2,417 research outputs found
Dynamics of Streptococcus mutans Transcriptome in Response to Starch and Sucrose during Biofilm Development
The combination of sucrose and starch in the presence of surface-adsorbed salivary α-amylase and bacterial glucosyltransferases increase the formation of a structurally and metabolically distinctive biofilm by Streptococcus mutans. This host-pathogen-diet interaction may modulate the formation of pathogenic biofilms related to dental caries disease. We conducted a comprehensive study to further investigate the influence of the dietary carbohydrates on S. mutans-transcriptome at distinct stages of biofilm development using whole genomic profiling with a new computational tool (MDV) for data mining. S. mutans UA159 biofilms were formed on amylase-active saliva coated hydroxyapatite discs in the presence of various concentrations of sucrose alone (ranging from 0.25 to 5% w/v) or in combination with starch (0.5 to 1% w/v). Overall, the presence of sucrose and starch (suc+st) influenced the dynamics of S. mutans transcriptome (vs. sucrose alone), which may be associated with gradual digestion of starch by surface-adsorbed amylase. At 21 h of biofilm formation, most of the differentially expressed genes were related to sugar metabolism, such as upregulation of genes involved in maltose/maltotriose uptake and glycogen synthesis. In addition, the groEL/groES chaperones were induced in the suc+st-biofilm, indicating that presence of starch hydrolysates may cause environmental stress. In contrast, at 30 h of biofilm development, multiple genes associated with sugar uptake/transport (e.g. maltose), two-component systems, fermentation/glycolysis and iron transport were differentially expressed in suc+st-biofilms (vs. sucrose-biofilms). Interestingly, lytT (bacteria autolysis) was upregulated, which was correlated with presence of extracellular DNA in the matrix of suc+st-biofilms. Specific genes related to carbohydrate uptake and glycogen metabolism were detected in suc+st-biofilms in more than one time point, indicating an association between presence of starch hydrolysates and intracellular polysaccharide storage. Our data show complex remodeling of S. mutans-transcriptome in response to changing environmental conditions in situ, which could modulate the dynamics of biofilm development and pathogenicity
Power analysis for genome-wide association studies
Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.</p
Recommended from our members
Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes
Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity
Ernst Freund as Precursor of the Rational Study of Corporate Law
Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe
Mediating Solidarity
With the apparent increase in the number of alternative political media, political pluralists are again faced with the question: does the proliferation of subaltern counter-publics lead to a multiplication of forces? Fragmentation in political culture is fuelled by the rise of identity politics that focuses on consumption not production. Party allegiances and class alliances give way to more fluid and informal networks of action. Postmodern theorists celebrate fragmentation because it allows the recognition of diversity in political desires, acknowledges difference between individuals and debunks the myth of homogenous political units leading ultimately to liberation. But for political efficacy there must be more than the apparent freedom that comes with embracing difference and diversity. This article argues that if we accept the description of society as fragmented, in order to create a viable political community then solidarity is crucial. In a global economy, solidarity can be mediated through new communication technologies but the challenge is to articulate the politics online with actual movements and struggles on the ground
Chronic non-specific low back pain - sub-groups or a single mechanism?
Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a
considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions
for chronic non-specific low back pain indicate limited effectiveness for most commonly applied
interventions and approaches.
Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of
effectiveness is at odds with their clinical experience of managing patients with back pain. A
common explanation for this discrepancy is the perceived heterogeneity of patients with chronic
non-specific low back pain. It is felt that the effects of treatment may be diluted by the application
of a single intervention to a complex, heterogeneous group with diverse treatment needs. This
argument presupposes that current treatment is effective when applied to the correct patient.
An alternative perspective is that the clinical trials are correct and current treatments have limited
efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important
that the sub-grouping paradigm is closely examined. This paper argues that there are numerous
problems with the sub-grouping approach and that it may not be an important reason for the
disappointing results of clinical trials. We propose instead that current treatment may be ineffective
because it has been misdirected. Recent evidence that demonstrates changes within the brain in
chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of
cortical reorganisation and degeneration. This perspective offers interesting insights into the
chronic low back pain experience and suggests alternative models of intervention.
Summary: The disappointing results of clinical research are commonly explained by the failure of
researchers to adequately attend to sub-grouping of the chronic non-specific low back pain
population. Alternatively, current approaches may be ineffective and clinicians and researchers may
need to radically rethink the nature of the problem and how it should best be managed
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector
The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30
- …