289 research outputs found
Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage
Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of cell signalling proteins, present in raised concentrations in OA joints, can be classified into pro-inflammatory and anti-inflammatory groups. They mediate cartilage degradation through several mechanisms, primarily the up-regulation of matrix metalloproteinases (MMPs), a group of collagen-degrading enzymes. In this paper we show that the interactions of cytokines within cartilage have a crucial role to play in OA progression and treatment. We develop a four-variable ordinary differential equation model for the interactions between pro- and anti-inflammatory cytokines, MMPs and fibronectin fragments (Fn-fs), a by-product of cartilage degradation and upregulator of cytokines. We show that the model has four classes of dynamic behaviour: homoeostasis, bistable inflammation, tristable inflammation and persistent inflammation. We show that positive and negative feedbacks controlling cytokine production rates can determine either a pre-disposition to OA or initiation of OA. Further, we show that manipulation of cytokine, MMP and Fn-fs levels can be used to treat OA, but we suggest that multiple treatment targets may be essential to halt or slow disease progression
Absence of Membrane Phosphatidylcholine Does Not Affect Virulence and Stress Tolerance Phenotypes in the Opportunistic Pathogen Pseudomonas aeruginosa
During growth in presence of choline, both laboratory and clinical Pseudomonas aeruginosa strains synthesize phosphatidylcholine (PC), and PC makes up âŒ4% of the total membrane phospholipid content. In all the strains tested, PC synthesis occurred only when choline is provided exogenously. Mutants defective in synthesis of PC were generated in the strain backgrounds PAO1 and PA14. Minimum inhibitory concentration studies testing sensitivity of PC-deficient strains towards various antibiotics and cationic antimicrobial peptides revealed no differences as compared to wild-type strains. Mutants incapable of synthesizing PC were also found to be unaffected in motility and biofilm formation on abiotic surfaces, colonization of biotic surfaces and virulence in a mouse infection model. A global phenotypic microarray was further used to identify conditions wherein membrane PC may play a role of in P. aeruginosa. No culture conditions were identified wherein wild-type and PC-deficient mutants showed phenotypic differences. Membrane PC may serve a highly specific role during P. aeruginosa interactions with its eukaryotic hosts based on all the clinical strains tested retaining the ability to synthesize it during availability of choline
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Selenium Toxicity to Honey Bee (Apis mellifera L.) Pollinators: Effects on Behaviors and Survival
We know very little about how soil-borne pollutants such as selenium (Se) can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER) and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae) foragers. Antennae and proboscises were stimulated with both organic (selenomethionine) and inorganic (selenate) forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate), reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other insect guilds
Biofluid Biomarkers in Huntington's Disease
Huntington's disease (HD) is a chronic progressive neurodegenerative condition where new markers of disease progression are needed. So far no disease-modifying interventions have been found, and few interventions have been proven to alleviate symptoms. This may be partially explained by the lack of reliable indicators of disease severity, progression, and phenotype.Biofluid biomarkers may bring advantages in addition to clinical measures, such as reliability, reproducibility, price, accuracy, and direct quantification of pathobiological processes at the molecular level; and in addition to empowering clinical trials, they have the potential to generate useful hypotheses for new drug development.In this chapter we review biofluid biomarker reports in HD, emphasizing those we feel are likely to be closest to clinical applicability
Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe
First measurement of the |t|-dependence of coherent J/Ï photonuclear production
The first measurement of the cross section for coherent J/Ï photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral PbâPb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/Ï produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3â1.4)Ă10â3.
The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent BalitskyâKovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio
First measurement of coherent Ï0 photoproduction in ultra-peripheral XeâXe collisions at âsNN = 5.44 TeV
The first measurement of the coherent photoproduction of Ï0 vector mesons in ultra-peripheral XeâXe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA Îłp data and ÎłâPb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+XeâÏ0+Xe+Xe process, measured at midrapidity through the decay channel Ï0âÏ+Ïâ, is found to be dÏ/dy=131.5±5.6(stat.)â16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent Ï0 photoproduction at a centre-of-mass energy per nucleon of the ÎłA system of WÎłA,n=65 GeV is found to be consistent with a power-law behaviour Ï(ÎłAâÏ0A)âAα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio
Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection
- âŠ