4,690 research outputs found
A simplified biomimetic temperature logger for recording intertidal barnacle body temperatures
published_or_final_versio
Biomineralization mediated by anaerobic methane-consuming cell consortia
published_or_final_versio
Classical Stability of the Galileon
We consider the classical equations of motion for a single Galileon field
with generic parameters in the presence of non-relativistic sources. We
introduce the concept of absolute stability of a theory: if one can show that a
field at a single point---like infinity for instance---in spacetime is stable,
then stability of the field over the rest of spacetime is guaranteed for any
positive energy source configuration. The Dvali-Gabadadze-Porrati (DGP) model
is stable in this manner, and previous studies of spherically symmetric
solutions suggest that certain classes of the single field Galileon (of which
the DGP model is a subclass) may have this property as well. We find, however,
that when general solutions are considered this is not the case. In fact, when
considering generic solutions there are no choices of free parameters in the
Galileon theory that will lead to absolute stability except the DGP choice. Our
analysis indicates that the DGP model is an exceptional choice among the large
class of possible single field Galileon theories. This implies that if general
solutions (non-spherically symmetric) exist they may be unstable. Given
astrophysical motivation for the Galileon, further investigation into these
unstable solutions may prove fruitful.Comment: 23 pages, 3 figure
Seeds Buffering for Information Spreading Processes
Seeding strategies for influence maximization in social networks have been
studied for more than a decade. They have mainly relied on the activation of
all resources (seeds) simultaneously in the beginning; yet, it has been shown
that sequential seeding strategies are commonly better. This research focuses
on studying sequential seeding with buffering, which is an extension to basic
sequential seeding concept. The proposed method avoids choosing nodes that will
be activated through the natural diffusion process, which is leading to better
use of the budget for activating seed nodes in the social influence process.
This approach was compared with sequential seeding without buffering and single
stage seeding. The results on both real and artificial social networks confirm
that the buffer-based consecutive seeding is a good trade-off between the final
coverage and the time to reach it. It performs significantly better than its
rivals for a fixed budget. The gain is obtained by dynamic rankings and the
ability to detect network areas with nodes that are not yet activated and have
high potential of activating their neighbours.Comment: Jankowski, J., Br\'odka, P., Michalski, R., & Kazienko, P. (2017,
September). Seeds Buffering for Information Spreading Processes. In
International Conference on Social Informatics (pp. 628-641). Springe
Mapping the genetic architecture of gene expression in human liver
Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process. © 2008 Schadt et al
Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood
OBJECTIVE:
Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance.
METHODS:
Foxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test.
RESULTS:
A higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA.
CONCLUSIONS:
Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.postprin
Computational Analysis and Prediction of the Binding Motif and Protein Interacting Partners of the Abl SH3 Domain
Protein-protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains, such as Src Homology 2 and 3 (SH2 and SH3) domains, which bind to specific sequence and structural motifs. It is important but challenging to determine the binding specificity of these domains accurately and to predict their physiological interacting partners. In this study, the interactions between 35 peptide ligands (15 binders and 20 non-binders) and the Abl SH3 domain were analyzed using molecular dynamics simulation and the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. The calculated binding free energies correlated well with the rank order of the binding peptides and clearly distinguished binders from non-binders. Free energy component analysis revealed that the van der Waals interactions dictate the binding strength of peptides, whereas the binding specificity is determined by the electrostatic interaction and the polar contribution of desolvation. The binding motif of the Abl SH3 domain was then determined by a virtual mutagenesis method, which mutates the residue at each position of the template peptide relative to all other 19 amino acids and calculates the binding free energy difference between the template and the mutated peptides using the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. A single position mutation free energy profile was thus established and used as a scoring matrix to search peptides recognized by the Abl SH3 domain in the human genome. Our approach successfully picked ten out of 13 experimentally determined binding partners of the Abl SH3 domain among the top 600 candidates from the 218,540 decapeptides with the PXXP motif in the SWISS-PROT database. We expect that this physical-principle based method can be applied to other protein domains as well
Holographic Josephson Junctions and Berry holonomy from D-branes
We construct a holographic model for Josephson junctions with a defect system
of a Dp brane intersecting a D(p+2) brane. In addition to providing a
geometrical picture for the holographic dual, this leads us very naturally to
suggest the possibility of non-Abelian Josephson junctions characterized in
terms of the topological properties of the branes. The difference between the
locations of the endpoints of the Dp brane on either side of the defect
translates into the phase difference of the condensate in the Josephson
junction. We also add a magnetic flux on the D(p+2) brane and allow it evolve
adiabatically along a closed curve in the space of the magnetic flux, while
generating a non-trivial Berry holonomy.Comment: 20 pages, 2 figure
Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats
Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.published_or_final_versio
Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.
In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors
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