In a peach basket hat made for two

Gift of Dr. Mary Jane Esplen.Piano vocal [instrumentation]'Neath your inverted bonnet [first line]In a "peach basket hat" made for two [first line of refrain]E flat [key]Tempo di valse [tempo]Popular song [form/genre]Couple sitting on dock beneath a basket hat [illustration]Publisher's advertisement on inside front and back cover [note

Dependence of NO rotational photoionization propensity rules on electron kinetic energy

In order to study the effect of photoelectron kinetic energy on rotational photoionization propensity rules, rotationally resolved laser photoelectron spectra were measured for excitation of specific rovibronic levels in the D 2Sigma+ (3psigma) Rydberg state of NO and their subsequent ionization by radiation at several wavelengths. The measured and calculated ion rotational branching ratios both show a significant dependence on photoelectron energy. Comparison between experimental data and theoretical calculations suggests that a strong DeltaN=0 peak in the spectra is caused by an interaction between particular vibronic levels of the A 2Sigma+ (v=4) and D 2Sigma+ (v=0) Rydberg states

Performance of an environmental test to detect Mycobacterium bovis infection in badger social groups

A study by Courtenay and others (2006) demonstrated that the probability of detecting Mycobacterium bovis by PCR in soil samples from the spoil heaps of main badger setts correlated with the prevalence of excretion (infectiousness) of captured badgers belonging to the social group. It has been proposed that such a test could be used to target badger culling to setts containing infectious animals (Anon 2007). This short communication discusses the issues surrounding this concept, with the intention of dispelling any misconceptions among relevant stakeholders (farmers, policy makers and conservationists)

IL-21 receptor expression in human tendinopathy

The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward and early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly up regulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy

MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury

Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Objectives: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Methods: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Results: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. Conclusion: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders

Validity, practical utility, and reliability of the activPAL in preschool children

<p>Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g. sedentary time) contributing to positive energy balance in early childhood. For pre-school children, single unit monitors such as the activPALTM are promising. However, validation is required as activity patterns differ from adults.</p> <p>Methods: Thirty pre-school children participated in a validation study. Children were videoed for one hour undertaking usual nursery activity while wearing an activPALTM. Video (criterion method) was analyzed on a second-by-second basis to categorise posture and activity. This was compared with the corresponding activPALTM output. In a subsequent sub-study investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24-hour periods.</p> <p>Results: A total of 97,750 seconds of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), walk (16%); with 3% of time in nonsit/lie/upright postures (e.g. crawl/crouch/kneel-up). Sensitivity for the overall total time matched seconds detected as activPALTM ‘sit/lie’ was 86.7%, specificity 97.1%, and positive predictive value (PPV) 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1-97.4), specificity 97.3% (94.9-99.2), PPV 97.0% (91.5-99.1). The activPALTM underestimated total time spent sitting (mean difference -4.4%, p<0.01), and overestimated time standing (mean difference 7.1%, p<0.01). There was no difference in overall % time categorised as ‘walk’ (p=0.2). The monitors were well tolerated by children during a seven day period of free-living activity. In the reliability study, at least five days of monitoring were required to obtain an intraclass correlation coefficient of ≥0.8 for time spent sit/lie according to activPALTM output.</p> <p>Conclusion: The activPAL had acceptable validity, practical utility, and reliability for the measurement of posture and activity during freeliving activities in pre-school children.</p&gt

Characterization of MSB Synapses in Dissociated Hippocampal Culture with Simultaneous Pre- and Postsynaptic Live Microscopy

Multisynaptic boutons (MSBs) are presynaptic boutons in contact with multiple postsynaptic partners. Although MSB synapses have been studied with static imaging techniques such as electron microscopy (EM), the dynamics of individual MSB synapses have not been directly evaluated. It is known that the number of MSB synapses increases with synaptogenesis and plasticity but the formation, behavior, and fate of individual MSB synapses remains largely unknown. To address this, we developed a means of live imaging MSB synapses to observe them directly over time. With time lapse confocal microscopy of GFP-filled dendrites in contact with VAMP2-DsRed-labeled boutons, we recorded both MSBs and their contacting spines hourly over 15 or more hours. Our live microscopy showed that, compared to spines contacting single synaptic boutons (SSBs), MSB-contacting spines exhibit elevated dynamic behavior. These results are consistent with the idea that MSBs serve as intermediates in synaptic development and plasticity

Attenuation of Dupuytren’s fibrosis via targeting of the STAT-1 modulated IL-13RA1 response

Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren’s disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren’s as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease