Stability Studies of Domain 2 of Neural Cadherin

Neural cadherin is a member of a family of calcium binding cell adhesion molecules. These cell surface proteins mediate intercellular adhesion through association of protomers on the same cell surface to form lateral interactions, and juxtaposed cells then undergo adhesive interaction. This action occurs by ordered calcium dependent associations mediated through the five extracellular N-terminus β-barrel domains. While the critical function and structure of classic cadherin is well established, the energetic mechanism of adhesion is still unclear. This study includes experiments into the purification and stability of Domain 2 in neural cadherin with the motivation that Domain 2 is a representative domain for this family of proteins. The definition of a domain boundary is somewhat arbitrary, and hence it was important to examine the effect of the adjoining linker regions that connect Domain 2 to the adjacent domains. The studies presented here employ purification and energetic analysis of two constructs, the neural cadherin Domain 2 (NCAD2) and the domain with both linkers at the N- and C-termini (L1-NCAD2-L2). Temperature denaturation experiments were performed on these protein segments to gain insight on the effect of linkers on the core domain. Several trends between Domain 2 of neural and epithelial cadherin are evident from the resulting data and provide a paradigm of characteristics for defining Domain 2 in the classical cadherin family. Like ECAD2, the linker segments destabilize the core domain in the absence of calcium, but the destabilization of L1-NCAD2-L2 can be fully reversed by the addition of calcium. Sodium chloride steadily increases the stability of both constructs, indicating that the destabilization of the core domain in the presence of linkers is due to the electrostatic repulsion between those additional residues. Thus, the context of Domain 2 of classical cadherins within the whole protein affects its thermodynamic characteristics

The influence of community factors on the engagement of residents in place promotion: Empirical evidence from an Italian heritage site

The engagement of community residents in place promotion is increasingly recognized as desirable for ensuring effective and reliable communication with tourists. The study investigated the effects of community factors on residents' engagement in the promotion of an Italian heritage site. Community commitment, environmental attitudes, and perceptions of the effectiveness of existing place marketing communications were found to be decisive in influencing residents' engagement in the promotion of the Amalfi Coast. The paper helps to shed light on collaboration in place promotion, thus enriching the debate on the ambassadorship role of residents and suggesting useful insights for policy makers/destination management organization

Treatment of chordomas with CyberKnife: georgetown university experience and treatment recommendations.

OBJECTIVE: To determine the efficacy and safety of chordoma treatment with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (CK/SRS). METHODS: Eighteen patients with chordoma were treated with CK/SRS as a primary adjuvant (17 patients) or the only treatment (1 patient). The series included 24 lesions (28 treatments). The median age of the patients was 60 years (range, 24-85 years). Forty-four percent of the tumors were located in the mobile spine, 39% inside the cranium, and 17% in the sacral region. The male-to-female ratio was 1:1. The mean tumor volume was 128.0 mL (range, 12.0-457.3 mL), and the median dose of 35 Gy (range, 24.0-40.0 Gy) was delivered in 5 sessions. The median follow-up period was 46 months (range, 7-65 months). RESULTS: There were 3 significant complications in patients with previous irradiation, including infection in the surgical/radiation site (2 patients) and decreased vision (1 patient). Improvement in pain and quality of life did not reach statistical significance (alpha = 0.05). Seven patients experienced recurrence at a median of 10 months (range, 5-38 months), and 4 patients with disseminated disease died 7 to 48 months after therapy. Two patients had a partial response, whereas 9 others had stable disease. The local control rate at 65 months was 59.1%, with an overall survival of 74.3% and disease-specific survival of 88.9%. We estimated an alpha/beta ratio of 2.45 for chordomas, which supports hypofractionation. CONCLUSION: The CK/SRS safety and efficacy profile compares favorably with those of other treatment delivery systems. CK/SRS appears to reduce tumor volume, given an adequate dose. The authors recommend treatment with 40 Gy in 5 sessions to the clinical treatment volume, which includes the gross tumor volume and at least a 1-cm margin

Brachytherapy improves outcomes in young men (≤60 years) with prostate cancer: A SEER analysis

PURPOSE—The aim of the study was to compare prostate cancer–specific mortality (PCSM) in young men with clinically localized prostate cancer treated by either external beam radiation (EBRT) alone or brachytherapy with or without external beam radiation. METHODS AND MATERIALS—Utilizing the Surveillance, Epidemiology and End Results database, 15,505 patients ≤60 years of age diagnosed with prostate cancer between 2004 and 2009 and treated with radiation therapy alone were identified. Incidence of PCSM was determined for both groups and compared using competing risk models. RESULTS—The overall 8-year PCSM for the study population was 1.9% (95% confidence interval [CI]: 1.6–2.2). For patients treated with EBRT or brachytherapy with or without external beam, the 8-year PCSM was found to be 2.8% (CI: 2.2–3.4) and 1.2% (CI: 0.9–1.6), respectively (p \u3c 0.001). Univariable analysis demonstrated that brachytherapy was associated with lower PCSM risk (hazard ratio = 0.40; CI: 0.30–0.54; p \u3c 0.001). High Gleason risk category, black race, higher Tumor (T) stage, and higher grade were all associated with greater mortality risk (p \u3c 0.01). On multivariable analysis, brachytherapy continued to be associated with a significantly lower mortality risk (hazard ratio = 0.65; CI: 0.47–0.89;p = 0.008). Subgroup analyses found that among those with Gleason score ≥8, younger patients had increased risk of PCSM (p = 0.001). CONCLUSIONS—In men ≤60 years of age with prostate cancer, radiation therapy continues to offer excellent outcomes. After adjusting for relevant variables, the use of brachytherapy was associated with reduced PCSM compared to treatment with EBRT alone

A Review of the Evidence for the Use of Ventilation as a Surrogate Measure of Energy Expenditure

International audienceAbstract Precise measurement of sedentary behavior and physical activity is necessary to characterize the dose-response relationship between these variables and health outcomes. The most frequently used methods employ portable devices to measure mechanical or physiological parameters (eg, pedometers, heart rate monitors, accelerometers). There is considerable variability in the accuracy of total energy expenditure (TEE) estimates from these devices. This review examines the potential of measurement of ventilation (VE) to provide an estimate of free-living TEE. The existence of a linear relationship between VE and energy expenditure (EE) was demonstrated in the mid-20th century. However, few studies have investigated this parameter as an estimate of EE due to the cumbersome equipment required to measure VE. Portable systems that measure VE without the use of a mouthpiece have existed for about 20 years (respiratory inductive plethysmography). However, these devices are adapted for clinical monitoring and are too cumbersome to be used in conditions of daily life. Technological innovations of recent years (small electromagnetic coils glued on the chest/back) suggest that VE could be estimated from variations in rib cage and abdominal distances. This method of TEE estimation is based on the development of individual/group calibration curves to predict the relationship between ventilation and oxygen consumption. The new method provides a reasonably accurate estimate of TEE in different free-living conditions such as sitting, standingand walking. Further work is required to integrate these electromagnetic coils into a jacket or T-shirt to create a wearable device suitable for long-term use in free-living conditions