2,317 research outputs found
Comparison of the Immune Responses Induced by Chimeric Alphavirus-Vectored and Formalin-Inactivated Alum-Precipitated Measles Vaccines in Mice
A variety of vaccine platforms are under study for development of new vaccines for measles. Problems with past measles vaccines are incompletely understood and underscore the need to understand the types of immune responses induced by different types of vaccines. Detailed immune response evaluation is most easily performed in mice. Although mice are not susceptible to infection with wild type or vaccine strains of measles virus, they can be used for comparative evaluation of the immune responses to measles vaccines of other types. In this study we compared the immune responses in mice to a new protective alphavirus replicon particle vaccine expressing the measles virus hemagglutinin (VEE/SIN-H) with a non-protective formalin-inactivated, alum-precipitated measles vaccine (FI-MV). MV-specific IgG levels were similar, but VEE/SIN-H antibody was high avidity IgG2a with neutralizing activity while FI-MV antibody was low-avidity IgG1 without neutralizing activity. FI-MV antibody was primarily against the nucleoprotein with no priming to H. Germinal centers appeared, peaked and resolved later for FI-MV. Lymph node MV antibody-secreting cells were more numerous after FI-MV than VEE/SIN-H, but were similar in the bone marrow. VEE/SIN-H-induced T cells produced IFN-γ and IL-4 both spontaneously ex vivo and after stimulation, while FI-MV-induced T cells produced IL-4 only after stimulation. In summary, VEE/SIN-H induced a balanced T cell response and high avidity neutralizing IgG2a while FI-MV induced a type 2 T cell response, abundant plasmablasts, late germinal centers and low avidity non-neutralizing IgG1 against the nucleoprotein
Highly site-specific H2 adsorption on vicinal Si(001) surfaces
Experimental and theoretical results for the dissociative adsorption of H_2
on vicinal Si(001) surfaces are presented. Using optical second-harmonic
generation, sticking probabilities at the step sites are found to exceed those
on the terraces by up to six orders of magnitude. Density functional theory
calculations indicate the presence of direct adsorption pathways for
monohydride formation but with a dramatically lowered barrier for step
adsorption due to an efficient rehybridization of dangling orbitals.Comment: 5 pages, 4 figures, submitted to Phys. Rev. Lett. (1998). Other
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http://www.fhi-berlin.mpg.de/th/paper.htm
Review: Animal model and the current understanding of molecule dynamics of adipogenesis
Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals
Obesity, Metabolic Syndrome, and Adipocytes
Obesity and metabolic syndromes are examples whereby excess energy consumption and energy flux disruptions are causative agents of increased fatness. Because other, as yet elucidated, cellular factors may be involved and because potential treatments of these metabolic problems involve systemic agents that are not adipose depot-specific in their actions, should we be thinking of adipose depot-specific (cellular) treatments for these problems? For sure, whether treating obesity or metabolic syndrome, the characteristics of all adipose depot-specific adipocytes and stromal vascular cells should be considered. The focus of this paper is to begin to align metabolic dysfunctions with specific characteristics of adipocytes
'H, I, J, K, L, M, N, O, PEE! Get it? Pee!': Siblings' shared humour in childhood
Humour is a central feature of social interactions in childhood that has received little attention. In a sample of 86 7‐year‐old children (M age = 7.82 years, SD = 0.80), we investigated patterns and individual differences in spontaneous humour observed during free play with their older (M age = 9.55 years, SD = 0.88) or their younger sibling (M age = 5.87 years, SD = 0.96). We coded children's instances, categories, and responses to humour. We investigated the nature of children's humour on the dyadic and individual level. Humour was common, and siblings’ production of humour was highly interdependent between play partners. Dyadic humour differed according to structural features of the sibling relationship (age, gender composition), and 7‐year‐old focal children's humour varied according to gender. This study contributes to knowledge regarding the dyadic nature of children's humour and individual patterns of humour beyond the preschool years
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Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds
Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10−4), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10−5), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component
Travelling and sticky affects: : Exploring teens and sexualized cyberbullying through a Butlerian-Deleuzian- Guattarian lens
In this paper we combine the thinking of Deleuze and Guattari (1984, 1987) with Judith Butler’s (1990, 1993, 2004, 2009) work to follow the rhizomatic becomings of young people’s affective relations in a range of on- and off-line school spaces. In particular we explore how events that may be designated as sexual cyberbullying are constituted and how they are mediated by technology (such as texting or in/through social networking sites). Drawing on findings from two different studies looking at teens’ uses of and experiences with social networking sites, Arto in Denmark, and Bebo in the UK, we use this approach to think about how affects flow, are distributed, and become fixed in assemblages. We map how affects are manoeuvred and potentially disrupted by young people, suggesting that in the incidences discussed affects travel as well as stick in points of fixation. We argue that we need to grasp both affective flow and fixity in order to gain knowledge of how subjectification of the gendered/classed/racialised/sexualised body emerges. A Butlerian-Deleuzian-Guattarian frame helps us to map some of these affective complexities that shape sexualized cyberbully events; and to recognize technologically mediated lines of flight when subjectifications are at least temporarily disrupted and new terms of recognition and intelligibility staked out. Keywords
Increased proportions of circulating PD-1<sup>+</sup> CD4<sup>+</sup> memory T cells and PD-1<sup>+</sup> regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis
Background: The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. Methods:We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. Results: Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. Conclusions: Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regulatory T cells and decreased proportions of CD25+CD4+ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. Trial registration: NL44805.078.13</p
The Activation of Mucosal-Associated Invariant T (MAIT) Cells Is Affected by Microbial Diversity and Riboflavin Utilization in vitro
Recent research has demonstrated that MAIT cells are activated by individual bacterial
or yeasts species that possess the riboflavin biosynthesis pathway. However, little
is known about the MAIT cell activating potential of microbial communities and the
contribution of individual community members. Here, we analyze the MAIT cell activating
potential of a human intestinal model community (SIHUMIx) as well as intestinal
microbiota after bioreactor cultivation. We determined the contribution of individual
SIHUMIx community members to the MAIT cell activating potential and investigated
whether microbial stress can influence their MAIT cell activating potential. The MAIT cell
activating potential of SIHUMIx was directly related to the relative species abundances
in the community. We therefore suggest an additive relationship between the species
abundances and their MAIT cell activating potential. In diverse microbial communities,
we found that a low MAIT cell activating potential was associated with high microbial
diversity and a high level of riboflavin demand and vice versa. We suggest that microbial
diversity might affect MAIT cell activation via riboflavin utilization within the community.
Microbial acid stress significantly reduced the MAIT cell activating potential of SIHUMIx
by impairing riboflavin availability through increasing the riboflavin demand.We show that
MAIT cells can perceive microbial stress due to changes in riboflavin utilization and that
riboflavin availability might also play a central role for the MAIT cell activating potential of
diverse microbiota
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