Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Comparison between Bipolar Hemiarthroplasty and Total Hip Arthroplasty for Unstable Intertrochanteric Fractures in Elderly Osteoporotic Patients

The present study was conducted to compare bipolar hemiarthroplasty (BA) with total hip arthroplasty (THA) in treatment of unstable intertrochanteric fractures in elderly osteoporotic patients. The THA group included 14 males and 26 females with a mean age of 73.4 years, and the BA group included 27 males and 45 females with a mean age of 76.5 years. Significant difference existed between the two groups in operation time, blood loss, transfusion volume and cost of hospitalization, while no remarkable difference was identified in hospitalization period, general complications, joint function, pain, rate of revision and mortality. No dislocation was observed in BA group while 3 occurred in THA group. The results indicated that for unstable intertrochanteric fractures in elderly osteoporotic patients, BA seems to be a better or more reasonable choice compared with THA for the reason of less blood loss, shorter operation time, lower cost and no dislocation

High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis.

BACKGROUND: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. RESULTS: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. CONCLUSIONS: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis

High levels of tumor-associated neutrophils are associated with improved overall survival in patients with stage II colorectal cancer.

Conflicting reports regarding whether high tumor-associated neutrophils (TAN) are associated with outcomes in colorectal cancer (CRC) exist. Previous investigators have counted TAN using non-neutrophil-specific immunohistochemistry (IHC) stains. We examined whether TAN levels as determined by multi-field manual counting would predict prognosis. IRB approval was obtained and two pathologists, blinded to stage/outcome, counted TAN in 20 high power fields (HPF) per specimen. TAN score was defined as the mean of these counts. High TAN was defined as at or greater than the median score for that stage. Demographics, tumor characteristics, and overall survival (OS) were obtained from the records and examined for association with TAN score. IHC for arginase expression was performed in a subset of samples. 221 patients were included. Stage II patients with high TAN scores had an OS of 232 months as compared to those with low TAN (OS = 85 months, p = 0.03). The survival benefit persisted in multivariable analysis (HR 0.48, CI 0.25-0.91, p = 0.026) controlling for age and sex. Women had increased survival as compared to men, and there were no significant prognostic associations with TAN count in stage III/IV patients, although there were only 12 stage IV patients. Arginase staining did not provide additional information. Stage II colorectal cancer patients with high TAN live nearly 3 times longer than those with low TAN. Women with stage II disease and high TAN counts appear to be driving the survival benefit seen in the stage II patients and have increased overall survival in all stages