Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas

BACKGROUND: Oligodendroglioma (ODG) and oligoastrocytoma (OAC) are diffusely infiltrating primary brain tumors whose pathogenesis remains unclear. We previously identified a group of genes whose expression was inversely correlated with survival in a cohort of patients with glioblastoma (GBM), and some of these genes are also reportedly expressed in ODG and OAC. We examined the expression patterns and localization of these survival-associated genes in ODG and OAC in order to analyze their possible roles in the oncogenesis of these two tumor types. METHODS: We used UniGene libraries derived from GBM and ODG specimens to examine the expression levels of the transcripts for each of the 50 GBM survival-associated genes. We used immunohistochemistry and cDNA microarrays to examine expression of selected survival-associated genes and Id4, a gene believed to control the timing of oligodendrocyte development. The expression of FABP7 and Id4 and the survival of patients with ODG and OAC were also analyzed. RESULTS: Transcripts of most survival-associated genes as well as Id4 were present in both GBM and ODG tumors, whereas protein expression of Id4 and one of the survival-associated genes, brain-type fatty acid-binding protein (FABP7), was present in cells with astrocytic features, including reactive and neoplastic astrocytes, but not in neoplastic oligodendrocytes. Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC. Id4 and FABP7 expression, however, did not correlate with the clinical outcome of patients with ODG or OAC tumors. CONCLUSION: Expression of Id4 and some of our previously identified GBM survival-associated genes is present in developing or mature oligodendrocytes. However, protein expression of Id4 and FABP7 in GBM, ODG, and OAC suggests that this group of functionally important genes might demonstrate two patterns of expression in these glioma subtypes: one group is universally expressed in glioma cells, and the other group of genes is expressed primarily in neoplastic astrocytes but not in neoplastic oligodendrocytes. Differential protein expression of these two groups of genes in ODG and OAC may be related to the cellular origins and the histological features of the neoplastic cells

Probe R-parity violating stop resonance at the LHeC

We investigate the possibility of detecting single sqaurk production at the proposed LHeC collider, in the framework of R-parity violating supersymmetry. Taking advantage of the enhancement of the direct resonance production of squark and the distinctive kinematics distributions of $\tilde{q}\rightarrow l q$ two body decay final states, the LHeC provides excellent opportunities of probing R-violating $\hat{L}\hat{Q}\hat{D}$ interactions at unprecedented level compared to all the knowledge derived from indirect low energy nucleon measurements. If no apparent deviation from SM predictions on high invariant mass of muon and b-quark final states at the LHeC with 1$fb^{-1}$ data, the sensitivities on $\hat{L}\hat{Q}\hat{D}$ coupling constant $\lambda^{'}_{131} \times \lambda^{'}_{233}$ can be improved by nearly four orders, at energy scale about 100 GeV.Comment: 9 pages, 8 figure

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

High levels of Nesfatin-1 in relation to the dysfunction of the hypothalamic–pituitary–adrenal and hypothalamus–pituitary–thyroid axes in depressed patients with subclinical hypothyroidism

Ya-Yun Xu,1,2 Jun Liang,1,2 Yin Cao,1,2 Feng Shan,1,2 Yang Liu,1,2 Qing-Rong Xia1,2 1Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 2Anhui Mental Health Center, Hefei, People’s Republic of China Abstract: Despite the increasing amount of evidence suggesting a relationship between depression and subclinical hypothyroidism (SCH), the exact mechanism underlying this relationship remains unclear. The main purpose of this study was to investigate the roles of plasma Nesfatin-1 levels and dysfunction of the hypothalamic–pituitary–adrenal (HPA) and hypothalamus–pituitary–thyroid (HPT) axes in the comorbidity of depression and SCH. Dysfunctions of the HPA and HPT axes were detected by measuring plasma corticosterone and thyroid-stimulating hormone (TSH) concentrations, respectively. Subjects in the patient group were selected from patients hospitalized at the Anhui Mental Health Center, and subjects in the control group were recruited from healthy volunteers. Healthy control subjects were matched to the patients in terms of weight and body mass index. The Hamilton Depression Rating Scale was administered to both the groups. The enzyme-linked immunosorbent assay method was used to measure plasma Nesfatin-1, corticosterone, and TSH levels. A radioimmunoassay kit was used for the measurement of the plasma-free triiodothyronine and plasma-free thyroxine. The results showed that the Hamilton Depression Rating Scale scores and average Nesfatin-1, corticosterone, and TSH levels were significantly higher in depressed patients with SCH than in the control group. Moreover, positive relationships were observed between Nesfatin-1 levels and the concentrations of corticosterone (r=0.626, P<0.001) and TSH (r=0.229, P=0.036) in depressed patients with SCH. These findings indicate that Nesfatin-1 is involved in the comorbidity of depression and SCH, and the mechanism underlying this involvement might be related to the dysfunction of the HPA and HPT axes. Keywords: corticosterone, depression, HPA axis, HPT axis, TSH, SCH &nbsp

Nesfatin-1 and cortisol: potential novel diagnostic biomarkers in moderate and severe depressive disorder

Ya-Yun Xu,1,2 Jin-Fang Ge,3 Jun Liang,1,2 Yin Cao,1,2 Feng Shan,1,2 Yang Liu,1,2 Chun-Yu Yan,1,2 Qing-Rong Xia1,2 1Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei 230022, China; 2Psychopharmacology Laboratory, Anhui Mental Health Center, Hefei 230032, China; 3Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China Background: This study aimed to determine whether plasma nesfatin-1, cortisol, and inflammatory cytokines could be used as novel noninvasive biomarkers for the diagnosis of moderate and severe depressive disorder (MSDD). Materials and methods: A total of 70 patients with MSDD and 70 healthy subjects were assessed. Patients with MSDD were selected from Hefei Fourth People’s Hospital, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Hamilton Depression Rating Scale-17 (HAMD-17) was used to evaluate the two groups. ELISA was used for the measurement of plasma nesfatin-1, cortisol, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. The diagnostic value of plasma nesfatin-1, cortisol, IL-6, CRP, and TNF-α for MSDD was assessed. Results: Compared to healthy controls, the HAMD-17 scores and average nesfatin-1, cortisol, IL-6, and CRP levels in patients with MSDD were significantly increased. Moreover, multivariate linear regression analysis showed that HAMD-17 score was positively associated with plasma nesfatin-1 and cortisol. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.985 with 94.3% sensitivity and 97.1% specificity of nesfatin-1, and an AUC of 0.957 with 91.4% sensitivity and 85.7% specificity of cortisol in discriminating patients with MSDD from healthy volunteers. A combined ROC analysis using nesfatin-1 and cortisol revealed an AUC of 0.993 with a sensitivity of 97.1% and a specificity of 98.6% in separating patients with MSDD from healthy volunteers. Conclusion: These results suggest that plasma nesfatin-1 and cortisol might be potential novel biomarkers for the diagnosis of MSDD. Keywords: C-reactive protein, cortisol, IL-6, depression, nesfatin-1, tumor necrosis factor-&alpha