Early development of the Amur sleeper (Perccottus glenii, Dybowski, 1877): a remarkable invasive species in Eurasia

To investigate the ontogeny of Perccottus glenii, embryonic, larval and juvenile development of P. glenii were examined under captive condition. The fertilized eggs with numerous oil droplets were orange-pink in color, prolate spherical in shape and had average length of 3.32±0.14 mm and width of 1.24±0.04 mm. From fertilization to hatching, the ontogenesis of the fish spent more than 200 h, and the process of embryonic development was divided into 25 stages based on the morphological characteristics. The newly hatched larvae, with well-developed swim bladder and pectoral fins, measured 5.07±0.18mm in total length. Initial feeding occurred at day 2 after hatching (AH) and the complete absorption of yolk sphere was observed 3 days after hatching. At day 40 AH, scales and vertical pigment were found to be appear. Scales covered the entire body and all fins were well developed 70 days AH, at which time the juveniles reached the young stage with a total length (TL) of 24.74±4.28 mm. At day 140 AH, The fry with a TL of 29.57±4.65 mm, were morphologically similar to the adults except for size

p53 Binds to and Is Required for the Repression of Arf Tumor Suppressor by HDAC and Polycomb

The expression of tumor suppressor Arf is tightly repressed during normal cell growth at a young age, and is activated by oncogenic insults and during aging, resulting in p53 activation and cell cycle arrest to prevent hyperproliferation. The mechanisms of both transcriptional repression and activation of Arf are not understood. We show that p53 binds to and represses Arf expression and that this repression requires the function of both histone deacetylase (HDAC) and polycomb group (PcG) proteins. Inactivation of p53 leads to increased Arf transcription in both mouse embryonic fibroblasts (MEFs) cultured in vitro and in tissues and organs of p53 null mice. Activation of endogenous p53 enhances Arf repression, and reintroduction of p53 back into p53 null MEFs restores Arf repression. Both DNA binding and trans-activation activities of p53 are required for Arf repression. We show that p53 is required for both HDAC and PcG to repress Arf expression. Bindings of both HDAC and PcG to Arf are disrupted by inactivation of p53 and can be restored in p53 null MEFs by the reintroduction of wild-type, but not mutant, p53. These results indicate that p53 recruits both HDAC and PcG to Arf locus to repress its expression, and this repression constitutes a second feedback loop in p53 regulation

Cytoplasmic CUL9/PARC Ubiquitin Ligase Is a Tumor Suppressor and Promotes p53-Dependent Apoptosis

A wide range of cell stresses, including DNA damage, signal to p53 through post-translational modification of p53. The cytoplasmic functions of p53 are emerging as an important constituent of p53’s role in tumor suppression. Here we report that deletion of the Cul9 (formerly Parc) gene, which encodes an E3 ubiquitin ligase that binds to p53 and localizes in the cytoplasm, resulted in spontaneous tumor development, accelerated Eμ-Myc-induced lymphomagenesis and rendered mice susceptible to carcinogenesis. Cul9-p53 double mutant mice exhibited indistinguishable tumor phenotypes as p53 single mutant mice, indicating that the function of Cul9 in tumor suppression is largely mediated by p53. Deletion of Cul9 had no significant effect on cell cycle progression, but attenuated DNA damage-induced apoptosis. Ectopic expression of wild-type CUL9, but not a point mutant CUL9 deficient in p53 binding, promotes apoptosis. These results demonstrate CUL9 as a potential p53 activating E3 ligase in the cytoplasm

Three-Dimensional Analysis of the Curvature of the Femoral Canal in 426 Chinese Femurs

. Purpose. The human femur has long been considered to have an anatomical anterior curvature in the sagittal plane. We established a new method to evaluate the femoral curvature in three-dimensional (3D) space and reveal its influencing factors in Chinese population. Methods. 3D models of 426 femurs and the medullary canal were constructed using Mimics software. We standardized the positions of all femurs using 3ds Max software. After measuring the anatomical parameters, including the radius of femoral curvature (RFC) and banking angle, of the femurs using the established femur-specific coordinate system, we analyzed and determined the relationships between the anatomical parameters of the femur and the general characteristics of the population. Results. Pearson's correlation analyses showed that there were positive correlations between the RFC and height ( = 0.339, < 0.001) and the femoral length and RFC ( = 0.369, < 0.001) and a negative correlation between the femoral length and banking angle ( = −0.223, < 0.001). Stepwise linear regression analyses showed that the most relevant factors for the RFC and banking angle were the femoral length and gender, respectively. Conclusions. This study concluded that the banking angle of the femur was significantly larger in female than in male

CUL9 Mediates the Functions of the 3M Complex and Ubiquitylates Survivin to Maintain Genome Integrity

The Cullin 9 (CUL9) gene encodes a putative E3 ligase that localizes in the cytoplasm. Cul9 null mice develop spontaneous tumors in multiple organs, however either the cellular or molecular mechanisms of CUL9 in tumor suppression are currently not known. We show here that deletion of Cul9 leads to abnormal nuclear morphology, increased DNA damage and aneuploidy. CUL9 knockdown rescues the microtubule and mitosis defects in cells depleted for CUL7 or OBSL1, two genes that are mutated in a mutually exclusive manner in 3M growth retardation syndrome and function in microtubule dynamics. CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7. Depletion of CUL7 decreases survivin level and overexpression of survivin rescues the defects caused by CUL7 depletion. We propose a 3M–CUL9-survivin pathway in maintaining microtubule and genome integrity, normal development and tumor suppression

Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes

Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes. Methods: We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph. Results: We found that the effects of the 18 POR SNPs on 10 CYP activities were CYP genotype-dependent. The POR mutations were significantly associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by these POR SNPs. Notably, the effect of a specific POR mutation on the activity of a CYP genotype could not be predicted from other CYP genotypes of even the same CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was uncovered, which was not necessarily consistent with the effect of either single POR SNP. Conclusions: The effects of POR SNPs on CYP activities were not only CYP-dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of a POR SNP alone and in combination with other POR SNPs (MSGP) was not always consistent, nor predictable. Understanding the impact of POR gene polymorphisms on drug metabolism necessitates knowing the complete SNP complement of POR and the genotype of the relevant CYPs