement with the measured properties of known gamma-ray-emitting X-ray binary systems like LS 5039
Caracterização biométrica de frutos e sementes e potencial de emergência de plântulas de Leucaena leucocephala (Lam.) de Wit., espécie invasora
No full textLeucaena leucocephala (Lam.) de Wit., introduzida no Brasil para produzir madeira e forragem
e recuperar áreas degradadas, se tornou uma invasora agressiva que impacta ecossistemas e
dificulta a regeneração da flora nativa. Espécies invasoras apresentam grande produção de
sementes pequenas e de fácil dispersão, crescimento rápido, alta taxa de germinação e alta
adaptabilidade a ambientes adversos. A posição e a profundidade da semente no solo podem
favorecer a emergência e melhorar a uniformidade das plântulas. Diante disso, o objetivo com
esse estudo foi caracterizar biometricamente frutos e sementes, e investigar o potencial de
emergência de plântulas de L. leucocephala em diferentes posições e profundidades de
semeadura. Em uma amostra de 200 frutos e sementes, determinou-se comprimento (CFR, cm),
largura (LFR, cm), espessura (EFR, cm) e peso (PFR, g) dos frutos e número de sementes fruto1
(NSFR). Nas sementes, mensurou-se comprimento (CS, cm), largura (LS, cm) e espessura
(ES, cm) de sementes e peso de mil sementes (PMS, g). O experimento foi conduzido em casa
de vegetação, na Universidade Estadual da Paraíba, em Catolé do Rocha, PB. O delineamento
foi inteiramente casualizado, em esquema fatorial 3 x 6, com 4 repetições de 25 sementes com
o hilo para baixo (HB), para o lado (HL) e para cima (HC), nas profundidades de 05; 1,0; 1,5;
2,0; 2,5 e 3,0. Avaliou-se primeira contagem de emergência (PCE, %), percentual de
emergência (E, %), índice de velocidade de emergência (IVE), comprimento de raiz (CR, cm)
e parte aérea (CPA, cm), relação raiz/parte aérea (RR/PA), massa seca de raízes (MSR, g), de
parte aérea (MSPA, g) e total (MST, g) das plântulas. Não houve ajuste aos modelos
polinomiais testados para a posição HB e HL. Na posição HC, verificou-se maior E (82%) na
maior profundidade de semeadura (3,0 cm). Não houve interação significativa entre posição e
profundidade de semeadura para PCE, IVE, CR, CPA, MSR, MSPA, RR/PA e MST. Além
disso, não houve ajuste aos modelos polinomiais quadrático e linear para a MSPA e MST de
plântulas de L. leucocephala. Os maiores valores para a PCE (38%), IVE (4,4), CR (9,6 cm),
MSR (0,58 g) e RR/PA (0,40) foram obtidos na profundidade de 0,5 cm. De forma inversa, o
maior CPA (6,7 cm) foi observado na profundidade de 3,0 cm. L. leucocephala produz frutos
com uma grande quantidade de sementes pequenas e leves, que têm sua emergência favorecida
pela semeadura em menores profundidades. Essas características demonstram o potencial
competitivo dessa invasora, em explorar ambientes com recursos limitados, típicos do
semiárido nordestino
The effect of a portion size intervention on French fries consumption, plate waste, satiety and compensatory caloric intake: an on-campus restaurant experiment
No full textAbstract Background One of the driving factors of dietary overconsumption throughout the last decennia is the increase of food portion sizes. Larger portions induce higher daily energy intake, so reducing portion size may reduce intake of excess calories. However, real-life studies about the effects of portion size reduction are lacking. Therefore, this study examined the effect of a French fries portion size reduction on French fries consumption, French fries plate waste, satiety and caloric intake during the subsequent afternoon among university students and employees in a Belgian on-campus restaurant setting. Moreover, this study evaluated consumers’ perception about the portion size reduction. Methods The study took place over a two-time (i.e. baseline and intervention week) 4-day period (Tuesday–Friday) in the on-campus restaurant where ±1200 meals are served every day. French fries’ portions were reduced by 20% by replacing the usual porcelain bowl served during the baseline week (±200 g) with smaller volume paper bags during the intervention week (±159 g) in a pre-post real-life experiment. French fries consumption and plate waste were measured in 2056 consumers at baseline and 2175 consumers at intervention. Additionally, interviews were conducted directly after lunch and again between 4 and 6 p.m. on the same day to assess satiety and caloric intake at pre and post in a small subsample of both French fries consumers (n = 19) and non-French fries consumers (n = 14). Post-intervention, the same subsample was interviewed about their perception of the portion size reduction (n = 28). Results Total French fries intake decreased by 9.1%, and total plate waste decreased by 66.4%. No differences were found in satiety or caloric intake between baseline and intervention week among the French fries’ consumers. The majority (n = 24, 86%) of French fries consumers noticed the reduction in portion size during the intervention. Although most participants (n = 19, 68%) perceived the reduced portion size as sufficient, only a minority of participants (n = 9, 32%) indicated post-intervention that they would agree with a permanent implementation. Conclusions Reducing portion size may lead to reduced caloric intake, without changing perceived levels of satiety
A systematic scoping review on contextual factors associated with communicative participation among children with developmental language disorder
No full textBackgroundVariations in communicative participation of children with developmental language disorder (DLD) cannot be wholly explained by their language difficulties alone and may be influenced by contextual factors. Contextual factors may support or hinder communicative participation in children, which makes their identification clinically relevant.AimsTo investigate which contextual (environmental and personal) factors in early childhood are protective, risk or neutral factors for communicative participation among school-aged children with DLD, and to identify possible gaps in knowledge about this subject.Methods & ProceduresA scoping review was conducted based on a systematic search of studies published from January 2007 to March 2022 in Pubmed, Embase (without MEDLINE), CINAHL and PsycINFO. In total, 8802 studies were reviewed using predefined eligibility criteria, of which 32 studies were included for data extraction and critically appraised using the Critical Appraisal Skills Programme (2021) tools.Main ContributionThe methodological quality of included studies was adequate to strong. Personal protective factors identified are being a preschool girl, reaching school age and being prosocial, while personal risk factors are becoming a teenager or adolescent, having low socio-cognitive skills and experiencing comorbid mobility impairment or behavioural problems. Gender after the preschool years and non-verbal abilities were not found to be of influence, and the role of socio-emotional skills is inconclusive. Receiving therapy is an environmental protective factor, while the association between socio-economical family characteristics with communicative participation is inconclusive.Conclusions & ImplicationsLimited research has been conducted on which risk and protective factors present in early childhood are associated with later communicative participation of children with DLD. The influence of co-occurring health conditions, social background variables, individual psychological assets, interpersonal relationships and attitudes of other people represent knowledge gaps. In addition, knowledge about the comparative effectiveness of different types of interventions and service delivery models, and the impact of administrative control, organizational mechanisms and standards established by governments on children's communicative participation is lacking. More longitudinal research is needed focusing on the identification of relevant personal and environmental factors and the interactions between them in relation to communicative participation outcomes
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