Fieldsshepherd8246

melanogaster. Although such effects have already been known in mammals, the current results suggest that the apoptosis may play a similar role in insects as well.We studied how mutation rates promote the evolution of advantageous traits in an asexual population. First, to examine the effects of mutation rates on the evolution of an advantageous trait (high competitive ability), we carried out simulation analyses with competition between individuals for survival. Second, to examine the mechanism underlying the promotion of advantageous trait evolution, we calculated the probabilities that new favorable effects of mutations on the phenotype were acquired and that existing favorable effects were maintained. In the simulation analyses, advantageous traits evolved in the population with a low mutation rate; however, when the mutation rate was extremely low, advantageous traits evolved slowly because few beneficial mutations occurred. Then, the numerical calculations showed that the probability of acquiring new favorable effects of mutations on the phenotype and the probability of maintaining existing favorable effects are high if the mutation rate is low. The former occurs because, if the mutation rate is high, multiple mutations may occur in a genome, and even if beneficial mutations occur, their favorable effects may be masked by simultaneously occurring deleterious mutations. However, if the mutation rate is low, it is likely that only one beneficial mutation occurs, and its favorable effect on the phenotype is direct. In conclusion, low mutation rates are advantageous because they promote favorable phenotypic effects of mutations without interference from deleterious mutations; these low rates not only prevent the occurrence of deleterious mutations but also help maintain existing beneficial mutations and promote the evolution of advantageous traits.BACKGROUND The fluoroscopic individualized LAO (i-LAO) projection has demonstrated high accuracy for identifying right ventricular (RV) lead positioning, likely by approximating a view along the septal or RV long axes. However, RV and septal anatomical axes have not been studied, and their relation with i-LAO is unknown. We sought to determine RV, septal, and left ventricular (LV) long-axis orientations by CT scan and to compare them to the i-LAO angle, to confirm the anatomical relevance of i-LAO. METHODS We prospectively included patients (pts) for whom i-LAO angle was determined during pacemaker or defibrillator implant. Then, RV, septal, and LV long-axis orientations were determined by CT scan by a physician blinded to i-LAO data. The horizontal components of the cardiac axes were compared with those of the i-LAO angle. RESULTS We included 26 pts. Median values were 57.5° for i-LAO angle (range 47.5-70), 64.5° for RV axis (range 48-90), 51.5° for septal axis (range 39-74), and 37° for LV axis (range 25-67). i-LAO angle best correlated with septal axis (r = 0.91 and ρc = 0.71). Up to an angle of 70° (maximal measurable i-LAO value; 23/26 pts), the i-LAO angle was comprised between the septal and the RV axes (21/23 pts, 91.3%), or within 2° of this interval (2/23 pts, 8.7%). CONCLUSIONS RV and septal anatomical axes present major interindividual variations, prompting the use of individualized fluoroscopy criteria for lead implantation. i-LAO angle demonstrated to be almost constantly between the septal and RV long axes, thus confirming its anatomical relevance for RV lead implantation.The trimeric transmembrane collagen BP180, also known as collagen XVII, is an essential component of hemidesmosomes at the dermal-epidermal junction and connects the cytoplasmic keratin network to the extracellular basement membrane. Dysfunction of BP180 caused by mutations in patients with junctional epidermolysis bullosa or autoantibodies in those with bullous pemphigoid leads to severe skin blistering. The extracellular collagenous domain of BP180 participates in the protein's triple-helical folding, but the structure and functional importance of the intracellular domain (ICD) of BP180 are largely unknown. In the present study, we purified and characterized human BP180 ICD. When expressed in Escherichia coli as glutathione-S-transferase or 6 × histidine tagged fusion protein, the BP180 ICD was found to exist as a monomer. Analysis of the secondary structure content by circular dichroism spectroscopy revealed that the domain is intrinsically disordered. This finding aligned with that of a bioinformatic analysis, which predicted a disordered structure. Interestingly, both anionic detergent micelles and lipid vesicles induced partial folding of the BP180 ICD, suggesting that in its natural environment, the domain's folding and unfolding may be regulated by interaction with the cell membrane or accompanying proteins. We hypothesize that the intrinsically disordered structure of the ICD of BP180 contributes to the mechanism that allows the remodeling of hemidesmosome assembly.BACKGROUND Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p  less then  0.001). CONCLUSIONS The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. Glutathione In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.