Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability.

FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2'-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient-derived cells. Loss of 2'-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.

Correlation of insulin-like growth factor 1 and osteoarthritic cartilage degradation: a spontaneous osteoarthritis in guinea-pig.

OBJECTIVE: The pathogenesis of osteoarthritis centers on the imbalance between catabolic and anabolic processes in cartilage metabolism. Insulin growth factor 1 (IGF-1) has been shown to have anabolic effects in cartilage in vitro. This study aim to determine whether IGF-1 on cartilage is associated with loss of chondrocyte and extracellular matrix breakdown using the Hartley guinea pig model. MATERIALS AND METHODS: Cartilage from the medial and lateral tibial plateau of 6-month and 12-month old Hartley guinea pigs were used for this study. Histological analysis was performed with hematoxylin-eosin (HE) and toluidine blue staining. Safranin-O staining was used to quantify proteoglycan (PG) loss and the extent of cartilage damage by Modified Mankin score. Distribution of IGF-1 was demonstrated with in situ hybridization techniques. IGF-1 mRNA levels were assessed using Real-time PCR. RESULTS: Histological loss of chondrocytes, and cartilage matrix and decreased IGF-1 distribution were demonstrated in a temporal and spatial manner. Compared to the 6-month old samples, the 12-month specimens had significantly cartilage degeneration and less cartilage matrix and PGs staining. Decreased level of IGF-1 was also observed in the 12-month samples. These observations were more pronounced in the medial tibial plateau when compared to the lateral plateau. CONCLUSIONS: The decreased level of IGF-1 may play a critical role for maintaining the balance between catabolic and anabolic processes in cartilage metabolism during the development of osteoarthritis. Thus, the increase of IGF-1 may be applicable to developing OA therapy.

[Clinical effects of simple hallux valgus surgery for transfer metatarsalgia].

Objective: To analyze the clinical effects of simple hallux valgus surgery for transfer metatarsalgia. Methods: From September 2011 to November, a total of 21 patients(30 feets)with transfer metatarsalgia of hallux valgus and underwent the simple hallux valgus surgery without lateral metatarsal shortening osteotomy In Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, were enrolled in the study.The hallux valgus angle (HVA), intermetatarsal angle (IMA) , AOFAS scale and analogue score (VAS) were measured pre-operation and a half year, one year, two years after operation.The data were measured repeatedly and analyzed with analysis of variance. Results: The mean preoperative HVA changed [(39.6±9.7), (14.2±7.9), (14.8±7.9), (13.2±6.5)°] at 6 months, 1 year and 2 years follow-up; the mean IMA decreased [(13.8±4.0), (4.5±4.3), (5.8±3.9), (5.4±4.9)°] at 6 months, 1 year and 2 years follow-up(all P<0.001).63.5% of metatarsalgia cases improved, and 73.1% of painful callosities disappeared postoperatively.All the patients do not require further surgeries. The mean AOFAS for hallux , AOFAS for lesser toes and VAS were improved from 58.96 to 95.42, from 84.38 to 92.04 and from 7.5 to 1.3, respectively. All the results are statistically significant(P<0.001). Conclusion: These results suggest that a simple osteotomy of the first metatarsal provides excellent outcomes with a low rate of complications when compared with the combining lateral metatarsal shortening osteotomy.

One-step approach for the synthesis of CoFe2O4@rGO core-shell nanocomposites as efficient adsorbent for removal of organic pollutants.

CoFe2O4-reduced graphene oxide nanocomposites (CFG) have been successfully synthesized via one-step solvothermal method. The prepared CFG are characterized by X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy (FESEM), vibrating sample magnetometer and so on. The FESEM results show that CFG have uniform core-shell structure with an average diameter of about 75 nm and the thickness of the outer graphene shell is about 15-20 nm. The mass ratio of CoFe2O4 to graphene oxide is a key factor affecting the formation of core-shell hybrids. CFG display much higher adsorption capacity for anionic dyes than cationic dyes owing to the favorable electrostatic interaction. The adsorption capacity for methyl orange is observed as high as 263 mg g-1 at 298 K, and the adsorption isotherms follow the Langmuir model. Furthermore, the specific saturation magnetization (Ms) of CFG is 32.8 emu g-1, and the as-synthesized nanocomposites can be easily separated by external magnetic field after adsorption. The results suggest that CFG have great potential for the practical industrial wastewater treatment.

Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway.

Low-magnitude high-frequency vibration (LMHFV) has been proven to promote osteoporotic fracture healing. Mechanical stimulation was reported to enhance SDF-1/CXCR4 signalling in mesenchymal stem cells (MSCs). We hypothesised that LMHFV promoted osteoporotic fracture healing by enhancing MSC migration through the SDF-1/CXCR4 pathway. 152 ovariectomised SD-rats received closed femoral fracture in groups of vibration+MSC (VMG) (20 min/d, 5 d/week), vibration+MSC+AMD3100 (VMAG; AMD, a CXCR4 inhibitor) (1 mg/kg/d, intraperitoneal), MSC (MG) (1 × 106 MSC, intracardiac) or control (CG) for a treatment duration of 2, 4 or 8 weeks. MSC migration was evaluated by ex-vivo green fluorescent protein signal in the callus; and fracture healing was examined by weekly radiographs, endpoint computed-tomography and mechanical test. At week-2 and week-4, ex-vivo callus GFP intensity of VMG was significantly higher than other groups (p < 0.05). From week-2 to week-3, both callus width and callus area in VMG were significantly larger; and from week-7 to week-8, smaller than other groups (p < 0.05). At week-8, high-density bone volume fraction, bone volume fraction, bone mineral density and stiffness in VMG were significantly higher than other 3 groups (p < 0.05). This study demonstrated that LMHFV promoted MSC migration and fracture healing in osteoporotic rats. This effect was attenuated by CXCR4 inhibitor, providing strong evidence that SDF-1-mediated MSC migration was one of the important mechanisms through which LMHFV enhanced fracture healing.

Prevention strategies for occupational low back pain.

Among the strategies to prevent occupational LBP, only job design/redesign and exercise programs appear to have a protective effect; however, the studies pertaining to exercise remain contradictory, and controlled trials evaluating ergonomics interventions are lacking. Risk factor modification is beneficial from a general health perspective, but studies are contradictory with respect to its role in prevention of LBP. There is no conclusive evidence to support the use of structured education programs in the workplace, and the cost of these programs is not justified. There is no support for the use of orthotics or worker selection methods based on the available data, and these methods should not be employed in the workplace. Despite efforts from the medical community and industry, there is little evidence that there has been a substantial impact on the prevalence of LBP and disability. Further work is needed in both occupational and nonoccupational settings to determine effective prevention strategies for LBP in the future.

Adult worm homogenate of the nematode parasite Heligmosomoides polygyrus induces proliferation of naive T lymphocytes without MHC restriction.

The documented in vitro response of mouse T cells to parasite antigens is typically anamnestic and H-2 restricted. As yet, there have been no confirmed reports of the existence of a non-H-2-restricted, superantigen type of response to the antigens of metazoan parasites. Reported here are data which show that antigens produced by the adult stage of the nematode parasite Heligmosomoides polygyrus (= Nematospiroides dubius) can stimulate naive T cells in vitro to proliferate and produce IL-2. A series of T cell hybridomas has been used to show that adult worm homogenate of H. polygyrus can stimulate parasite antigen naive T cells. This response is independent of the H-2 haplotype of the antigen-presenting accessory cells and does not appear to be influenced by the presence or absence of an H-2 E molecule. However, successful presentation of the H. polygyrus superantigen does require the presence of metabolically active accessory cells and fixation of the accessory cells with paraformaldehyde abrogates the response of the target cells. This discovery has important implications for the study of the role of superantigens in host/parasite interactions and will also help to expand current knowledge about the relationship between chronic intestinal nematodes and the host immune system.

Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen.

We have analyzed cytokine gene expression by a murine CD4+ T-cell clone that expresses three forms of T-cell recognition. The clone employs a V beta 6-containing T-cell receptor to recognize (i) a self class II major histocompatibility complex and an ovalbumin-derived peptide (OVA), (ii) an I-Ab alloantigen, and (iii) Mls-1a. All three responses are accompanied by similar levels of cell proliferation. However, although interferon gamma gene expression is strongly induced during both physiological recognition of the OVA peptide and allogeneic major histocompatibility complex recognition, expression of this gene was not detected during the Mls response. These studies indicate that Mls recognition is functionally distinct from T-cell recognition of peptides and alloantigens and leads to an alternative pattern of cytokine gene expression. They also suggest the possibility that encounter with these two classes of T-cell antigen in vivo may generate subsets of T helper cells that display different patterns of cytokine gene expression.

Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during the development of murine autoimmune disease.

The development of autoimmune disease in the MRL/MpJ-lpr inbred mouse strain depends upon the maturation of a subset of T lymphocytes that may cause sustained activation of immunological effector cells such as B cells and macrophages. We tested the hypothesis that abnormal effector cell activation reflects constitutive overexpression of a T cell cytokine. We found that a newly defined T cell cytokine, Eta-1, is expressed at very high levels in T cells from MRL/l mice but not normal mouse strains and in a CD4-8- 45R+ T cell clone. The Eta-1 gene encodes a secreted protein that binds specifically to macrophages, possibly via a cell adhesion receptor, resulting in alterations in the mobility and activation state of this cell type (Patarca, R., G. J. Freeman, R. P. Singh, et al. 1989. J. Exp. Med. 170:145; Singh, R. P., R. Patarca, J. Schwartz, P. Singh, and H. Cantor. 1990. J. Exp. Med. 171:1931). In addition, recent studies have indicated that Eta-1 can enhance secretion of IgM and IgG by mixtures of macrophages and B cells (Patarca, R., M. A. Lampe, M. V. Iregai, and H. Cantor, manuscript in preparation). Dysregulation of Eta-1 expression begins at the onset of autoimmune disease and continues throughout the course of this disorder. Maximal levels of Eta-1 expression and the development of severe autoimmune disease reflect the combined contribution of the lpr gene and MRL background genes.

Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.

We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.