Small Oscillatory Accelerations, Independent of Matrix Deformations, Increase Osteoblast Activity and Enhance Bone Morphology

A range of tissues have the capacity to adapt to mechanical challenges, an attribute presumed to be regulated through deformation of the cell and/or surrounding matrix. In contrast, it is shown here that extremely small oscillatory accelerations, applied as unconstrained motion and inducing negligible deformation, serve as an anabolic stimulus to osteoblasts in vivo. Habitual background loading was removed from the tibiae of 18 female adult mice by hindlimb-unloading. For 20 min/d, 5 d/wk, the left tibia of each mouse was subjected to oscillatory 0.6 g accelerations at 45 Hz while the right tibia served as control. Sham-loaded (n = 9) and normal age-matched control (n = 18) mice provided additional comparisons. Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls. Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (−6%) and structural model index (−11%). These in vivo data indicate that mechanosensory elements of resident bone cell populations can perceive and respond to acceleratory signals, and point to an efficient means of introducing intense physical signals into a biologic system without putting the matrix at risk of overloading. In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism

Measurement of jet-substructure observables in top quark, W boson and light jet production in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of jet substructure observables is presented using data collected in 2016 by the ATLAS experiment at the LHC with proton-proton collisions at s√ = 13 TeV. Large-radius jets groomed with the trimming and soft-drop algorithms are studied. Dedicated event selections are used to study jets produced by light quarks or gluons, and hadronically decaying top quarks and W bosons. The observables measured are sensitive to substructure, and therefore are typically used for tagging large-radius jets from boosted massive particles. These include the energy correlation functions and the N-subjettiness variables. The number of subjets and the Les Houches angularity are also considered. The distributions of the substructure variables, corrected for detector effects, are compared to the predictions of various Monte Carlo event generators. They are also compared between the large-radius jets originating from light quarks or gluons, and hadronically decaying top quarks and W bosons

Relationship between HPV and the biomarkers annexin A1 and p53 in oropharyngeal cancer

BACKGROUND: Human papillomavirus (HPV) is often present in oropharyngeal cancers. Head and neck tumors have been examined for other molecular markers including p53 and annexin A1 (ANXA1). Here, we investigated the prevalence of HPV and its relationship with p53 and ANXA1 in patients with oropharyngeal cancer. METHODS: We have analyzed tumor and adjacent mucosa from 22 patients with squamous cell carcinoma of the oropharynx in addition to samples of the oropharyngeal epithelium in subjects without cancer. We evaluated the presence of the HPV (subtypes 16/18 and 31/33) by chromogenic in situ hybridization. Additionally, we used immunofluorescence to examine the expression of p16, p53, ANXA1 and the phosphorylation of the ANXA1 residues Ser27 (ANXA1-SER) and Tyr21 (ANXA1-TYR). RESULTS: We have detected the presence of HPV genome in 59% of the 22 tumors. Of those, 92% were also positive for p16 immunostaining. Furthermore, we demonstrated a reduction in the expression of p53 in HPV + compared to HPV- tumors. Also, a reduction was observed in the expression of ANXA1 in tumors compared to epithelium from the margins and from controls. We also noted a reduction in ANXA1-TYR in tumors. However, the expression of both ANXA1 and ANXA1-SER were elevated in the margins of the HPV + versus HPV- tumors. CONCLUSIONS: Our results confirm a high prevalence of HPV in oropharyngeal cancer and a reduction in p53 expression in HPV + tumors. We observed a hypoexpression of ANXA1 and ANXA1-TYR in oropharyngeal cancer. The increase in ANXA1-SER in the margins of HPV + tumors suggests that the epithelium in these cases had been activated by an infectious agent. Those findings indicate that ANXA1 and its phosphorylated forms can play important roles in the response to HPV infection and the carcinogenesis of the oropharynx