The nanoscale organization of Nipah virus matrix protein revealed by super-resolution microscopy.

The matrix proteins (M) of many enveloped RNA viruses mediate virus assembly and budding. However, it remains poorly understood how M are involved in virus budding and how they interact with envelope proteins. Here, we show that the expression level of Nipah (NiV) M in particles produced by the host cells deviates from a gamma distribution and does not reflect that of the host cells, indicating assembly of the NiV-M in the process. Our data reveal that NiV-M affects the circularity of the particles while the NiV envelope proteins do not. The organization of NiV envelope proteins on the membrane of the particles is similar to those that do not express NiV-M, suggesting that NiV-M does not directly interact with the envelope proteins during assembly and budding.

[Effect of long non-coding RNA MBNL1-AS1 expression on prognosis of acute myeloid leukemia patients].

Objective: To explore the prognosis effect of the expression of long-chain non-coding RNA (lncRNA) MBNL1-AS1 on acute myeloid leukemia (AML) patients. Methods: One hundred and twenty-five AML patients of the Cancer Genome Atlas (TCGA) from November 2001 to March 2010 were involved, including 70 patients who received chemotherapy only and other 55 patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in addition to chemotherapy. According to the median expression of lncRNA MBNL1-AS1, patients of chemotherapy group were divided into high expression sub-group(n=35) and low expression sub-group (n=35), and patients of allo-HSCT group were also divided into high expression sub-group (n=28) and low expression sub-group (n=27) for prognosis analysis. Clinical characteristics at diagnosis, including peripheral white blood cell counts (WBC), blast percentages in peripheral blood and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations in AML were described. The event-free survival (EFS) rate and overall survival (OS) rate of patients in different groups were analyzed, and the influence of the clinical characteristics of patients on the prognosis of AML was analyzed by COX multivariate analysis. Results: In the chemotherapy group, patients with low lncRNA-MBNL1-AS1 expression had significantly lower EFS and OS (60.0%, 8.6%) than patients with high lncRNA-MBNL1-AS1 expression (68.6%, 34.3%) (χ²=7.817, 10.880, all P<0.01). However, in the alloHSCT group, no significant differences were observed in EFS and OS of patients between high and low expression groups of lncRNA-MBNL1-AS1 (all P>0.05). COX multivariate analysis confirmed that age≥60 years old (EFS: HR (95%CI): 6.934 (1.918-25.075),P=0.003;OS: HR (95%CI): 4.119 (1.812-9.364), P=0.001), and low expression of lncRNA MBNL1-AS1 (EFS: HR (95%CI): 0.354 (0.126-0.941), P=0.038; OS: HR (95%CI): 0.424 (0.231-0.778), P=0.006)were independent risk factors for EFS and OS in the chemotherapy group. Conclusion: The long-chain non-coding RNA MBNL1-AS1 is related to the prognosis of AML, and its low expression is an independent poor prognostic factor in AML patients.

Simultaneous multi-slice accelerated diffusion-weighted imaging with higher spatial resolution for patients with liver metastases from neuroendocrine tumours.

AIM: To evaluate the imaging characteristics of simultaneous multi-slice (SMS) accelerated diffusion-weighted imaging (DWI) with decreased section thickness, with and without motion correction, in comparison to conventional DWI (cDWI) for the detection of lesions in patients with neuroendocrine tumour (NET) liver metastases. MATERIALS AND METHODS: Fifteen patients with NET liver metastases underwent cDWI (section thickness [SL]=4 mm) and SMS-DWI (SL=2 mm). Non-linear motion-corrected (Moco)-SMS-DWI was generated in addition to the original series. Qualitative imaging characteristics (five-point Likert scale), the number of high signal lesions, and the detectability and delineation of lesions were evaluated and compared using the Friedman and the Dunn-Bonferroni tests. The test-retest variability (TRV) of the cDWI and SMS-DWI techniques was investigated among 11 healthy volunteers who underwent cDWI (SL=4 mm) and SMS-DWI (SL=4 mm) twice. The Friedman and the Dunn-Bonferroni post-hoc tests were used to compare the mean apparent diffusion coefficient (ADC) and the TRV in different liver regions between the three series. RESULTS: Moco-SMS-DWI demonstrated significantly superior overall image quality (p<0.001) with significantly fewer artefacts (p=0.003) than cDWI. The number of lesions detected by cDWI, SMS-DWI, and Moco-SMS-DWI were 348, 504, and 523, respectively. The detectability and delineation of the lesions and the ADC values were significantly higher on the SMS-DWI and Moco-SMS-DWI images than on the cDWI images (all p<0.001). Moco-SMS-DWI showed significantly higher TRV than cDWI in regions near the liver edge (p=0.018). CONCLUSIONS: SMS-DWI achieves higher spatial resolution than cDWI within the same acquisition time, detects more lesions, and provides better lesion delineation. By applying motion correction, the TRV of DWI could be enhanced in regions near the liver edge.

[Analysis of misdiagnosis causes of suprasellar arachnoid cysts].

Objective: To investigate the causes of misdiagnosis of suprasellar arachnoid cysts, analyze its characteristics and put forward the diagnostic basis and differential points. Methods: The clinical data fo 97 cases of suprasellar arachnoid cysts diagnosed and treated in the neurosurgery department of Beijing Tiantan Hospital and Hebei General Hospital from March 2015 to March 2019 were analyzed retrospectively. All patients underwent CT and MRI scans with obstructive hydrocephalus. 13 cases were misdiagnosed, including 7 males and 6 females. First visit age 1-31 years old, with an average age of 6.3 years. There were 10 patients younger than 6 years old. The remaining 15-year-old patients, 31-year-old patients and 26-year-old patients each have one case. 11 cases were misdiagnosed as obstructive hydrocephalus, 2 cases as cystic craniopharyngioma. Results: 13 cases were misdiagnosed and mistreated, 11 cases were treated with intraventricular and abdominal shunt, 9 cases were treated with neuroendoscopy and recovered well. One cases of intracranial hematomas underwent craniotomy again, the hematomas were removed again and the bone slise were decompressed. One case had fissured stable after shunt. There were no operative deaths and no complications in this group. After endoscopic reoperation, CT and/or MRI scans showed that the ventricle narrowed in varying degrees, some of them returned to normal size and the flow of cerebrospinal fluid (cerebrospinal fluid) was unobstruct at the end of magnetic resonance cerebrospinal fluid angiography (MRI) fistula after endoscopic reoperation. Conclusions: The incidence of suprasellar arachnoid cysts is low, it is rare in clinic and it is easy to misdiagnose and mistreate. At present, it is recognized that the best treatment methods are partial resection of endoscope cyst wall, cyst ventricle fistula and third ventricle floor fisthla.

Visualising the boundary sharpness of uterine zonal structures using high-resolution T2-weighted images during the menstrual cycle.

AIM: To investigate whether there is an optimal time in the menstrual cycle to obtain the best image quality of uterine zonal structures with high-field magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-eight normal volunteers with regular menstrual cycles underwent pelvic 3 T high-resolution T2-weighted three-dimensional (3D) turbo spin echo (TSE) with variable flip angle MRI examinations during the menstrual phase (MP), follicular phase (FP), peri-ovulatory phase (OP), and luteal phase (LP). Two radiologists blinded evaluated the boundary sharpness of the three zonal structures of the uterine corpus and cervix on mid-sagittal images using a three-point Likert-scale. The signal intensity (SI) on T2-weighted sequences of each zonal structure was measured and the ratio between the SI of adjacent structures was calculated. Paired Wilcoxon's test and repeated measurement analysis of variance were used to investigate the differences among the four phases. RESULTS: No variation during the menstrual cycle was found in 10.5% (4/38) of volunteers and their boundaries were all well-defined. The OP exhibited the clearest boundaries of the corpus zonal structures. For the endometrium to junctional zone, mean scores of boundary sharpness from high to low were 3 (OP), 2.97 (FP), 2.76 (LP), 2.74 (MP); that for the junctional zone to myometrium were 2.76 (OP), 2.42 (FP), 2.32 (LP), 2.11 (MP); which were consistent with the SI ratio results. The results for the cervix showed no statistical difference during the menstrual cycle (p>0.05), and was well-defined throughout. CONCLUSIONS: The OP is recommended as the best phase to investigate zonal-related uterine corpus diseases due to the best contrast. For cervical diseases, imaging could be performed when necessary at any time point, due to the limited influence of menstrual phases on cervical zone delineation.

Long non-coding RNA ASAP1-IT1 promotes cell proliferation, invasion and metastasis through the PTEN/AKT signaling axis in non-small cell lung cancer.

OBJECTIVE: To investigate the relative expression of long non-coding RNA (lncRNA) ASAP1-IT1 (hereafter called ASAP1-IT1) in tissues and cells of non-small cell lung cancer (NSCLC) patients, so as to explore the effect of ASAP1-IT1 on the biological effect of NSCLC cells. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to detect the relative expressions of ASAP1-IT1 on tissues of 68 NSCLC patients and 5 cell lines. Besides, the interference sequence of ASAP1-IT1 was designed to detect the transfection efficiency through qRT-PCR experiment. Cell count kit 8 (CCK-8) and clone formation experiment were also carried out to determine the effect of ASAP1-IT1 expression under interference on the proliferation ability of NSCLC cells. In addition, transwell experiment was also performed to investigate the effects of ASAP1-IT1 expression under interference on the invasion and metastasis of NSCLC cells. Furthermore, the Western blotting assay was also conducted to detect the downstream signal pathways through which ASAP1-IT1 regulated the biological behaviors of NSCLC. RESULTS: The results of qRT-PCR experiment showed that in 68 NSCLC samples, upregulation of ASAP1-IT1 expression was identified in 51 samples (82.4%) in comparison with the expression in tumor-adjacent tissues, and a similar upregulation was also observed in 5 NSCLC cells. CCK-8 and clone formation experiments also revealed that interference on ASAP1-IT1 expression could inhibit the proliferation of NSCLC cells, while the transwell experiment showed that the interference on ASAP1-IT1 expression could block the migration and invasion ability of NSCLC cells. The results of Western blotting assay also indicated that ASAP1-IT1 could regulate the biological behaviors of NSCLC cells through phosphatase and tensin homolog deleted on chromosome ten (PTEN)/serine-threonine kinase (AKT) pathway. CONCLUSIONS: In this study, it was found that the expression of ASAP1-IT1 is relatively upregulated in NSCLC cells and tissues, which can promote the proliferation, invasion and metastasis of NSCLC cells through regulating the PTEN/AKT signal pathway. Thus, the therapeutic target of ASAP1-IT1 is expected to provide important ideas for reversing the malignant phenotype of NSCLC in clinical practice.

Anatomic Location of Tumor Predicts the Accuracy of Motor Function Localization in Diffuse Lower-Grade Gliomas Involving the Hand Knob Area.

BACKGROUND AND PURPOSE: The accuracy of preoperative blood oxygen level-dependent fMRI remains controversial. This study assessed the association between the anatomic location of a tumor and the accuracy of fMRI-based motor function mapping in diffuse lower-grade gliomas. MATERIALS AND METHODS: Thirty-five patients with lower-grade gliomas involving motor areas underwent preoperative blood oxygen level-dependent fMRI scans with grasping tasks and received intraoperative direct cortical stimulation. Patients were classified into an overlapping group and a nonoverlapping group, depending on the extent to which blood oxygen level-dependent fMRI and direct cortical stimulation results concurred. Tumor location was quantitatively measured, including the shortest distance from the tumor to the hand knob and the deviation distance of the midpoint of the hand knob in the lesion hemisphere relative to the midline compared with the normal contralateral hemisphere. RESULTS: A 4-mm shortest distance from the tumor to the hand knob value was identified as optimal for differentiating the overlapping and nonoverlapping group with the receiver operating characteristic curve (sensitivity, 84.6%; specificity, 77.8%). The shortest distances from the tumor to the hand knob of ≤4 mm were associated with inaccurate fMRI-based localizations of the hand motor cortex. The shortest distances from the tumor to the hand knob were larger (P = .002), and the deviation distances for the midpoint of the hand knob in the lesion hemisphere were smaller (P = .003) in the overlapping group than in the nonoverlapping group. CONCLUSIONS: This study suggests that the shortest distance from the tumor to the hand knob and the deviation distance for the midpoint of the hand knob on the lesion hemisphere are predictive of the accuracy of blood oxygen level-dependent fMRI results. Smaller shortest distances from the tumor to the hand knob and larger deviation distances for the midpoint of hand knob on the lesion hemisphere are associated with less accuracy of motor cortex localization with blood oxygen level-dependent fMRI. Preoperative fMRI data for surgical planning should be used cautiously when the shortest distance from the tumor to the hand knob is ≤4 mm, especially for lower-grade gliomas anterior to the central sulcus.

Comparison between anti-VEGF therapy and corticosteroid or laser therapy for macular oedema secondary to retinal vein occlusion: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Therapeutic effects of anti-VEGF agents, corticosteroids and laser therapy have been previously examined for treating macular oedema secondary to branch and central retinal vein occlusion (BRVO and CRVO). However, anti-VEGF efficacy has not been previously compared to corticosteroid or laser therapy efficacy. We performed a meta-analysis to compare these treatments. METHODS: Pertinent publications were identified through comprehensive literature searches. Therapeutic effects were estimated using best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP). The Review Manager (version 5.3.5) was used to perform searches. RESULTS AND DISCUSSION: Eleven randomized, controlled trials that included 1045 RVO patients were identified. For eyes with BRVO, anti-VEGF therapy improved BCVA significantly more than corticosteroid/laser therapy at 3 (P=.0002), 6 (P<.00001) and 12 months (P<.00001). For eyes with CRVO, this difference was only significant at 6 months (P=.002). The same was true when efficacy was examined using CRT at 3 and 6 months (BRVO: both P<.00001, CRVO 6 months: P=.02). Long-term efficacy of anti-VEGF agents was limited in eyes with BRVO and CRVO. Improvements in BCVA were similar at 1 and 3 months (P=.74), but BCVA decreased between 3 and 6 months (P=.03). In contrast, BCVA progressively decreased 1 and 6 months following corticosteroid/laser therapy (both P<.00001). Lastly, eyes that had been treated with anti-VEGF agents had significantly lower IOP changes than eyes treated with corticosteroids/laser 3 and 6 months after initiating therapy (both P<.00001). WHAT IS NEW AND CONCLUSION: Anti-VEGF agents improve BCVA and reduce CRT more effectively and longer than corticosteroid/laser in eyes with RVO. Anti-VEGF agents also have a lower risk of elevating IOP. Additionally, anti-VEGF agents are more effective for treating BRVO than CRVO.

[Research progress of treatment strategies for retinitis pigmentosa].

Retinitis pigmentosa (RP) is a genetically heterogeneous group of hereditary retinal disorders characterized by photoreceptor cell death, associated with night blindness, vision loss, progressive peripheral visual field loss and abnormalities in the electroretinogram. A number of gene defects have so far been associated with RP, which cause a progressive loss of rod photoreceptor function, followed by cone photoreceptor dysfunction and eventually complete blindness. The rate of blindness related to RP is high. At present there is no effective therapeutic strategy for RP. In recent years, with the progress of molecular biology technique, many new therapeutic approaches have become promising. This article summarizes the pathogenesis of RP and gives a brief overview of related research progress of RP therapeutic strategies. (Chin J Ophthalmol, 2017, 53: 148-153).

Improving the Grading Accuracy of Astrocytic Neoplasms Noninvasively by Combining Timing Information with Cerebral Blood Flow: A Multi-TI Arterial Spin-Labeling MR Imaging Study.

BACKGROUND AND PURPOSE: Systematic and accurate glioma grading has clinical significance. We present the utility of multi-TI arterial spin-labeling imaging and provide the bolus arrival time maps for grading astrocytomas. MATERIALS AND METHODS: Forty-three patients with astrocytomas (21 men; mean age, 51 years) were recruited. The classification abilities of conventional MR imaging features, normalized CBF value derived from multi-TI arterial spin-labeling imaging, normalized bolus arrival time, and normalized CBF derived from single-TI arterial spin-labeling were compared in patients with World Health Organization (WHO) grade II, III, and IV astrocytomas. RESULTS: The normalized CBF value derived from multi-TI arterial spin-labeling imaging was higher in patients with higher grade astrocytoma malignancies compared with patients with lower grade astrocytomas, while the normalized bolus arrival time showed the opposite tendency. The normalized CBF value derived from the multi-TI arterial spin-labeling imaging showed excellent performance with areas under the receiver operating characteristic curve of 0.813 (WHO II versus III), 0.964 (WHO II versus IV), 0.872 (WHO III versus IV), and 0.883 (low-grade-versus-high-grade gliomas). The normalized CBF value derived from single-TI arterial spin-labeling imaging could statistically differentiate the WHO II and IV groups (area under the receiver operating characteristic curve = 0.826). The normalized bolus arrival time effectively identified the WHO grades II and III with an area under the receiver operating characteristic curve of 0.836. Combining the normalized CBF value derived from multi-TI arterial spin-labeling imaging and normalized bolus arrival time improved the diagnostic accuracy from 65.10% to 72.10% compared with the normalized CBF value derived from multi-TI arterial spin-labeling imaging being applied independently. The combination of multi-TI arterial spin-labeling imaging and conventional MR imaging had the best performance, with a diagnostic accuracy of 81.40%. CONCLUSIONS: Multi-TI arterial spin-labeling imaging can evaluate perfusion dynamics by combining normalized bolus arrival time and normalized CBF values derived from multiple TIs. It is superior to single-TI arterial spin-labeling imaging and conventional MR imaging features when applied independently and can improve the diagnostic accuracy when combined with conventional MR imaging for grading astrocytomas.

SmartArc-based volumetric modulated arc therapy can improve the middle ear, vestibule and cochlea sparing for locoregionally advanced nasopharyngeal carcinoma: a dosimetric comparison with step-and-shoot intensity-modulated radiotherapy.

OBJECTIVE: Radiation-induced sensorineural hearing loss is a common complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that significantly affects their quality of life. The goal of this study was to compare SmartArc-based volumetric modulated arc therapy (VMAT-S) with step-and-shoot intensity-modulated radiation therapy (IMRT) for patients with locoregionally advanced NPC with regard to the sparing effect on middle ear, vestibule and cochlea. METHODS: 20 patients with non-metastatic Stage III or IV NPC were selected to have planning with VMAT-S and IMRT [using Philips Pinnacle Planning System (Philips, Fitchburg, WI) for Varian accelerator] for dosimetric comparison. Mean middle ears, vestibule and cochlea doses for the two planning techniques were compared using a paired t-test. Target coverage and dose homogeneity were evaluated by calculating conformity index (CI) and homogeneity index (HI) values. RESULTS: VMAT-S had significantly improved homogeneity and conformity compared with IMRT. Mean HI of planning target volume of gross tumour volume (PGTV) was better with VMAT-S (1.05 ± 0.02) than IMRT (1.09 ± 0.03) (p < 0.001). Mean CI of PGTV is also better with VMAT-S (0.59 ± 0.12) than IMRT (0.54 ± 0.12) (p < 0.001). Mean doses to the left cochleas were 43.8 ± 3.6 and 47.8 ± 4.0 (p < 0.001) for VMAT-S and IMRT plans, respectively. Mean doses to the right cochleas were 42.7 ± 4.7 and 47.6 ± 5.4 (p < 0.001) for VMAT-S and IMRT plans, respectively. VMAT-S also significantly reduced the mean doses to middle ears (p < 0.001 for both) and vestibule (p < 0.001 for both). CONCLUSION: Our results indicate that VMAT-S provides better sparing of hearing apparatus in locoregionally advanced NPC. ADVANCES IN KNOWLEDGE: VMAT-S can improve the middle ear, vestibule and cochlea sparing in patients with locoregionally advanced NPC.

Mapping p53 mutations in low-grade glioma: a voxel-based neuroimaging analysis.

BACKGROUND AND PURPOSE: Brain tumor location has proved to be a prognostic factor that may be associated with features of neoplastic origin. Mutation of p53 is an atypical genetic change that occurs during tumorigenesis. Thus, a potential correlation may exist between tumor location and p53 status. The purpose of the current study was to identify anatomic characteristics of mutant p53 expression by using quantitative neuroimaging analyses. MATERIALS AND METHODS: Preoperative MR images from 182 patients with histologically confirmed low-grade gliomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using a voxel-based lesion-symptom mapping analysis, we located brain regions associated with a high occurrence of p53 mutation and corrected them by using a permutation test. The acquired clusters were further included as a factor in survival analyses. RESULTS: Statistical analysis demonstrated that the left medial temporal lobe and right anterior temporal lobe were specifically associated with high expression of mutant p53. Kaplan-Meier curves showed that tumors located in these regions were associated with significantly worse progression-free survival compared with tumors occurring elsewhere. CONCLUSIONS: Our voxel-level imaging analysis provides new evidence that genetic changes during cancer may have anatomic specificity. Additionally, the current study suggests that tumor location identified on structural MR images could potentially be used for customized presurgical outcome prediction.

Correlation-induced self-doping in the iron-pnictide superconductor Ba2Ti2Fe2As4O.

The electronic structure of the iron-based superconductor Ba2Ti2Fe2As4O (Tc(onset)=23.5 K) has been investigated by using angle-resolved photoemission spectroscopy and combined local density approximation and dynamical mean field theory calculations. The electronic states near the Fermi level are dominated by both the Fe 3d and Ti 3d orbitals, indicating that the spacer layers separating different FeAs layers are also metallic. By counting the enclosed volumes of the Fermi surface sheets, we observe a large self-doping effect; i.e., 0.25 electrons per unit cell are transferred from the FeAs layer to the Ti2As2O layer, leaving the FeAs layer in a hole-doped state. This exotic behavior is successfully reproduced by our dynamical mean field calculations, in which the self-doping effect is attributed to the electronic correlations in the 3d shells. Our work provides an alternative route of effective doping without element substitution for iron-based superconductors.

Sodium valproate inhibits MDA-MB-231 breast cancer cell migration by upregulating NM23H1 expression.

Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.

Absence of a holelike fermi surface for the iron-based K0.8F1.7Se2 superconductor revealed by angle-resolved photoemission spectroscopy.

We have performed an angle-resolved photoemission spectroscopy study of the new iron-based superconductor K(0.8)Fe(1.7)Se(2) (T(c)∼30 K). Clear band dispersion is observed with the overall bandwidth renormalized by a factor of 2.5 compared to our local density approximation calculations, indicating relatively strong correlation effects. Only an electronlike band crosses the Fermi energy, forming a nearly circular Fermi surface (FS) at M (π, 0). The holelike band at Γ sinks ∼90 meV below the Fermi energy, with an indirect band gap of 30 meV, to the bottom of the electronlike band. The observed FS topology in this superconductor favors (π, π) inter-FS scattering between the electronlike FSs at the M points, in sharp contrast to other iron-based superconductors which favor (π, 0) inter-FS scattering between holelike and electronlike FSs.

Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex.

The helix-loop-helix inhibitor of differentiation and DNA binding (Id1) is well known as an oncogene in various tumors. Although it has been reported that Id1 promotes several oncogenic processes, it is still unclear whether Id1 functions through epigenetic transcriptional regulation. In this study, we examined the effect of Id1 on polycomb group (PcG) proteins, which are crucial epigenetic gene silencers, and found that Id1 regulated the expression of Mel-18 and Bmi-1, both of which belong to polycomb repressive complex 1. We also confirmed that Id1 induced Mel-18 downregulation, which was mediated by the Akt pathway, and consequently upregulated the transcription of its target gene, c-Myc. Using a promoter-reporter, we demonstrated that Id1 regulated Bmi-1 transcription through c-Myc binding to its E-box in the promoter. Finally, we examined the activity of E3 ligase RING1b, whose catalytic activity is increased by binding with the RING finger protein Bmi-1, and found that Id1 overexpression enhanced RING1b E3 ligase activity leading to accumulation of H2A ubiquitination and ubiquitin/proteasome-mediated degradation of geminin. Taken together, our study provided a novel link between Id1 and PcG proteins and suggested that Id1 may contribute to tumor development through PcG-mediated epigenetic regulation.

Angle-resolved photoemission spectroscopy of the iron-chalcogenide superconductor Fe1.03Te0.7Se0.3: strong coupling behavior and the universality of interband scattering.

We have performed angle-resolved photoemission spectroscopy of the iron-chalcogenide superconductor Fe1.03Te0.7Se0.3 to investigate the electronic structure relevant to superconductivity. We observed a holelike Fermi surface (FS) and an electronlike FS at the Brillouin zone center and corner, respectively, which are nearly nested by the Q∼(π,π) wave vector. We do not find evidence for the nesting instability with Q∼(π+δ,0) reminiscent of the antiferromagnetic order in the parent compound Fe1+yTe. We have observed an isotropic superconducting (SC) gap along the holelike FS with the gap size Δ of ∼4 meV (2Δ/kBTc ∼ 7), demonstrating the strong-coupling superconductivity. The observed similarity of low-energy electronic excitations between iron-chalcogenides and iron-arsenides strongly suggests that common interactions which involve Q∼(π,π) scattering are responsible for the SC pairing.

Id-1 activates Akt-mediated Wnt signaling and p27(Kip1) phosphorylation through PTEN inhibition.

Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3beta phosphorylation at Ser9, stabilization and nuclear localization of beta-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27(Kip1) phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27(Kip1) phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Although Bracken et al have demonstrated a significant neuroprotective effect of high-dose intravenous (i.v.) methylprednisolone (MP) within 8 h post spinal cord injury (SCI), this practice has recently been challenged. We hypothesized it is possible that acute corticosteroid myopathy (ACM) may occur secondary to the MP. This pilot study was performed to test this hypothesis. SETTING: University of Miami School of Medicine/Jackson Memorial Hospital, Miami VA Medical Center, FL, USA. METHODS: Subjects included five nonpenetrating traumatic SCI patients, who received 24 h MP according to National Acute Spinal Cord Injury Studies (NASCIS) protocol, and three traumatic patients who suffered SCI and did not receive MP. Muscle biopsies and electromyography (EMG) were performed to determine if myopathic changes existed in these patients. RESULTS: Muscle biopsies from the SCI patients who received 24 h of MP showed muscle damage consistent with ACM in four out of five cases. EMG studies demonstrated myopathic changes in the MP-treated patients. In the three patients who had SCI but did not receive MP, muscle biopsies were normal and EMGs did not reveal evidence of myopathy. CONCLUSION: Our data suggest that MP in the dose recommended by the NASCIS may cause ACM. If this is true, part of the improvement of neurological recovery showed in NASCIS may be only a recording of the natural recovery of ACM, instead of any protection that MP offers to the injured spinal cord.

NF-kappaB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis.

BACKGROUND AND AIMS: Hepatocyte apoptosis is induced by tumor necrosis factor alpha (TNF-alpha) and Fas ligand. Although nuclear factor-kappaB (NF-kappaB) activation protects hepatocytes from TNF-alpha-mediated apoptosis, the NF-kappaB responsive genes that protect hepatocytes are unknown. Our aim was to study the role of NF-kappaB activation and inducible nitric oxide synthases (iNOSs) in TNF-alpha- and Fas-mediated apoptosis in hepatocytes. METHODS: Primary cultures of hepatocytes from wild-type and iNOS knockout mice were treated with TNF-alpha, the Fas agonistic antibody Jo2, a nitric oxide (NO) donor (S-nitroso-N-acetylpenicillamine), an NO inhibitor (N(G)-methyl-L-arginine acetate), and/or adenovirus-expressing NF-kappaB inhibitors. RESULTS: The IkappaB superrepressor and a dominant-negative form of IkappaB kinase beta (IKKbeta) inhibited NF-kappaB binding activity by TNF-alpha or Jo2 and sensitized hepatocytes to TNF-alpha- and Jo2-mediated apoptosis. TNF-alpha and Jo2 induced iNOS messenger RNA and protein levels through the induction of NF-kappaB. S-nitroso-N-acetylpenicillamine inhibited Bid cleavage, the mitochondrial permeability transition, cytochrome c release, and caspase-8 and -3 activity, and reduced TNF-alpha- and Fas-mediated death in hepatocytes expressing IkappaB superrepressor. N(G)-methyl-L-arginine acetate partially sensitized hepatocytes to TNF-alpha- and Fas-mediated cell killing. TNF-alpha alone or Jo2 alone induced moderate cell death in hepatocytes from iNOS(-)/(-) mice. CONCLUSIONS: NO protects hepatocytes from TNF-alpha- and Fas-mediated apoptosis. Endogenous iNOS, which is activated by NF-kappaB via IKKbeta, provides partial protection from apoptosis.