869 research outputs found
Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules
Background:
Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p>
Methods:
An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p>
Results:
CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p>
Conclusions:
CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p>
Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor
Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors
Orbifold equivalence for finite density QCD and effective field theory
In the large N_c limit, some apparently different gauge theories turn out to
be equivalent due to large N_c orbifold equivalence. We use effective field
theory techniques to explore orbifold equivalence, focusing on the specific
case of a recently discovered relation between an SO(2N_c) gauge theory and
QCD. The equivalence to QCD has been argued to hold at finite baryon chemical
potential, \mu_B, so long as one deforms the SO(2N_c) theory by certain
"double-trace" terms. The deformed SO(2N_c) theory can be studied without a
sign problem in the chiral limit, in contrast to SU(N_c) QCD at finite \mu_B.
The purpose of the double-trace deformation in the SO(2N_c) theory is to
prevent baryon number symmetry from breaking spontaneously at finite density,
which is necessary for the equivalence to large N_c QCD to be valid. The
effective field theory analysis presented here clarifies the physical
significance of double-trace deformations, and strongly supports the proposed
equivalence between the deformed SO(2N_c) theory and large N_c QCD at finite
density.Comment: 39 pages, 5 figures, 2 tables. v2: Minor typo fixes and
clarification
Physiotherapy-supervised mobilization and exercise following cardiac surgery: a national questionnaire survey in Sweden
The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model
Both Grand Unified symmetries and discrete flavour symmetries are appealing
ways to describe apparent structures in the gauge and flavour sectors of the
Standard Model. Both symmetries put constraints on the high energy behaviour of
the theory. This can give rise to unexpected interplay when building models
that possess both symmetries. We investigate on the possibility to combine a
Pati-Salam model with the discrete flavour symmetry that gives rise to
quark-lepton complementarity. Under appropriate assumptions at the GUT scale,
the model reproduces fermion masses and mixings both in the quark and in the
lepton sectors. We show that in particular the Higgs sector and the running
Yukawa couplings are strongly affected by the combined constraints of the Grand
Unified and family symmetries. This in turn reduces the phenomenologically
viable parameter space, with high energy mass scales confined to a small region
and some parameters in the neutrino sector slightly unnatural. In the allowed
regions, we can reproduce the quark masses and the CKM matrix. In the lepton
sector, we reproduce the charged lepton masses, including bottom-tau
unification and the Georgi-Jarlskog relation as well as the two known angles of
the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse
hierarchy, and only allowing the neutrino parameters to spread into a range of
values between and , with .
Finally, our model suggests that the reactor mixing angle is close to its
current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for
publication in JHE
A tunable carbon nanotube electromechanical oscillator
Nanoelectromechanical systems (NEMs) hold promise for a number of scientific
and technological applications. In particular, NEMs oscillators have been
proposed for use in ultrasensitive mass detection, radio-frequency signal
processing, and as a model system for exploring quantum phenomena in
macroscopic systems. Perhaps the ultimate material for these applications is a
carbon nanotube. They are the stiffest material known, have low density,
ultrasmall cross-sections and can be defect-free. Equally important, a nanotube
can act as a transistor and thus may be able to sense its own motion. In spite
of this great promise, a room-temperature, self-detecting nanotube oscillator
has not been realized, although some progress has been made. Here we report the
electrical actuation and detection of the guitar-string-like oscillation modes
of doubly clamped nanotube oscillators. We show that the resonance frequency
can be widely tuned and that the devices can be used to transduce very small
forces.Comment: 9 pages, 3 figure
Loss of ELK1 has differential effects on age-dependent organ fibrosis
ETS domain-containing protein-1 (ELK1) is a transcription factor important in regulating αvβ6 integrin expression. αvβ6 integrins activate the profibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and are increased in the alveolar epithelium in idiopathic pulmonary fibrosis (IPF). IPF is a disease associated with aging and therefore we hypothesised that aged animals lacking Elk1 globally would develop spontaneous fibrosis in organs where αvβ6 mediated TGFβ activation has been implicated. Here we identify that Elk1-knockout (Elk1−/0) mice aged to one year developed spontaneous fibrosis in the absence of injury in both the lung and the liver but not in the heart or kidneys. The lungs of Elk1−/0 aged mice demonstrated increased collagen deposition, in particular collagen 3α1, located in small fibrotic foci and thickened alveolar walls. Despite the liver having relatively low global levels of ELK1 expression, Elk1−/0 animals developed hepatosteatosis and fibrosis. The loss of Elk1 also had differential effects on Itgb1, Itgb5 and Itgb6 expression in the four organs potentially explaining the phenotypic differences in these organs. To understand the potential causes of reduced ELK1 in human disease we exposed human lung epithelial cells and murine lung slices to cigarette smoke extract, which lead to reduced ELK1 expression andmay explain the loss of ELK1 in human disease. These data support a fundamental role for ELK1 in protecting against the development of progressive fibrosis via transcriptional regulation of beta integrin subunit genes, and demonstrate that loss of ELK1 can be caused by cigarette smoke
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