Nonneutral evolution of volume fluctuations in lysozymes revealed by normal-mode analysis of compressibility

The evolution of structural fluctuations of proteins was examined by calculating the isothermal compressibility (beta(T)) values of chicken lysozyme and its six evolutionary mutants at Thr40, Ile55, and Ser91 (a ternary mutant corresponding to bobwhite lysozyme) from their X-ray structures by normal-mode analysis at 300 K. The Or values of the two extant lysozymes from chicken and bobwhite were 1.61 and 1.59 Mbar(-1), respectively, but five other evolutionary mutants showed larger beta(T) values of up to 2.17 Mbar(-1). These results suggest that ancestral lysozymes exhibit larger volume fluctuations than extant ones, and hence that the molecular evolution of lysozymes has followed a nonneutral evolutionary pathway. The evolutionary mutants contained large amount of cavities, although no change was visible in the X-ray structures. There was a linear correlation between beta(T) and total cavity volume, predicting that the cavity volume or atomic packing is an important factor regulating volume fluctuations during the molecular evolution of this protein. (C) 2011 Elsevier B.V. All rights reserved

Pressure-sensitive reaction yield of the TePixD blue-light sensor protein

The effect of pressure on the dissociation reaction of the TePixD decamer was investigated by high-pressure transient grating (TG). The TG signal intensity representing the dissociation reaction of the TePixD decamer significantly decreased by applying a relatively small pressure. On the other hand, the reaction rate increased with increasing pressure. The equilibrium between the pentamer and the decamer was investigated by high-pressure dynamic light scattering. The results indicated that the fraction of the decamer slightly increased in the high-pressure region. From these measurements, it was concluded that the pressure-dependent signal intensity originated from the decrease of the quantum yield of the dissociation reaction of the decamer, indicating that this reaction efficiency is very sensitive to pressure. Using densimetry at high pressures, the compressibility was found to be pressure dependent even in a relatively low pressure range. We attributed the origin of the pressure-sensitive reaction yield to the decrease of compressibility at high pressure. Because the compressibility is related to the volume fluctuation, this observation suggests that the driving force for this reaction is fluctuation of the protein. The relationship between the cavities at the interfaces of the monomer units and the reactivity is also discussed

Pressure dependence of the apparent specific volume of bovine serum albumin : Insight into the difference between isothermal and adiabatic compressibilities

There are some theoretical arguments related to interpreting the adiabatic compressibility (beta(s)) of a protein determined from the sound velocity and the difference between beta(s) and isothermal compressibility (beta(T)). To address these problems experimentally, we constructed a high-pressure oscillating densitometer and used it to measure the apparent specific volume of bovine serum albumin as a function of pressure (0.1-78 MPa) and temperature (5-35 degrees C). The beta(T) determined from plots of the apparent specific volume vs. pressure was slightly larger than beta(s) at all temperatures examined, with the difference between the two compressibilities increasing as the temperature was decreased. Only at room temperature did the observed beta(T) agree with those estimated from beta(s) using the heat capacity and the thermal expansibility of the protein, suggesting that there are significant as-yet-unknown mechanisms that affect protein compressibility

Alveolar echinococcosis of the liver in children

Background/purpose. Alveolar echinococcosis of the liver (AEL) is a zoonosis that is distributed in cold regions of the northern hemisphere. The disease is mostly found in adults and rarely in pediatric patients because it tends to be slow growing. Patients and methods. Ten Japanese pediatric patients with AEL (under fifteen-year-old) have been operated on in Hokkaido University Hospital from January 1936 to June 2008. We examined these children and revealed the characteristics of AEL. Results. The patients included three males and seven females whose mean age was 10.9 years old, ranging from 7 to 15. The length of follow-up was from 3 months to 33 years (median: 19 years). Six cases were picked up by mass screening and nine cases who underwent hepatectomy are still alive and one case whose tumors were unresectable died of liver failure. Conclusion. Our cases indicate that some AEL pediatric patients advanced rapidly, so early detection is imperative. Thus, screening examinations are essential for children in contaminated areas, and complete radical resection should be performed if a liver tumor is found on a screening examination and diagnosed as AEL

Persistent Urinary Incontinence After Nephrectomy: A Case of Inverted-Y Ureteral Duplication with Ectopic Ureteral Insertion into the Vagina

Inverted-Y ureteral duplication is one of the rarest anomalies of ureteral branching. We encountered a 20-year-old female patient with persistent incontinence even after nephrectomy for ectopic ureteral insertion into the vagina. She had inverted-Y ureteral duplication between the bladder and vagina, and urine was being transported from the bladder to the vagina. To the best of our knowledge, this is a rare case of inverted-Y ureteral duplication with ectopic ureteral insertion into the vagina as well as the ureter into the bladder, which became apparent due to persistent urinary incontinence even after nephrectomy

Preoperative chemotherapy in colorectal cancer patients with synchronous liver metastasis

The response to preoperative chemotherapy is useful for predicting prognosis in unresectable and resectable disease. However, the prognostic benefit of chemotherapy prior to hepatectomy in patients with colorectal carcinoma and resectable or marginally resectable liver metastases remains unclear. The present study investigated the effect of preoperative chemotherapy on the prognosis of patients with colorectal cancer and resectable or marginally resectable synchronous liver metastasis. A total of 106 patients were retrospectively reviewed, who underwent hepatectomy for colorectal metastasis. The prognosis of 64 patients who received neoadjuvant chemotherapy (NAC) were compared with the 42 patients who did not (non-NAC). Furthermore, a total of 43 patients who responded to chemotherapy were compared with the 21 who did not. Preoperative chemotherapy was administered for 5.7 months, wherein 50 patients (78%) received a single regimen, and 54 (84%) received oxaliplatin. There were more patients with <3 metastases and maximum diameters <5 cm in the non-NAC group. The median survival time was 86.0 and 71.6 months in the NAC and non-NAC groups, respectively (P=0.33). Subgroup analysis on the basis of tumor size and number showed no prognostic differences between the two groups. The median survival time was longer in responders than in non-responders (85 vs. 56 months; P=0.01). However, the median relapse-free survival was equivalent in both groups (16.4 and 10.7 months). Preoperative chemotherapy did not prolong survival. Furthermore, it did not prevent recurrence, even in clinical responders. Therefore, it should not be routinely offered to patients with resectable liver metastasis before their hepatectomy