Change of Bone Mechanical Strength in Rats after Spinal Cord Injury over a Short Term

This study investigated the time-course of changes in bone mechanical strength in rats with spinal cord injury (SCI). Sixty-four male Wistar rats underwent spinal cord transection at the thoracic nerve. Control rats underwent a sham procedure (SHAM). Animals were sacrificed at day 1, 4, 7 and 14 after operation. The mechanical strength of the left femur and tibia was measured by the three-point bending strength test. The bones were dried, weighed and burned to ash. A specimen of right tibia was prepared and examined under a microscope. Bone mechanical strength, dry bone weight, and ash content of the femur and tibia in SCI rats were significantly lower than those in SHAM animals. Dry bone weight and ash content began to decrease from the 4th day after SCI and reached their lowest at day 7 after operation. Bone mechanical strength had reduced significantly by the 14th day. Gaps and spaces were observed in the trabecular area at the same time. After SCI, calcified cartilage decreased and the reduction of bone mass occurred rapidly. Moreover, a decline of bone mechanical strength is caused within 2 weeks. Thus, SCI led to the atrophy of bone and caused the reduction of mechanical strength at an early stage. It is thus necessary to prevent bone loss after SCI immediately

Circular Dichroism in Cu Resonant Auger Electron Diffraction

Upon a core level excitation by circularly polarized light (CPL), the angular momentum of light, i.e. helicity, is transferred to the emitted photoelectron. This phenomenon can be confirmed by the parallax shift measurement of the forward focusing peak (FFP) direction in a stereograph of the atomic arrangement. The angular momentum of the emitted photoelectron is the sum of CPL helicity and the magnetic quantum number (MQN) of the initial state that define the quantum number of the core hole final state. The core hole may decay via Auger electron emission, where in this two electron process the angular momentum has to be conserved as well. Starting from a given core hole, different Auger decay channels with different final state energies and angular momenta of the emitted Auger electrons may be populated. Here we report the observation and formulation of the angular momentum transfer of light to Auger electrons, instead of photoelectrons. We measured photoelectron and Auger electron intensity angular distributions from Cu(111) and Cu(001) surfaces as a function of photon energy and photoelectron kinetic energy. By combining Auger electron spectroscopy with the FFP shift measurements at absorption threshold, element- and MQN-specific hole states can be generated in the valence band

Inhibition of Colorectal Cancer Tumorigenesis by Ursolic Acid and Doxorubicin Is Mediated by Targeting the Akt Signaling Pathway and Activating the Hippo Signaling Pathway

Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer subtype. Unsupervised classification of tumors based on protein expression profiles reveal three proteomic subclasses R1, R2, and R3. The R1 subclass is immunologically hot and demonstrated a good prognosis. R2 contains advanced proliferative tumor with TP53 mutations, high expression of VEGF receptor 2 and the worst prognosis. R3 is enriched with CTNNB1 mutations and elevated mTOR signaling pathway activity. Twenty-two proteins, including CDK1 and CDKN2A, are identified as potential prognostic markers. The proteomic classification presented in this study can help guide therapeutic decision making for liver cancer treatment

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells

New Detection Systems of Bacteria Using Highly Selective Media Designed by SMART: Selective Medium-Design Algorithm Restricted by Two Constraints

Culturing is an indispensable technique in microbiological research, and culturing with selective media has played a crucial role in the detection of pathogenic microorganisms and the isolation of commercially useful microorganisms from environmental samples. Although numerous selective media have been developed in empirical studies, unintended microorganisms often grow on such media probably due to the enormous numbers of microorganisms in the environment. Here, we present a novel strategy for designing highly selective media based on two selective agents, a carbon source and antimicrobials. We named our strategy SMART for highly Selective Medium-design Algorithm Restricted by Two constraints. To test whether the SMART method is applicable to a wide range of microorganisms, we developed selective media for Burkholderia glumae, Acidovorax avenae, Pectobacterium carotovorum, Ralstonia solanacearum, and Xanthomonas campestris. The series of media developed by SMART specifically allowed growth of the targeted bacteria. Because these selective media exhibited high specificity for growth of the target bacteria compared to established selective media, we applied three notable detection technologies: paper-based, flow cytometry-based, and color change-based detection systems for target bacteria species. SMART facilitates not only the development of novel techniques for detecting specific bacteria, but also our understanding of the ecology and epidemiology of the targeted bacteria

リガク リョウホウガク キョウイク ニ オケル キャッカンテキ リンショウ ノウリョク シケン OSCE ドウニュウ ノ カダイ ト ジッセン

The objective structured clinical examination (OSCE) is an examination format to assess the clinical competence ofhealth science students. The purpose of the present study was to survey the status of the implementation of an OSCE forundergraduate physical therapy students in Japanese universities and to introduce a physical therapy OSCE to the educationalprogram of our department based on the survey. Prior to making a questionnaire to survey the status of the implementation ofan OSCE, we visited two departments implementing an OSCE in the physical therapy educational program, and consolidatedthe information regarding the usage of OSCE. Subsequently, a questionnaire was sent to all physical therapy departments inJapanese universities. The questionnaire was answered by 53 % departments. The 64 % departments implemented physicaltherapy OSCE in their educational programs. The survey elucidated that the objective of the OSCE was to motivate studentsto improve clinical skill rather than to strictly assess the clinical competence, indicating that most departments used OSCE as ateaching OSCE. Actually, the students failed to go up to next grade due to the poor results of OSCE only in 19% departments.Only 14 % departments recruited outside standardized patients in the OSCE. In reference to the survey, we introduced theOSCE to our educational program as a teaching OSCE which facilitate student to learn clinical skill and adapt the studentsto a clinical circumstance. This study firstly reported the status of the implementation of an OSCE in Japanese four-yearundergraduate program, which could contribute to the standardization of the OSCE format in Japanese physical therapyeducation based on multicenter works among the departments