The pathological complete response and secreted protein acidic and rich in cysteine expression in patients with breast cancer receiving neoadjuvant nab-paclitaxel chemotherapy

学位記番号：医博甲178

Opposing role of condensin hinge against replication protein A in mitosis and interphase through promoting DNA annealing

Condensin is required for chromosome dynamics and diverse DNA metabolism. How condensin works, however, is not well understood. Condensin contains two structural maintenance of chromosomes (SMC) subunits with the terminal globular domains connected to coiled-coil that is interrupted by the central hinge. Heterotrimeric non-SMC subunits regulate SMC. We identified a novel fission yeast SMC hinge mutant, cut14-Y1, which displayed defects in DNA damage repair and chromosome segregation. It contains an amino acid substitution at a conserved hinge residue of Cut14/SMC2, resulting in diminished DNA binding and annealing. A replication protein A mutant, ssb1-418, greatly alleviated the repair and mitotic defects of cut14-Y1. Ssb1 protein formed nucleolar foci in cut14-Y1 cells, but the number of foci was diminished in cut14-Y1 ssb1-418 double mutants. Consistent with the above results, Ssb1 protein bound to single-strand DNA was removed by condensin or the SMC dimer through DNA reannealing in vitro. Similarly, RNA hybridized to DNA may be removed by the SMC dimer. Thus, condensin may wind up DNA strands to unload chromosomal components after DNA repair and prior to mitosis. We show that 16 suppressor mutations of cut14-Y1 were all mapped within the hinge domain, which surrounded the original L543 mutation site

Comparative Study of Multicanonical and Simulated Annealing Algorithms in the Protein Folding Problem

We compare a few variants of the recently proposed multicanonical method with the well known simulated annealing for the effectiveness in search of the energy global minimum of a biomolecular system. For this we study in detail Met-enkephalin, one of the simplest peptides. We show that the new method not only outperforms simulated annealing in the search of the energy groundstate but also provides more statistical-mechanical information about the system.Comment: to be published in Physica A, LATEX 32 pages, figures available on reques

The Maintenance of Lymphatic Vessels in the Cornea Is Dependent on the Presence of Macrophages

Purpose.: It has been shown previously that the presence in the cornea of antigen-presenting cells (APC), such as macrophages (MPS) and lymphangiogenesis, is a risk for corneal transplantation. We sought to determine whether the existence of lymphatic vessels in the non-inflamed cornea is associated with the presence of MPS. Methods.: Flat mounts were prepared from corneas of untreated C57BL/6, CD11b−/−, F4/80−/−, and BALB/c mice, and after suture placement or corneal transplantation, observed by immunofluorescence for the presence of lymphatic vessels using LYVE-1 as a marker of lymphatic endothelium. Innate immune cells were detected in normal mouse corneas using CD11b, F4/80, CD40, as well as MHC-class II. Digital images of the flat mounts were taken using a spot image analysis system, and the area covered by lymphatic vessels was measured using NIH Image software. Results.: The number of spontaneous lymphatic vessels in C57BL/6 corneas was significantly greater than in BALB/c corneas (P = 0.03). There were more CD11b+ (P < 0.01) and CD40+, MHC-class II (+) cells in the C57BL/6 corneas than in BALB/c mouse corneas. MPS depletion via clodronate liposome in C57BL/6 mice led to fewer spontaneous lymphatic vessels and reduced inflammation-induced lymphangiogenesis relative to control mice. Mice deficient in CD11b or F4/80 had fewer spontaneous lymphatic vessels and less lymphangiogenesis than control C57BL/6 mice. Conclusions.: C57BL/6 mouse corneas have more endogenous CD11b+ cells and lymphatic vessels. The endogenous lymphatic vessels, along with pro-inflammatory MPS, account for the high risk of corneal graft rejection in C57BL/6 mice. CD11b+ and F4/80+ MPS appear to have an important role in of the formation of new lymphatic vessels

Basic assessment on adding platelet measurement to legal health checkup in Japan: A cross-sectional and 20-year longitudinal study

BackgroundIn Japan, health checkups for workers are legally compulsory. Considering legal health checkup items are important for Japanese workers' health problems. To date, the legal health checkup items for blood cell counts include only red blood cell counts and hemoglobin but not platelet counts. This study aimed to investigate the significance of measuring platelets in workers by showing the association between the FIB-4 index (FIB-4), which can be easily calculated from factors including platelet counts and viral hepatitis infection.MethodBoth cross-sectional and longitudinal analyses were conducted on the comprehensive medical examinations of male workers. In fiscal year (FY) 2019, a logistic regression model was applied to 12,918 examinees. For 13,459 examinees (mean age = 47.5 ± 9.3 SD), FY2000 was set to be followed until FY2019. A total of 149,956 records between FY2000 and FY2019 were analyzed cross-sectionally, and 8,038 men who were consecutively examined to FY2019 at the longest were analyzed longitudinally. Receiver operating characteristic (ROC) curve–area under the ROC curve (ROC–AUC) and Cox proportional methods were used to examine the association between platelet-related indices and viral hepatitis infection.ResultsLogistic regression showed that the risk of FIB-4 ≥ 2.67 was mostly associated with hepatitis C virus antibody (HCVAb) positivity [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.08–5.86], while negatively associated with body mass index (BMI) (OR = 0.54, 95% CI = 0.30–0.97), and not associated with the presence of fatty liver. To detect HVC Ab positivity, ROC–AUC showed more effectiveness in FIB-4 than in the AST/ALT ratio (0.776, 95% CI = 0.747–0.773 vs. 0.552; 95% CI = 0.543–0.561). The Cox analysis showed that the risk of FIB-4 ≥ 2.67 was closely associated with hepatitis B virus surface antigen (HBsAg) [hazard ratio (HR) = 3.1, 95% CI = 2.0–4.6] and HCV Ab positivity (HR = 3.2, 95% CI = 2.0–5.0).ConclusionOur results suggest that it might be worth considering that usage of information on platelets in legal health checkups could be some help not to overlook workers with hepatitis virus carriers as a complementary countermeasure, although further investigations are needed into its practical application