GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.

Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.

Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Role of Galectin-3 in intervertebral disc degeneration: an experimental study.

BACKGROUND: This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. METHODS: The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. RESULTS: With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P < 0.05). GB1107 (25 µmol/L) also significantly promoted the apoptosis of cartilage endplate cells (P < 0.05). Moreover, the percentage of cartilage endplate cells in the G1 phase was significantly higher, while that in the G2 and S phases was significantly lower (P < 0.05). Additionally, the mRNA and protein expression levels of MMP3, CCL3, and Aggrecan in rat cartilage end plate cells were lower than those in the control group. CONCLUSIONS: Galectin-3 decreases with the progression of the cartilage endplate degeneration of the intervertebral disc. Galectin-3 may affect intervertebral disc degeneration by regulating the degradation of the extracellular matrix.

Oxidation of Toluene over Mesoporous MnO2/CeO2 Nanosphere Catalysts: Effects of the MnO2 Precursor and the Type of Support.

Toluene is the most common volatile organic compound (VOC), and the MnO2-based catalyst is one of the excellent nonprecious metal catalysts for toluene oxidation. In this study, the effects of MnO2 precursors and the support types on the oxidation performance of toluene were systematically explored. The results showed that the 15MnO2/MS-CeO2-N catalyst with Mn(NO3)2·4H2O as the precursor and the mesoporous CeO2 nanosphere (MS-CeO2) as the support exhibited the most excellent performance. To reveal the reason behind this phenomenon, the calcination process of the catalyst precursor and the reaction process of toluene oxidation were investigated by in situ DRIFTS. It was found that the MnO2 precursor and the type of catalyst support could have a large effect on the reaction pathway and the produced intermediates. Therefore, the roles of the MnO2 precursor and the type of support should be key considerations when developing the high-performance MnO2-based toluene oxidation catalyst.

Broadband ultraviolet plasmonic enhanced AlGaN/GaN heterojunction photodetectors with close-packed Al nanoparticle arrays.

Plasmonic metallic nanostructures could concentrate optical fields into nanoscale volumes and support efficient light scattering and absorption, which therefore stimulates the continuing development of advanced plasmonic-assisted semiconductor photodetectors. In this work, by fabricating Al nanoparticle (NP) arrays in AlGaN surface using the AAO template transferring method, significant broadband ultraviolet (UV) photoresponse enhancement was demonstrated on AlGaN/GaN heterojunction photodetectors. By deliberately designing the close-packed Al NP arrays, the broadband UV plasmonic resonance with large optical field absorption and strong interface field enhancement are enabled, hence, the highest responsivity exceeding 8.1 A W-1 and maximum external quantum efficiency of 3500% was obtained at the resonance wavelength 292 nm, revealing more than 80 times the excellent enhancement in responsivity. Specifically, owing to coupling among NPs at the Al/AlGaN interface, the smaller size Al NP array exhibits an excellent photoresponse enhancement encompassing the entire UV band compared to the relatively larger size Al NP array. In addition, different photoresponse enhancements depending on the applied bias were observed. The Al NPs detector also demonstrates a fast photoresponse with a rise time of around 60 ms and a relatively long fall time of 1.42 s. This work could be of great significance for gaining a low and efficient approach to achieve plasmonic-empowered heterojunction broadband UV detectors.

Paediatric lung injury due to accidental ingestion of meperfluthrin: a case report.

BACKGROUND: It is common for children to accidentally ingest chemical drugs with different degrees of toxicity. Meperfluthrin is a highly effective and easy-to-use pyrethroid pesticide with low toxicity. It is widely used in electric mosquito coils. This type of electric mosquito coil is used in daily life, which increases the chance of exposure among children and, consequently, may lead to accidental ingestion. There are only few reports of meperfluthrin poisoning causing lung injury in children. We report a rare clinical case of lung injury wherein a child ingested meperfluthrin orally. CASE PRESENTATION: We report the case of a 1-year-old boy who accidentally swallowed an electric mosquito coil containing meperfluthrin and developed cough and fever. The patient's parents observed him swallowing the electric mosquito coil (Qiangshou®). Although he was stopped, the child had already swallowed approximately 10 ml of the liquid. According to the instructions, it contained 9 mg/ml of meperfluthrin, thus, it was assumed that he ingested meperfluthrin at a dose of approximately 90 mg. Computed tomography (CT) of his lungs showed uneven brightness in both lungs with multiple spots, scaly shadows, and mesh. Density of the shadows indicated lung parenchymal and interstitial lung disease. Lung tidal function tests indicated obstructive ventilation dysfunction. After evaluation and treatment, his cough drastically reduced, his fever disappeared, and his lung CT findings showed improvement. Therefore, accidental ingestion of meperfluthrin led to acute lung injury in a paediatric patient. Because of prompt treatment, his lung lesions recovered well. CONCLUSIONS: Meperfluthrin causes airway mucosal damage and hypersensitivity. Lung CT and lung tidal function measurements can be used to monitor changes in the condition. Presently, there is a lack of specific detoxification drugs for meperfluthrin poisoning. Thus, the focus of treatment is to protect the airway mucosa and reduce inflammatory reactions.

One-Step Route to Fe2O3 and FeSe2 Nanoparticles Loaded on Carbon-Sheet for Lithium Storage.

Iron-based anode materials, such as Fe2O3 and FeSe2 have attracted widespread attention for lithium-ion batteries due to their high capacities. However, the capacity decays seriously because of poor conductivity and severe volume expansion. Designing nanostructures combined with carbon are effective means to improve cycling stability. In this work, ultra-small Fe2O3 nanoparticles loaded on a carbon framework were synthesized through a one-step thermal decomposition of the commercial C15H21FeO6 [Iron (III) acetylacetonate], which could be served as the source of Fe, O, and C. As an anode material, the Fe2O3@C anode delivers a specific capacity of 747.8 mAh g-1 after 200 cycles at 200 mA g-1 and 577.8 mAh g-1 after 365 cycles at 500 mA g-1. When selenium powder was introduced into the reaction system, the FeSe2 nano-rods encapsulated in the carbon shell were obtained, which also displayed a relatively good performance in lithium storage capacity (852 mAh g-1 after 150 cycles under the current density of 100 mA·g-1). This study may provide an alternative way to prepare other carbon-composited metal compounds, such as FeNx@C, FePx@C, and FeSx@C, and found their applications in the field of electrochemistry.

Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis.

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.

Intelligent Micro/nanomotors with Taxis.

Micro/nanomotors (MNMs) are micro/nanoscale devices that can convert energy from their surroundings into autonomous motion. With this unique ability, they may revolutionize application fields ranging from active drug delivery to biological surgeries, environmental remediation, and micro/nanoengineering. To complete these applications, MNMs are required to have a vital capability to reach their destinations. Employing external fields to guide MNMs to the targets is common and effective way. However, in application scenarios where targets are generally unknown or dynamically change, MNMs must possess the capability of self-navigation or self-targeting. Taking advantage of tactic movements toward or away from signal sources, numerous intelligent MNMs with self-navigation or self-targeting have been demonstrated and attracted much attention during the past few years. In this Account, we elucidate the intelligent response mechanisms of such tactic MNMs, which are summarized as two main models. One is that local vector fields, including those of chemical concentration gradients, gravity, flows, and magnetic fields existing in systems, achieve the overall alignment of asymmetric MNMs via aligning torques, directing the MNMs to swim toward or away from the signal sources. Another is that isotropic MNMs may produce propulsion forces with direction solely determined by the local vector field regardless of their Brownian rotations. Then we discuss and highlight the recent progress in tactic MNMs, including chemotactic, phototactic, rheotactic, gravitactic, and magnetotactic motors. Artificial chemotactic MNMs can be designed with different morphologies and compositions if asymmetric reactions are associated with chemical concentration gradients. In these systems, asymmetric phoretic slip flows are induced, leading to torques that enable the anisotropic particles to align and exhibit chemotaxis. For phototactic MNMs, light irradiation establishes asymmetric fields surrounding the motors via light-induced chemical reactions or physical effects to generate phototactic motion. Shape-asymmetric MNMs reorient in natural fluid flows because of torques applied by the flows, inducing rheotactic movements. MNMs with either the centroid or magnetic components distributed asymmetrically maintain orientation under the torque triggered by gravity or magnetic forces, generating tactic motions. In the end, we envision the future development of synthetic tactic MNMs, including enhancement of the sensitivity of motors to target signals, increasing the diversity of chemical motor systems, and combining multiple mechanisms to endow the tactic motors with multiple functionality. By highlighting the current achievements and offering our perspective on tactic MNMs, we look forward to inspiring the emergence of the next generation of intelligent MNMs with taxis.

A Genetic Predictive Model Estimating the Risk of Developing Adolescent Idiopathic Scoliosis.

BACKGROUND: Previous GWASs have revealed several susceptible variants associated with adolescent idiopathic scoliosis (AIS). Risk prediction based on these variants can potentially improve disease prognosis. We aimed to evaluate the combined effects of genetic factors on the development of AIS and to further develop a genetic predictive model. METHODS: A total of 914 AIS patients and 1441 normal controls were included in the discovery stage, which was followed by the replication stage composed of 871 patients and 1239 controls. Genotyping assay was performed to analyze 10 previously reported susceptible variants, including rs678741 of LBX1, rs241215 of AJAP1, rs13398147 of PAX3, rs16934784 of BNC2, rs2050157 of GPR126, rs2180439 of PAX1, rs4940576 of BCL2, rs7593846 of MEIS1, rs7633294 of MAGI1 and rs9810566 of TNIK. Logistic regression analysis was performed to generate a risk predictive model. The predicted risk score was calculated for each participant in the replication stage. RESULTS: The association of the 10 variants with AIS was successfully validated. The established model could explain approximately 7.9% of the overall variance. In the replication stage, patients were found to have a remarkably higher risk score as compared to the controls (44.2 ± 14.4 vs. 33.9 ± 12.5, p <0.001). There was a remarkably higher proportion of the risk score i.e. >40 in the patients than in the controls (59% vs. 28.9%, p <0.001). CONCLUSION: Risk predictive model based on the previously reported genetic variants has a remarkable discriminative power. More clinical and genetic factors need to be studied, to further improve the proba-bility to predict the onset of AIS.

Carbon Dioxide Captured by Metal Organic Frameworks and Its Subsequent Resource Utilization Strategy: A Review and Prospect.

The carbon dioxide (CO2) is notorious as the greenhouse gas, which could cause the global warming and climate change. Therefore, the reduction of the atmospheric CO2 emissions from power plants and other industrial facilities has become as an increasingly urgent concern. In the recent years, CO2 capture and storage technologies have received a worldwide attention. Adsorption is considered as one of the efficient options for CO2 capture because of its cost advantage, low energy requirement and extensive applicability over a relatively wide range of temperature and pressure. The metal organic frameworks (MOFs) show widely potential application prospects in CO2 capture and storage owing to their outstanding textural properties, such as the extraordinarily high specific surface area, tunable pore size, ultrahigh porosity (up to 90%), high crystallinity, adjustable internal surface properties, and controllable structure. Herein, the most important research progress of MOFs materials on the CO2 capture and storage in recent years has been comprehensively reviewed. The extraordinary characteristics and CO2 capture performance of Zeolitic Imidazolate Frameworks (ZIFs), Bio-metal organic frameworks (bio-MOFs), IL@MOFs and MOF-composite materials were highlighted. The promising strategies for improving the CO2 adsorption properties of MOFs materials, especially the low-pressure adsorption performance under actual flue gas conditions, are also carefully summarized. Besides, CO2 is considered as an abundant, nontoxic, nonflammable, and renewable C1 resource for the synthesis of useful chemicals and fuels. The potential routes for resource utilization of the captured CO2 are briefly proposed.

Selective thoracic fusion for adolescent thoracic scoliosis secondary to Chiari I malformation: a comparison between the left and the right curves.

PURPOSE: The aim of this study was to compare the clinical outcomes of selective thoracic fusion in the surgical treatment of Chiari malformation type I (CMI) adolescents with different curve patterns. METHODS: Sixty-three CMI patients with left thoracic curve (LTC) and 63 age- and curve-magnitude-matched CMI patients with right thoracic curve (RTC) were recruited. Selective thoracic fusion was performed for two groups. The coronal and sagittal parameters including the thoracic and lumbar Cobb angle, apical vertebral translation, trunk shift, thoracic kyphosis (TK), lumbar lordosis and sagittal vertical axis were measured before surgery, immediately postoperative and at the final follow-up. The accuracy of pedicle screw placement between both groups was also compared. RESULTS: All preoperative radiographic parameters were matched in both groups except for TK (LTC group 40.1° vs. RTC group 23.0°, P = 0.021). The immediately postoperative spontaneous correction of the lumbar curve was 56.9% in LTC group, which was remarkably lower than in RTC patients (67.9%). Patients with LTC were found to have obviously increased trunk shift than those with RTC (15.1 mm vs. 8.0 mm, P = 0.038). At the final follow-up, the correction of the thoracic curve was comparable between the two groups (59.9% vs. 62.6%, P = 0.610). The rate of the pedicle screw perforations was similar between both groups. CONCLUSIONS: Patients with LTC and RTC can both be successfully corrected through selective thoracic fusion with a promising long-term surgical outcome. CMI patients with RTC tend to have a better spontaneous correction of the lumbar curve after surgery. These slides can be retrieved under Electronic Supplementary Material.

Rare variant of HSPG2 is not involved in the development of adolescent idiopathic scoliosis: evidence from a large-scale replication study.

BACKGROUND: Rare variants of HSPG2 have recently been reported to function as a potential contributor to the susceptibility of adolescent idiopathic scoliosis (AIS) in the Caucasians. A replication study in the different population is warranted to validate the role of HSPG2 in AIS. The aim of this study was to determine the association between HSPG2 and AIS in the Chinese patients and to further investigate its influence on the phenotype of the patients. METHODS: SNVs p.Asn786Ser of HSPG2 was genotyped in 1752 patients and 1584 normal controls using multiple ligase detection reactions. The mRNA expression of HSPG2 in the paraspinal muscles was quantified for 90 patients and 26 controls. The The Student's t test was used to analyze the inter-group comparison of the HSPG2 expression. The relationship between the HSPG2 expression and the curve magnitude of the patients was analyzed by the Pearson correlation analysis. RESULTS: No case of mutation in the reported SNV p.Asn786Ser of HSPG2 was found in our cohort. The mRNA expression of HSPG2 in patients was comparable with that in the controls (0.0016 ± 0.0013 vs. 0.0019 ± 0.0012, p = 0.29). 42 patients with curve magnitude > 60 degrees were assigned to the severe curve group. The other 58 patients were assigned to the moderate curve group. These two groups were found to have comparable HSPG2 expression (0.0015 ± 0.0011 vs. 0.0017 ± 0.0014, p = 0.57). And there was no remarkable correlation between the expression level of HSPG2 and the curve severity (r = 0.131, p = 0.71). CONCLUSIONS: HSPG2 gene was not associated with the susceptibility or the phenotypes of AIS in the Chinese population. The whole HSPG2 gene can be sequenced in more AIS patients to identify potentially causative mutations.

CEP55 promotes the proliferation and invasion of tumour cells via the AKT signalling pathway in osteosarcoma.

The molecular mechanisms underlying the development of osteosarcoma (OS) are not fully understood. In this study, we investigated for the first time the clinical significance and biological activity of centrosomal protein 55 (CEP55) in OS. We found that CEP55 was overexpressed in OS, and the CEP55 expression level in OS was correlated with metastasis and poor prognosis. Through in vitro experiments, we confirmed that CEP55 knockdown significantly induced cell cycle arrest at G1 phase and suppressed OS cell proliferation, migration and invasion. In addition, CEP55 knockdown suppressed OS tumour growth in nude mice. Global gene expression profiling of CEP55-silenced MNNG/HOS cells showed that the AKT pathway might be involved in the regulation of OS cell activity. Two downstream factors of AKT signalling, CCND1 and FN1, were found to have significantly higher expression in tumour tissues, and their mRNA expression levels were strongly correlated with CEP55 expression. To conclude, our data suggest that CEP55 can be used as a prognostic marker for OS, highlighting the significance of CEP55 signalling as a putative therapeutic target.

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.

Vertebral subluxation during three-column osteotomy in surgical correction of adult spine deformity: incidence, risk factors, and complications.

PURPOSE: To investigate incidence, risk factors, and complications of vertebral subluxation (VS) during three-column osteotomy in surgical correction of adult spine deformity. METHODS: Adult spine deformity patients who underwent three-column osteotomies including VCR, PSO, and other modified types from March 2000 to December 2014 in our center were retrospectively reviewed. The following parameters were measured pre- and postoperatively: Cobb angle of main curve, global kyphosis, sagittal vertical axis, and kyphosis flexibility. Radiographic parameters between groups (VCR vs. PSO and subluxation vs. non-subluxation) were compared. RESULTS: 171 ASD patients were recruited, 18 of which (10.5%) developed sagittal vertebral subluxation at the osteotomy site. 5 of 18 patients (27.8%) developed neurological complications after surgery. For these five patients, two patients got partial recovery, and three got complete recovery at 2-year follow-up. 116 patients underwent PSO, 12 of which (10.3%) developed sagittal vertebral subluxation. In 55 patients receiving VCR, 6 (10.9%) developed sagittal vertebral subluxation. No significant difference was noted between the two groups (P > 0.05). The mean age of VS group was larger than that of non-VS group (46.2 vs. 34.2, P < 0.05). VS group had less kyphosis flexibility (11 vs. 23%, P < 0.05). More patients in VS group had preoperative sagittal VS as compared to non-VS group (77.8 vs. 20.9%, P < 0.05). VS group had more neurological complications than non-VS group (25 vs. 5.4%, P < 0.05). CONCLUSION: VS occurred in one-tenth of patients receiving three-column osteotomies, one-fourth of which would develop neurological deficits. Older age, rigid kyphosis, and the pre-existence of VS were risk factors for developing VS.

Skull-femoral traction after posterior release for correction of adult severe scoliosis: efficacy and complications.

BACKGROUND: It is a great challenge for spine surgeons to correct severe rigid scoliosis. We developed a three- staged correction (one stage posterior release and screw placement, two stage skull-femoral traction and three stage posterior instrumentation) for adult severe scoliosis. The objective of this study is to investigate safety and efficacy of a three- staged correction for adult severe scoliosis. METHODS: A retrospective review was performed for patients with severe scoliosis receiving three- staged correction (one stage posterior release and screw placement, two stage skull-femoral traction and three stage posterior instrumentation) from June 2001 to October 2014. The inclusion criteria were as follows: [1] age more than 18 years; [2] main curve larger than 90°; [3] a minimum 2-year follow-up. Patients were excluded if they had a history of surgery or anterior release or receiving three column osteotomies. RESULTS: A total of 63 patients were included (37 female and 26 male), with a mean age of 22.7 years (range: 18-30 years) and follow-up of 42.6 months (range: 24-108 months). The aetiology was congenital in 27 patients, neuromuscular in 18, idiopathic in 11, neurofibromatosis-1 in 4 and Marfan syndrome in 3. The mean traction weight was 28.4 kg (range: 18-32 kg), equal to 57.2% of patients' body weight (range: 42.7-72.3%). The mean traction time was 22.7 days (range: 12-44 days). Postoperative correction rate was 55% (range: 38-78%) for scoliosis and 51% (range: 32-75%) for kyphosis. Contribution of traction to correction was 51% (range: 36-70%) for scoliosis and was 43% (range: 34-55%) for kyphosis. CONCLUSIONS: Three- staged correction (one stage posterior release and screw placement, two stage skull-femoral traction and three stage posterior instrumentation) could effectively correct adult severe scoliosis. The incidence of complications of skull-femoral traction was not low, but transient and could be successfully managed.

Abnormal PITX1 gene methylation in adolescent idiopathic scoliosis: a pilot study.

BACKGROUND: The gene of pituitary homeobox 1 (PITX1) has been reported to be down-regulated in adolescent idiopathic scoliosis (AIS), of which the cause has not been well addressed. The abnormal DNA methylation was recently assumed to be an important mechanism for the down-regulated genes expression. However, the association between PITX1 promoter methylation and the etiology of AIS was not clear. METHODS: The peripheral blood samples of 50 AIS patients and 50 healthy controls were collected and the genomic DNA was extracted. The pyrosequencing assay was used to assess the methylation status of PITX1 promoter and real-time quantitative polymerase chain reaction (PCR) was used to detect the PITX1 gene expression. Comparison analysis was performed using independent t test and Chi-square tests, while correlation analysis were performed with 2-tailed Pearson coefficients. RESULTS: The mean methylation level was (3.52 ± 0.96)% in AIS and (1.40 ± 0.81)% in healthy controls (P < 0.0001). The PITX1 gene expression was 0.15 ± 0.08 in AIS and 0.80 ± 0.55 in healthy controls (P < 0.0001). The comparative analysis showed significant difference in age (P = 0.021) and Cobb angle of the main curve (P = 0.0001) between AIS groups with positive and negative methylation. The methylation level of 6 CpG sites in PITX1 promoters was significantly associated with Cobb angle of the main curve (P < 0.001) in AIS. No statistical relationship between PITX1 promoter methylation and gene expression was found in AIS (P = 0.842). CONCLUSION: Significantly higher methylation level and lower PITX1 gene expression are found in AIS patients. PITX1 methylation is associated with Cobb angles of the main curves in AIS. DNA methylation thus plays an important role in the etiology and curve progression in AIS.

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.