The Role of TLR2 in Infection and Immunity

Toll-like receptors (TLRs) are recognition molecules for multiple pathogens, including bacteria, viruses, fungi, and parasites. TLR2 forms heterodimers with TLR1 and TLR6, which is the initial step in a cascade of events leading to significant innate immune responses, development of adaptive immunity to pathogens and protection from immune sequelae related to infection with these pathogens. This review will discuss the current status of TLR2 mediated immune responses by recognition of pathogen-associated molecular patterns (PAMPS) on these organisms. We will emphasize both canonical and non-canonical responses to TLR2 ligands with emphasis on whether the inflammation induced by these responses contributes to the disease state or to protection from diseases

Does the new rugby union scrum sequence positively influence the hooker's in situ spinal kinematics?

Background: Scrummaging is unique to rugby union and involves 2 ‘packs’ of 8 players competing to regain ball possession. Intending to serve as a quick and safe method to restart the game, injury prevalence during scrummaging necessitates further evaluation of this environment. Aims: The aim of this study was to determine the effect of scrummage engagement sequences on spinal kinematics of the hooker. The conditions investigated were: (1) live competitive scrummaging using the new ‘crouch, bind, set’ sequence; (2) live competitive scrummaging using the old ‘crouch touch pause engage’ sequence and (3) training scrummaging using a scrum machine. Methods: Inertial sensors provided three-dimensional kinematic data across 5 spinal regions. Participants (n=29) were adult, male community club and university-level hookers. Results: Engagement sequence had no effect on resultant kinematics of any spinal region. Machine scrummaging resulted in lesser magnitudes of motion in the upper spinal regions. Around two-thirds of the total available cervical motion was utilised during live scrummaging. Conclusions: This study indicates that the most recent laws do not influence the spinal kinematics of the hooker during live scrummaging; however, there may be other benefits from these law changes that fall outside the scope of this investigation

Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet

BACKGROUND: Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. In this study, we identified gene expression profiles that characterize P. gingivalis, C. pneumoniae, and Western diet (WD) at acute and chronic time points in aortas of Apolipoprotein E (ApoE-/-) mice. RESULTS: At the chronic time point, we observed that P. gingivalis was associated with a high number of unique differentially expressed genes compared to C. pneumoniae or WD. For the top 500 differentially expressed genes unique to each group, we observed a high percentage (76%) that exhibited decreased expression in P. gingivalis-treated mice in contrast to a high percentage (96%) that exhibited increased expression in WD mice. C. pneumoniae treatment resulted in approximately equal numbers of genes that exhibited increased and decreased expression. Gene Set Enrichment Analysis (GSEA) revealed distinct stimuli-associated phenotypes, including decreased expression of mitochondrion, glucose metabolism, and PPAR pathways in response to P. gingivalis but increased expression of mitochondrion, lipid metabolism, carbohydrate and amino acid metabolism, and PPAR pathways in response to C. pneumoniae; WD was associated with increased expression of immune and inflammatory pathways. DAVID analysis of gene clusters identified by two-way ANOVA at acute and chronic time points revealed a set of core genes that exhibited altered expression during the natural progression of atherosclerosis in ApoE-/- mice; these changes were enhanced in P. gingivalis-treated mice but attenuated in C. pneumoniae-treated mice. Notable differences in the expression of genes associated with unstable plaques were also observed among the three pro-atherogenic stimuli. CONCLUSIONS: Despite the common outcome of P. gingivalis, C. pneumoniae, and WD on the induction of vascular inflammation and atherosclerosis, distinct gene signatures and pathways unique to each pro-atherogenic stimulus were identified. Our results suggest that pathogen exposure results in dysregulated cellular responses that may impact plaque progression and regression pathways

Thermal reversion of spirooxazine in ionic liquids containing the [NTf2]- anion

We have compared the rate of thermal reversion of Spirooxazine (SO) from its merocyanine (MC) form within ionic liquids and molecular solvents. Et(30) and Kamlet-Taft parameter studies indicate ILs are comparable to polar protic and aprotic solvents. The observed reversion kinetics within the ionic liquids were slower than that of molecular solvents with similar polarity, indicating a greater degree of interactions between the ionic liquid ions and the zwitterionic MC isomer, which led to increased lifetimes for the MC-ion complexes. Pre-metathesis cleaning of precursor salts was found to be necessary in order to obtain spectroscopic grade ILs for physiochemical analysis using solvatochromic probe dyes

Outcomes of a Modified CALGB 19802 Regimen in Adult Acute Lymphoblastic Leukemia

We analyzed the efficacy and toxicity of a modified Cancer and Leukemia Group B (CALGB) 19802 regimen in adult acute lymphoblastic leukemia (ALL). From February 2002 to August 2005, 25 adults with untreated ALL were enrolled in the study. Compared to the original regimen, the modified CALGB 19802 regimen consisted of a 4-drug induction (cyclophosphamide, daunorubicin, vincristine, and prednisone) instead of a 5-drug induction (L-asparaginase was added to the previous regimen). This was followed by high-dose methotrexate (1,000 mg/m2×3 days) and cytarabine (2,000 mg/m2×4 days) for the consolidation cycles. High-dose systemic and intrathecal methotrexate was given for central nervous system prophylaxis. Twenty-three patients (92%) achieved a complete remission (CR), and two patients (8%) had refractory disease. With a median follow-up of 21.5 months, 10 patients (40%) were alive and continued to be in CR. The 3-yr probability of an event-free survival and the overall survival were 39.0% and 47.4%, respectively. Treatment related mortality and major grade 3 to 4 neurotoxicity occurred in 1 patient and 3 patients, respectively. The modified CALGB 19802 regimen demonstrated a high remission rate and a favorable survival rate

Partonic flow and ϕ\phi-meson production in Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

We present first measurements of the $\phi$-meson elliptic flow ($v_{2}(p_{T})$) and high statistics $p_{T}$ distributions for different centralities from $\sqrt{s_{NN}}$ = 200 GeV Au+Au collisions at RHIC. In minimum bias collisions the $v_{2}$ of the $\phi$ meson is consistent with the trend observed for mesons. The ratio of the yields of the $\Omega$ to those of the $\phi$ as a function of transverse momentum is consistent with a model based on the recombination of thermal $s$ quarks up to $p_{T}\sim 4$ GeV/$c$, but disagrees at higher momenta. The nuclear modification factor ($R_{CP}$) of $\phi$ follows the trend observed in the $K^{0}_{S}$ mesons rather than in $\Lambda$ baryons, supporting baryon-meson scaling. Since $\phi$-mesons are made via coalescence of seemingly thermalized $s$ quarks in central Au+Au collisions, the observations imply hot and dense matter with partonic collectivity has been formed at RHIC.Comment: 6 pages, 4 figures, submit to PR

Plasma Wakefield Acceleration with a Modulated Proton Bunch

The plasma wakefield amplitudes which could be achieved via the modulation of a long proton bunch are investigated. We find that in the limit of long bunches compared to the plasma wavelength, the strength of the accelerating fields is directly proportional to the number of particles in the drive bunch and inversely proportional to the square of the transverse bunch size. The scaling laws were tested and verified in detailed simulations using parameters of existing proton accelerators, and large electric fields were achieved, reaching 1 GV/m for LHC bunches. Energy gains for test electrons beyond 6 TeV were found in this case.Comment: 9 pages, 7 figure

The energy dependence of ptp_t angular correlations inferred from mean-ptp_{t} fluctuation scale dependence in heavy ion collisions at the SPS and RHIC

We present the first study of the energy dependence of $p_t$ angular correlations inferred from event-wise mean transverse momentum fluctuations in heavy ion collisions. We compare our large-acceptance measurements at CM energies $\sqrt{s_{NN}} =$ 19.6, 62.4, 130 and 200 GeV to SPS measurements at 12.3 and 17.3 GeV. $p_t$ angular correlation structure suggests that the principal source of $p_t$ correlations and fluctuations is minijets (minimum-bias parton fragments). We observe a dramatic increase in correlations and fluctuations from SPS to RHIC energies, increasing linearly with $\ln \sqrt{s_{NN}}$ from the onset of observable jet-related fluctuations near 10 GeV.Comment: 10 pages, 4 figure