A simple formula based on linear response theory is proposed to explain and predict the structural change of proteins upon ligand binding. By regarding ligand binding as an external perturbation, the structural change as a response is described by atomic fluctuations in the ligand-free form and the protein-ligand interactions. The results for three protein systems of various sizes are consistent with the observations in the crystal structures, confirming the validity of the linear relationship between the equilibrium fluctuations and the structural change upon ligand binding.

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Ectopic gastric mucosa in the upper esophagus is easily demonstrated at routine examination of the upper GI tract. Diagnosis can be based on location and characteristic radiographic appearance.

The disruption of the tumor microenvironment (TME) is a promising anti-cancer strategy, but its effective targeting for solid tumors remains unknown. Here, we investigated the anti-cancer activity of the mitochondrial complex I inhibitor intervenolin (ITV), which modulates the TME independent of energy depletion. By modulating lactate metabolism, ITV induced the concomitant acidification of the intra-and extracellular environment, which synergistically suppressed S6K1 activity in cancer cells through protein phosphatase-2A-mediated dephosphorylation via G-protein-coupled receptor(s). Other complex I inhibitors including metformin and rotenone were also found to exert the same effect through an energy depletion-independent manner as ITV. In mouse and patient-derived xenograft models, ITV was found to suppress tumor growth and its mode of action was further confirmed. The TME is usually acidic owing to glycolytic cancer cell metabolism, and this condition is more susceptible to complex I inhibitors. Thus, we have demonstrated a potential treatment strategy for solid tumors.

Introduction The purpose of the present study was to determine, in a mid-term follow-up 5 years or more after surgery, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and expiratory flow in patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion (PSF) with or without thoracoplasty. Methods The subjects were 134 patients with AIS who underwent PSF between 2004 and 2013. Forty-five patients agreed to participate in the study. We divided the patients into two groups as follows: 24 patients who underwent PSF with thoracoplasty from 2004 to 2010 in the TP group and 21 patients who underwent PSF without thoracoplasty from 2011 to 2013 in the non-TP group. We evaluated whole spine X-ray imaging and pulmonary function tests (PFTs) in these patients. PFTs measured FVC, FEV1, peak expiratory flow (PEF), maximum expiratory flow at 50% FVC (V50), maximum expiratory flow at 25% FVC (V25), and the ratio of V50 to V25 (V50/V25). Results The main thoracic curves were 53.6 ± 10.1° before surgery, 19.8 ± 7.6° 1 week after surgery, 22.3 ± 8.3° 2 years after surgery, and 23.3 ± 7.6° at the most recent observation. Compared with preoperative values, FVC, FEV1, and % FEV1 were improved significantly at the most recent observation. No significant difference was observed between % FVC before surgery and at the most recent observation. Compared with preoperative values, PEF, V50, and V25 were improved significantly at the most recent observation. V50/V25 did not change significantly. The changes in PFT values in the TP group and the non-TP group were compared. No significant differences were observed in FVC, % FVC, FEV1, % FEV1, PEF, V50, or V25. Conclusions Regardless of whether thoracoplasty was performed or not, FVC, FEV1, and expiratory flow were improved 5 years or later after PSF.