Ribosome binding protein GCN1 regulates the cell cycle and cell proliferation and is essential for the embryonic development of mice.

Amino acids exert many biological functions, serving as allosteric regulators and neurotransmitters, as constituents in proteins and as nutrients. GCN2-mediated phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) restores homeostasis in response to amino acid starvation (AAS) through the inhibition of the general translation and upregulation of amino acid biosynthetic enzymes and transporters by activating the translation of Gcn4 and ATF4 in yeast and mammals, respectively. GCN1 is a GCN2-binding protein that possesses an RWD binding domain (RWDBD) in its C-terminus. In yeast, Gcn1 is essential for Gcn2 activation by AAS; however, the roles of GCN1 in mammals need to be established. Here, we revealed a novel role of GCN1 that does not depend on AAS by generating two Gcn1 mutant mouse lines: Gcn1-knockout mice (Gcn1 KO mice (Gcn1-/-)) and RWDBD-deleted mutant mice (Gcn1ΔRWDBD mice). Both mutant mice showed growth retardation, which was not observed in the Gcn2 KO mice, such that the Gcn1 KO mice died at the intermediate stage of embryonic development because of severe growth retardation, while the Gcn1ΔRWDBD embryos showed mild growth retardation and died soon after birth, most likely due to respiratory failure. Extension of pregnancy by 24 h through the administration of progesterone to the pregnant mothers rescued the expression of differentiation markers in the lungs and prevented lethality of the Gcn1ΔRWDBD pups, indicating that perinatal lethality of the Gcn1ΔRWDBD embryos was due to simple growth retardation. Similar to the yeast Gcn2/Gcn1 system, AAS- or UV irradiation-induced elF2α phosphorylation was diminished in the Gcn1ΔRWDBD mouse embryonic fibroblasts (MEFs), suggesting that GCN1 RWDBD is responsible for GCN2 activity. In addition, we found reduced cell proliferation and G2/M arrest accompanying a decrease in Cdk1 and Cyclin B1 in the Gcn1ΔRWDBD MEFs. Our results demonstrated, for the first time, that GCN1 is essential for both GCN2-dependent stress response and GCN2-independent cell cycle regulation

Curettage and external fixation for displaced pathological fracture through non-ossifying fibroma in the radius: A case report

Non-ossifying fibromas are extremely rare in the upper extremity, such as those in the radius and humerus. The treatment of completely displaced fractures following non-ossifying fibromas in the radius has not been reported. We present the case of a pathological fracture caused by a non-ossifying fibroma in the radius treated using external fixation. The patient was a 10-year-old girl who presented to our hospital with right forearm pain after an accidental fall. She had no remarkable medical history. Radiographs and computed tomography showed a pathological fracture through osteolytic lesions with sclerotic rims in the diaphysis of the radius, suggesting a pathological fracture through a non-ossifying fibroma in the radius. We performed tumor curettage and external fixation due to marked fracture displacement. Histological findings were compatible with those of non-ossifying fibroma. Six months post-surgery, there were no limitations in the range of motion of supination and pronation of the forearm, and radiographs confirmed a bone union. Although non-ossifying fibromas in the radius are rare, cases with large lesions can cause pathological fractures after minor trauma. This case suggests that curettage and external fixation are beneficial, especially if early surgery is required due to unacceptable displacement and when there is no time for a biopsy to rule out malignancy

Plate fixation using parallelogram prism iliac bone grafts for clavicle oblique nonunion with shortening deformity: a case report

Abstract Background Plate fixation using a tricortical iliac bone graft can provide a high ratio of bone union and restore clavicle length in cases of atrophic nonunion. However, the surgical treatment of clavicle oblique nonunions with marked shortening deformity remains challenging and unresolved. Here, we describe a case of clavicle oblique nonunion with shortening that was treated using plate fixation with parallelogram prism iliac bone grafts. Case presentation A 46-year-old man presented to our hospital with severe medial scapular pain. He had been diagnosed with a right clavicle mid-shaft fracture in a motorcycle accident 9 months earlier. He underwent conservative treatment, but radiographs and computed tomography showed clavicle oblique nonunion with marked shortening. Physical examination revealed no pain at the nonunion site; however, tenderness was noted on the medial side of the right scapula and protrusion of the inferior scapular angle was prominent. His symptoms interfered with daily life and required surgery. After release of the nonunion, we harvested the parallelogram prism bone grafts from the iliac crest. We inserted these bone grafts into the fracture ends and fixed them with lag screws, after which we performed plate fixation. Immediately after surgery, right medial scapular pain and scapula winging subsided. Bone union was achieved, and the length of the clavicle was restored at 9 months postoperatively. Conclusions This case report provides new information on the surgical treatment of clavicle oblique nonunion with shortening deformity. The presence of medial scapular pain and winging scapula can be clinically problematic in cases of clavicle nonunion with marked shortening. Our case revealed that reliable bone union and clavicle length recovery can be achieved with plate fixation and iliac bone grafts

Influence of Proximal Humeral Cortical Bone Thickness on the Radiographic Outcome After Osteosynthesis of Proximal Humeral Fractures: Propensity Matching Score Analysis

Introduction Osteoporosis can affect the surgical outcomes of proximal humeral fractures in older people. Recently, the cortical bone thickness of the proximal humerus on plain radiograph has been proposed to reflect local osteoporosis of the proximal humerus; however, its effect on the surgical outcome of proximal humeral fractures remains unclear. The purpose of this study is to investigate the influence of cortical bone thickness on postoperative radiographic outcomes after osteosynthesis for proximal humeral fractures. Materials and Methods We retrospectively identified 190 patients (≥50 years) who underwent osteosynthesis with an intramedullary nail or plate for proximal humeral fractures. The patients were categorized into 2 groups according to the cut-off value of an average proximal humerus cortical bone thickness of 6 mm on plain radiographs: patients with and without local osteoporosis. After propensity score matching, we compared the incidence of postoperative radiographic complications between the 2 groups. We also performed subgroup analyses of outcomes in a subgroup of patients who underwent intramedullary nailing and those who underwent plate fixation. Results Propensity score matching yielded 60 patients in each group. No significant difference in complication rates was observed between the 2 groups. However, in the intramedullary nailing subgroup, the incidence of reduction loss was significantly higher in patients with local osteoporosis than in those without local osteoporosis (51.7% vs 14.3%, P = .002). Discussion The proximal humeral cortical bone thickness had no significant effect on the overall radiographic outcome; however, reduction loss after intramedullary nailing was susceptible to local osteoporosis of the proximal humerus. Conclusion Our study suggests that plate fixation is advantageous in preventing postoperative reduction loss in patients with lower cortical bone thickness

Direct Measurement of Chain Diffusion at Interfaces of PPO/PS Bilayer Films by Nano-Thermal Analysis and Time-of-Flight Secondary Ion Mass Spectrometry

Chain diffusion at the polyphenylene oxide/polystyrene (PPO/PS) interface of bilayer films were investigated using nanothermal analysis (nano-TA) and time-of-flight secondary ion mass spectrometry (TOF–SIMS). An ultralow-angle slicing technique by the surface and interfacial cutting analysis system (SAICAS) was used to expand the size of the interfacial region effectively. The glass-transition temperature (<i>T</i>_g) at the interface was directly evaluated by nano-TA. The gradient of <i>T</i>_g at the PPO/PS interface became broad after annealing. An increase in annealing time caused an increase in the <i>T</i>_g of the initial PS layer, indicating that the PPO diffused across the interface. Since PPO/PS is a compatible blend system, the local chemical compositions were evaluated by Fox equation. The methodology presented here is useful for interfacial analyses of various polymer composite systems and is beneficial because the isotope labeling is not necessary