449 research outputs found
Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border
BACKGROUND. Brush border microvilli are ~1-µm long finger-like projections emanating from the apical surfaces of certain, specialized absorptive epithelial cells. A highly symmetric hexagonal array of thousands of these uniformly sized structures form the brush border, which in addition to aiding in nutrient absorption also defends the large surface area against pathogens. Here, we present a molecular model of the protein cytoskeleton responsible for this dramatic cellular morphology. METHODOLOGY/PRINCIPAL FINDINGS. The model is constructed from published crystallographic and microscopic structures reported by several groups over the last 30+ years. Our efforts resulted in a single, unique, self-consistent arrangement of actin, fimbrin, villin, brush border myosin (Myo1A), calmodulin, and brush border spectrin. The central actin core bundle that supports the microvillus is nearly saturated with fimbrin and villin cross-linkers and has a density similar to that found in protein crystals. The proposed model accounts for all major proteinaceous components, reproduces the experimentally determined stoichiometry, and is consistent with the size and morphology of the biological brush border membrane. CONCLUSIONS/SIGNIFICANCE. The model presented here will serve as a structural framework to explain many of the dynamic cellular processes occurring over several time scales, such as protein diffusion, association, and turnover, lipid raft sorting, membrane deformation, cytoskeletal-membrane interactions, and even effacement of the brush border by invading pathogens. In addition, this model provides a structural basis for evaluating the equilibrium processes that result in the uniform size and structure of the highly dynamic microvilli.Boston University (Graduate Student Research Fellowship); National Institutes of Health (GM62886
Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa
Numerous species of bacteria use an elegant
regulatory mechanism known as quorum sensing to control
the expression of specific genes in a cell-density dependent
manner. In Gram-negative bacteria, quorum sensing systems
function through a cell-to-cell signal molecule (autoinducer)
that consists of a homoserine lactone with a fatty acid side
chain. Such is the case in the opportunistic human pathogen
Pseudomonas aeruginosa, which contains two quorum sensing
systems (las and rhl) that operate via the autoinducers,
N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-Lhomoserine
lactone. The study of these signal molecules has
shown that they bind to and activate transcriptional activator
proteins that specifically induce numerous P. aeruginosa
virulence genes. We report here that P. aeruginosa produces
another signal molecule, 2-heptyl-3-hydroxy-4-quinolone,
which has been designated as the Pseudomonas quinolone
signal. It was found that this unique cell-to-cell signal controlled
the expression of lasB, which encodes for the major
virulence factor, LasB elastase. We also show that the synthesis
and bioactivity of Pseudomonas quinolone signal were
mediated by the P. aeruginosa las and rhl quorum sensing
systems, respectively. The demonstration that 2-heptyl-3-
hydroxy-4-quinolone can function as an intercellular signal
sheds light on the role of secondary metabolites and shows
that P. aeruginosa cell-to-cell signaling is not restricted to
acyl-homoserine lactones. Originally published Proc. Natl. Acad. Sci, Vol. 96, No. 20, Sep. 199
Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial
Cohort Profile:Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO)
No abstract available
A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene
Within nine dentin dysplasia (type II) and dentinogenesis imperfecta (type II and III) patient/families, seven have one of four net −1 deletions within the ~2kb coding repeat domain of the DSPP gene while the remaining two patients had splice-site mutations. All frameshift mutations are predicted to change the highly soluble DSPP protein into proteins with long hydrophobic amino acid repeats that could interfere with processing of normal DSPP and/or other secreted matrix proteins. We propose that all previously reported missense, nonsense, and splice-site DSPP mutations (all associated with exons 2 and 3) result in dominant phenotypes due to disruption of signal peptide-processing and/or related biochemical events that also result in interference with protein processing. This would bring the currently known dominant forms of the human disease phenotype in agreement with the normal phenotype of the heterozygous null Dspp (−/+) mice. A study of 188 normal human chromosomes revealed a hypervariable DSPP repeat domain with extraordinary rates of change including 20 slip-replication indel events and 37 predominantly C-to-T transition SNPs. The most frequent transition in the primordial 9-bp DNA repeat was a sense-strand CpG site while a CpNpG (CAG) transition was the second most frequent SNP. Bisulfite-sequencing of genomic DNA showed that DSPP repeat can be methylated at both motifs. This suggests that, like plants and some animals, human methylate some CpNpG sequences. Analysis of 37 haplotypes of the highly variable DSPP gene from geographically diverse people suggests it may be a useful autosomal marker in human migration studies
1967: Abilene Christian College Bible Lectures - Full Text
LIFTING UP THE CHRIST”
Being the Abilene Christian College Annual Bible Lectures 1967
$3.95
Published by
ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE
ACC Station Abilene, Texa
Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity
Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality. ClinicalTrials.gov (NCT04318314)
Trust in financial services: the influence of demographics and dispositional characteristics
So far, very little attention has been paid to examining consumer perceptions of trust from an interdisciplinary perspective. The purpose of this study is to examine how consumer trusting belief and disposition to trust within the financial services sector vary on the basis of individual demographic differences in trust. The research provides new insights into how consumers with higher dispositional trust have higher institutional trust and higher trusting belief and how consumers’ trusting belief significantly differs according to their demographic background in terms of age, marital status, ethnicity and gross annual income. The findings offer useful insights for the managers in financial institutions to carefully consider the impact of the influence of these individual differences on consumer behaviour in order to serve the needs of consumers in their target market and be able to design financial products and develop trust building strategies to attract and retain them. They also call for the action of the regulators and the financial institutions to play their part in building strong institutional systems that contribute to engendering higher levels of consumer trust
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