RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
Acid Phosphatase ; Animals ; Asian Continental Ancestry Group ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption ; Femur ; Humans ; Mice ; Mice, Transgenic ; Osteitis Deformans* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Tacrolimus Binding Proteins ; Transcription Factors

Objective To explore the impacts of WeChat on transitional nursing in patients with coronary heart disease and interventional therapy. Methods A total of 80 coronary heart disease patients received interventional therapy were selected and randomly divided into observation group and control group, with each group 40 cases. The patients of control group were given routine health education, while the patients of observation group were given transitional nursing by WeChat public account and chat group. We compared the results of SAS and SDS, compliance of taking medicine and rehabilitation, and ADL scores between two groups when patients came back hospital for reexamination at three months after discharge. Results At reexamination, the scores of SAS, SDS and ADL in observation group were (42. 50 ± 5. 08), (40. 71 ± 5. 85), (85. 33 ± 11. 12) better than those of the control group (t=2. 342, 2. 593, 2. 456;P=0. 019, 0. 009, 0. 016); the compliance oftaking medication and rehabilitation excises were (17. 69 ± 3. 03), (51. 30 ± 1. 28) which were statistical significant better than scores of the control group (t=2. 325, 3. 028;P=0. 021, 0. 003). Conclusions WeChat has positive impacts on transitional nursing in patients with coronary heart disease and interventional therapy. It can improve patient′s self-care ability, reduce negative emotion, and improve the compliance of taking medicine and physical exercise rehabilitation, which is worthy of promotion.

Objective To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic testing in a large family. Methods PCR was performed to amplify the coding region of androgen gene, followed by direct sequencing in the patients with CAIS and relatives in this family. Results A missense mutation Arg773His was identified in the patients (homozygous) and carriers(heterozygous). Conclusions Mutation Arg773His in the AR gene leads to CAIS in this family. Molecular genetic testing of CAIS facilitates not only prenatal genetic diagnosis but also preimplantation genetic diagnosis and offers genetic counseling for future pregnancies to abandon the transmission of the mutated X chromosome to the coming generation.

The pyramidal angles of 102 cases (204 sides) of Chinese adult crania were studied.The coefficient of correlation between the average figures of the cranial length and pyramidal angles were calculated. The coefficient of correlation between the cranial length and the pyramidal angle is -0.288 and between the difference of cranial length and breadth and the pyramidal angle is -0.326, which denote a rather high degree of negative correlation. It is concluded that the maximum length is inversely proportional to the size of the pyramidal angle, that is, the greater the length, the less the angle and vice versa.The mean value of the pyramidal angles is 52? (more exactly, 51.635?) in Chinese. The angles on both sides are nearly equal in 46.6% of cases, and are apparently different in 53.4% of cases. Its sex and side differences are insignificant.The authors calculated the regression formulae of the estimation of pyramidal angle from cranial length and from the difference between its length and breadth. The results of the estimation of regression formulae suggest that by taking the cranial length as 17 cm or their difference as 3 cm and the pyramidal angle as 52? to be the basic key values and if the cranial length or their difference increases by 1 cm, the pyramidal angle will decrease by 1 degree and inversely it is also true.