Early stage fatigue damage occurs in bovine tendon fascicles in the absence of changes in mechanics at either the gross or micro-structural level

Many tendon injuries are believed to result from repetitive motion or overuse, leading to the accumulation of micro-damage over time. In vitro fatigue loading can be used to characterise damage during repeated use and investigate how this may relate to the aetiology of tendinopathy. This study considered the effect of fatigue loading on fascicles from two functionally distinct bovine tendons: the digital extensor and deep digital flexor. Micro-scale extension mechanisms were investigated in fascicles before or after a period of cyclic creep loading, comparing two different measurement techniques - the displacement of a photo-bleached grid and the use of nuclei as fiducial markers. Whilst visual damage was clearly identified after only 300 cycles of creep loading, these visual changes did not affect either gross fascicle mechanics or fascicle microstructural extension mechanisms over the 900 fatigue cycles investigated. However, significantly greater fibre sliding was measured when observing grid deformation rather than the analysis of nuclei movement. Measurement of microstructural extension with both techniques was localised and this may explain the absence of change in microstructural deformation in response to fatigue loading. Alternatively, the data may demonstrate that fascicles can withstand a degree of matrix disruption with no impact on mechanics. Whilst use of a photo-bleached grid to directly measure the collagen is the best indicator of matrix deformation, nuclei tracking may provide a better measure of the strain perceived directly by the cells

Breadth First Search Vectorization on the Intel Xeon Phi

Breadth First Search (BFS) is a building block for graph algorithms and has recently been used for large scale analysis of information in a variety of applications including social networks, graph databases and web searching. Due to its importance, a number of different parallel programming models and architectures have been exploited to optimize the BFS. However, due to the irregular memory access patterns and the unstructured nature of the large graphs, its efficient parallelization is a challenge. The Xeon Phi is a massively parallel architecture available as an off-the-shelf accelerator, which includes a powerful 512 bit vector unit with optimized scatter and gather functions. Given its potential benefits, work related to graph traversing on this architecture is an active area of research. We present a set of experiments in which we explore architectural features of the Xeon Phi and how best to exploit them in a top-down BFS algorithm but the techniques can be applied to the current state-of-the-art hybrid, top-down plus bottom-up, algorithms. We focus on the exploitation of the vector unit by developing an improved highly vectorized OpenMP parallel algorithm, using vector intrinsics, and understanding the use of data alignment and prefetching. In addition, we investigate the impact of hyperthreading and thread affinity on performance, a topic that appears under researched in the literature. As a result, we achieve what we believe is the fastest published top-down BFS algorithm on the version of Xeon Phi used in our experiments. The vectorized BFS top-down source code presented in this paper can be available on request as free-to-use software

Epigenetic Mechanisms Governing Behavioral Reprogramming In The Ant Camponotus Floridanus

Eusocial insect colonies divide behaviors among specialist groups called castes. In some species, caste identity is determined by the interaction of endogenous (e.g. genomic) and exogenous (e.g. juvenile hormone from nurses) signals during larval development, suggesting epigenetic mechanisms underlie plastic traits tied to caste identity. Previous work demonstrated a link between patterns of histone H3 lysine 27 acetylation (H3K27ac) and caste-specific gene expression in Major and Minor workers of the ant Camponotus floridanus, and we hypothesized caste-specific behaviors such as foraging may be similarly regulated by histone acetylation. To test this hypothesis, we fed mature (~30d old) Majors and Minors with histone deacetylase inhibitors (HDACi), and CBP-dependent histone acetyl transferase inhibitors (HATi). We observed foraging enhancement after HDACi, and foraging suppression after HATi in Minors. Curiously, we did not observe increased foraging in HDACi treated mature (~30d) Majors. However, HDACi injections in callow (0-1d old) Majors succeeded in causing stable reprogramming of foraging behavior, indicating a critical period, or ‘window’ of epigenetic sensitivity to HDACi exists in young majors. To address this possibility, we injected Majors with HDACi in a time course and observed juvenile (d0-d5) Majors are susceptible to reprogramming, whereas mature (d10) Majors are not. To assess innate differences in the brain between castes, we conducted an RNA-seq study in untreated Major and Minor workers 0, 5, and 10 days old, and detected caste-specific patterns of juvenile hormone and ecdysone signaling. Finally, to characterize the transcriptional and epigenetic effects of reprogramming, we conducted RNA-seq in HDACi treated Major brains, and detected consistent upregulation of members of the neuron restrictive silencing factor (NRSF/REST) repressive complex (e.g. CoREST, RPD3, ttk). Notably, the top downregulated gene after HDACi is juvenile hormone esterase (JHe), which antagonizes JH signaling and inhibits foraging behavior in many eusocial insects. Thus, our results suggest REST/CoREST mediated repression of JHe may be a significant source of stable changes to foraging in behaviorally reprogrammed Majors

Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells

Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1ß-stimulated expression of matrix metalloproteinases (MMP)-3 and MMP-1 in human tendon-derived cells. We have now tested additional fluoroquinolones and investigated whether they have a similar effect on expression of MMP-13. Tendon cells were incubated for two periods of 48?h with or without fluoroquinolones and IL-1ß. Total ribonucleic acid (RNA) was assayed for MMP messenger RNA by relative quantitative reverse transcriptase polymerase chain reaction, with normalization for glyceraldehyde-3-phosphate dehydrogenase mRNA. Samples of supernatant medium were assayed for MMP output by activity assays. MMP-13 was expressed by tendon cells at lower levels than MMP-1, and was stimulated typically 10- to 100-fold by IL-1ß. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1ß-stimulated MMP-1 mRNA expression. Both the inhibition of MMP-13 and the potentiation of MMP-1 expression by fluoroquinolones were accompanied by corresponding changes in IL-1ß-stimulated MMP output. The non-fluorinated quinolone nalidixic acid had lesser or no effects. Fluoroquinolones show contrasting effects on the expression of the two collagenases MMP-1 and MMP-13, indicating specific effects on MMP gene regulation

Reach modelling for drive-up self-service

People using a self-service terminal such as an automated teller machine (ATM) tend to adjust their physical position throughout a transaction. This is particularly apparent with terminals that are designed to be used from a vehicle (i.e. drive up automated teller machines or ATMs). Existing predictive tools tend to focus on static reach and provide limited predictions for how far people are willing to stretch to complete a task. Drive-up self-service products have 3 main challenges: the variability of vehicles, people and driver behaviour. Such conventional tools are therefore of limited use in understanding how much people are willing to move to use a self-service terminal. Work is described to build in-house predictive models based on 2 large empirical studies of reach in a drive up installation. These 2 studies assessed comfortable and extended reach from 10 vehicle categories. Extended reach was defined as stretching/leaning as far as participants would normally be willing to in order to complete a drive-up transaction. Findings from these studies indicated that participants are prepared to adopt more extreme postures at drive-up than in other situations with extended reach at drive-up being significantly different to what might be seen at a walk-up kiosk

Inhibition of interleukin-1β-stimulated collagenase and stromelysin expression in human tendon fibroblasts by epigallocatechin gallate ester

The medicinal benefits of green tea (Camellia sinensis) consumption have been attributed to bioavailable polyphenols, notably epigallocatechin gallate (EGCG). We have assessed the effects of EGCG and its non-esterified counterpart EGC on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, and the stromelysin, MMP-3, in human tendon-derived fibroblasts. Interleukin (IL)-1ß increased MMP-1, -3 and -13 mRNA and output at least 30-fold. EGCG reduced this stimulation, by 20–30% at 2.5 µM and more than 80% at 25 µM, and had a smaller effect on MMP-2 mRNA expression, which was not stimulated by IL-1ß. In all experiments EGCG was at least 10-fold more potent than EGC. EGCG reduced the stimulation of p54 JNK/SAPK phosphorylation by IL-1ß but did not affect p38 MAPK phosphorylation, the degradation of I?B or the activating phosphorylation of NF?B. We conclude that EGCG reduces the IL-1-stimulated expression of both collagenase and stromelysin mRNA species, an effect which may be mediated by inhibition of the JNK/SAPK pathway. Taken together with previous reports of EGCG effects on the expression and/or activity of gelatinases and aggrecanases, our results underline the importance of extracellular matrix breakdown as a potential target for the actions of green tea polyphenols

Fascicles and the interfascicular matrix show adaptation for fatigue resistance in energy storing tendons

Tendon is composed of rope-like fascicles, bound together by interfascicular matrix (IFM). Our previous work shows that the IFM is critical for tendon function, facilitating sliding between fascicles to allow tendons to stretch. This function is particularly important in energy storing tendons, which experience extremely high strains during exercise, and therefore require the capacity for considerable inter-fascicular sliding and recoil. This capacity is not required in positional tendons. Whilst we have previously described the quasi-static properties of the IFM, the fatigue resistance of the IFM in functionally distinct tendons remains unknown. We therefore tested the hypothesis that fascicles and IFM in the energy storing equine superficial digital flexor tendon (SDFT) are more fatigue resistant than those in the positional common digital extensor tendon (CDET). Fascicles and IFM from both tendon types were subjected to cyclic fatigue testing until failure, and mechanical properties were calculated. The results demonstrated that both fascicles and IFM from the energy storing SDFT were able to resist a greater number of cycles before failure than those from the positional CDET. Further, SDFT fascicles and IFM exhibited less hysteresis over the course of testing than their counterparts in the CDET. This is the first study to assess the fatigue resistance of the IFM, demonstrating that IFM has a functional role within tendon and contributes significantly to tendon mechanical properties. These data provide important advances into fully characterising tendon structure-function relationships